Request History

• Restore to current request
• applications/view/1197
• applications/index/page:97/sort:study_title/direction:desc/approved:2
• applications/index/page:96/sort:study_title/direction:asc/approved:1
• applications/index/page:82/sort:protocol_no/direction:desc

Session

• Config(array)
  • userAgent9c3d2c89526db53b7b69e8c9faa06145
  • time1746171733
  • countdown10

Request

Cake Params

• plugin(null)
• controllerapplications
• actionindex
• named(array)
  • page78
  • sortstudy_title
  • directiondesc
• pass(empty)
• isAjax(false)
• paging(array)
  • Application(array)
    • page78
    • current5
    • count502
    • prevPage(true)
    • nextPage(true)
    • pageCount101
    • order(array)
      • Application.study_titledesc
    • limit5
    • options(array)
      • page78
      • order(array)
        • Application.study_titledesc
      • sortstudy_title
      • directiondesc
    • paramTypenamed

Post data

• Application(empty)

Query string

No querystring data.

Cookie

To view Cookies, add CookieComponent to Controller

Current Route

• keys(array)
  • 0controller
  • 1action
• options(empty)
• defaults(array)
  • plugin(null)
• template/:controller/:action/*

Sql Logs

Logs

View Variables

• trial_statuses(array)
  • 1Recruiting
  • 2Not yet recruiting
  • 3Suspended
  • 4Stopped
  • 5Completed
  • 6In follow-up
  • 7Analysing
  • 8Writing-up
  • 9Application withdrawn
• applications(array)
  • 0(array)
    • Application(array)
      • id1145
      • user_id613
      • trial_status_id6
      • abstract_of_study<p>\n Shigellosis remains a major public health problem around the world; it is one of the leading causes of diarrheal disease in low- and middle-income countries (LMIC), particularly in young children. The Global Burden of Disease study (IHME) estimated that in 2017 Shigella caused approximately 238,000 deaths globally and, with 15.2%, it ranked second with regard to pathogen contributions in global diarrheal deaths. In infants, in LMIC, particularly where healthcare resources are limited, shigellosis can often lead to death.  There is presently no widely available vaccine against Shigella. Treatment for shigellosis is mainly supportive to keep patients stable and restore lost electrolytes due to diarrhea. If available, specific antibiotics are sometimes used for severe cases of shigellosis.</p>\n<p>\n Current drugs are under threat from the increasing rates of antibiotic resistance in Shigella serotypes around the world. Prevention of diarrheal diseases caused by Shigella, with the introduction of an efficacious vaccine is important. This is a Phase 1/2 observer-blind, controlled, self-contained, randomised, multi-country, staged, age-de-escalation study. This study will evaluate the safety and immunogenicity of a new candidate Shigella 4-component generalized modules for membrane antigens (GMMA), the altSonflex1-2-3 GMMA vaccine against S. sonnei and S. flexneri serotypes 1b, 2a, and 3a and select the dose of administration for further clinical development in the target population of infants. The candidate altSonflex1-2-3 vaccine will be administered intramuscularly first in adults 18 to 50 years in Europe (Stage 1) and, subsequently in stage 2, to adults 18 to 50 years, children 24 to 59 months, and 9 months old infants in Kericho, Kenya using three different doses of vaccine (A [low], B[medium], and C [high]). In stage 2, participants will be randomized to receive either altSonflex1-2-3 GMMA vaccine or control vaccine. The adults will receive 2 vaccinations of altSonflex1-2-3 GMMA vaccine three months apart or menveo and boostrix 3 months apart. The children will receive 2 vaccinations of altSonflex1-2-3 GMMA vaccine 3 months apart or menveo and typhim Vi 3 months apart. The infants will receive 2 vaccinations of altSonflex1-2-3 GMMA vaccine 3 months apart and a third vaccine 6 months after the 2^nd vaccination or menveo 3 months apart and infanrix 6 months after the 2^nd vaccination. A total of 448 (20 adults, 40 children, 388 infants) participants who meet the eligibility criteria as described in the main protocol will be enrolled at Kericho. Adults and children will be followed up for 4 months while infants will be followed up for 11 months. The results of this study will allow the selection of the most appropriate dose for further vaccine development in infants 9 months of age, which is the main target age group for this vaccine. The study findings will be shared with all authorities having oversight of this protocol including the sponsor, Kenya Medical Research Institute Scientific Ethics Review Unit, Pharmacy and Poisons Board, Walter Reed Army Institute of Research Institutional Review Board and Kenya’s Ministry of Health.</p>\n<p>\n  </p>\n
      • study_title<p align=\"center\">\n A staged Phase I/II observer-blind, randomised, controlled, multi-country study to evaluate the safety, reactogenicity, and immune responses to the GVGH altSonflex1-2-3 vaccine against <em>S. sonnei</em> and <em>S. flexneri,</em> serotypes 1b, 2a, and 3a, in adults in Europe (Stage 1) followed by age de-escalation from adults to children and infants, and dose-finding in infants in Africa (Stage 2)</p>\n<p align=\"center\">\n  </p>\n<p>\n  </p>\n
      • laymans_summary<p>\n Shigellosis is an infectious disease caused by a group of bacteria called Shigella. Shigellosis remains a major public health problem around the world; it is one of the leading causes of diarrheal disease in low- and middle-income countries (LMIC), particularly in young children. The Global Burden of Disease study (IHME) estimated that in 2017 Shigella caused approximately 238,000 deaths globally. In infants, in LMIC, particularly where healthcare resources are limited, shigellosis can often lead to death.  There is presently no widely available vaccine against Shigella. Treatment for shigellosis is mainly supportive to keep patients stable. Shigellosis can be treated with antibiotics but many Shigella bacteria no longer respond well to or are resistant to most of the used antibiotics. Thus, a very important way to fight Shigella is through prevention with the use of vaccination.. The aim of the study is to assess how an experimental Shigella vaccine, called altSonflex1-2-3 makes the body to produce proteins that fight off the bacteria causing shigellosis and to assess the side effects the vaccine may cause. The study is being conducted in two stages. Stage 1 in Europe and stage 2 in Kericho, Kenya. In Kericho, If the vaccine is found to be safe for adults, 18-50 years old, the study will progress to include children, 24 to 59 months and then 9 months old infants who will receive one of three different dose levels of the vaccine (A [low], B[medium], and C [high]). The adults will receive either 2 injections of the Shigella vaccine or 2 injections of a control vaccine, the first with Menveo (a vaccine that prevents meningitis) followed by boostrix (a vaccine that prevents tetanus, diphtheria and whooping cough). The children will receive either 2 injections of Shigella vaccine or 2 injections of control vaccines, the first one being Menveo followed by Typhim VI (a vaccine that prevents typhoid fever) as the second one. The infants will receive either 3 injections of Shigella vaccine or 2 injections of Menveo followed by 1 injection of Infanrix (a vaccine for children that prevents diphtheria, tetanus and whooping cough). Adults and children will be followed up for 4 months while infants will be followed up for 11 months. The benefits of this study include, participants or participants’ parents may gain medical advice about their own or their children’s health status through the medical evaluations and laboratory assessments associated with the study. Vaccines administered as control and not routinely given will be provided free of charge and can provide protection against meningitis, typhoid, diphtheria, tetanus, pertussis. The children and infants who will be assigned to receive the shigella vaccine will receive menveo vaccine after the study is completed as a benefit. The results of this study will allow the selection of the most appropriate dose for further vaccine development in infants 9 months of age, which is the main target age group for this vaccine.</p>\n
      • short_titleProtocol H06_01TP
      • protocol_noECCT/22/08/04
      • version_no2
      • date_of_protocol14-02-2022
      • study_drugaltSonflex1-2-3
      • disease_conditionShigella
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressKericho.DRS@usamru-k.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantDeborah Chepngeno Langat
      • declaration_date124-08-2022
      • declaration_principal_investigatorDeborah Chepngeno Langat
      • declaration_date224-08-2022
      • placebo_presentNo
      • study_objectives<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:660px;\" width=\"990\">\n <tbody>\n <tr>\n <td style=\"width:222px;\">\n <p>\n <strong>Objectives</strong></p>\n </td>\n <td style=\"width:438px;\">\n <p>\n <strong>Endpoints</strong></p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:660px;\">\n <p align=\"center\">\n <strong>Primary</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:222px;\">\n <ul>\n <li>\n To identify the preferred dose of each component of the altSonflex1-2-3 vaccine (low, medium, or high) for infants 9 months of age in Africa (Stage 2).</li>\n </ul>\n <p style=\"margin-left:12.5pt;\">\n  </p>\n </td>\n <td style=\"width:438px;\">\n <ul>\n <li>\n Anti-serotype specific Shigella lipopolysaccharide (LPS)* serum immunoglobulin G (IgG) titres as measured by reference enzymelinked immunosorbent assay (ELISA), in infants 9 months of age in Africa, 28 days after the third vaccination (Day 281).</li>\n </ul>\n <p>\n *S. sonnei, S. flexneri 1b, S. flexneri 2a, and S. flexneri 3a serotypes will be tested.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:222px;\">\n <ul>\n <li>\n To evaluate the safety and reactogenicity of the altSonflex1-2-3 vaccine in all participants in Africa (Stage 2).</li>\n </ul>\n </td>\n <td style=\"width:438px;\">\n <ul>\n <li>\n Number of adults 18 to 50 years of age in Africa with solicited administration-site events during 7 days after each vaccination (study intervention administered on Day 1 and Day 85).</li>\n <li>\n Number of adults 18 to 50 years of age in Africa with solicited systemic events during 7 days after each vaccination (study intervention administered on Day 1 and Day 85).</li>\n <li>\n Number of adults 18 to 50 years of age in Africa with unsolicited AEs during 28 days after each vaccination (study intervention administered on Day 1 and Day 85).</li>\n <li>\n Number of adults 18 to 50 years of age in Africa with SAEs during their entire study participation period (from Day 1 to Day 113).</li>\n <li>\n Number of adults 18 to 50 years of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results, at 7 days after each vaccination (Day 8 and Day 92).</li>\n <li>\n Number of children 24 to 59 months of age in Africa with solicited administration-site events during 7 days after each vaccination (study intervention administered on Day 1 and Day 85).</li>\n <li>\n Number of children 24 to 59 months of age in Africa with solicited systemic events during 7 days after each vaccination (study intervention administered on Day 1 and Day 85).</li>\n <li>\n Number of children 24 to 59 months of age in Africa with unsolicited AEs during 28 days after each vaccination (study intervention administered on Day 1 and Day 85).</li>\n <li>\n Number of children 24 to 59 months of age in Africa with SAEs during their entire study participation period (from Day 1 to Day 113).</li>\n <li>\n Number of children 24 to 59 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results, at 7 days after each vaccination (Day 8 and Day 92).</li>\n <li>\n Number of infants 9 months of age in Africa with solicited administration-site events during 7 days after each vaccination (study intervention administered on Day 1, Day 85, and Day 253).</li>\n <li>\n Number of infants 9 months of age in Africa with solicited systemic events during 7 days after each vaccination (study intervention administered on Day 1, Day 85, and Day 253).</li>\n <li>\n Number of infants 9 months of age in Africa with unsolicited AEs during 28 days after each vaccination (study intervention administered on Day 1, Day 85, and Day 253).</li>\n <li>\n Number of infants 9 months of age in Africa with SAEs during their entire study participation period (from Day 1 to Day 281).</li>\n <li>\n Number of infants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results, at 7 days after each vaccination (Day 8, Day 92, and Day 260).</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:660px;\">\n <p align=\"center\">\n <strong>Secondary</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:222px;\">\n <ul>\n <li>\n  </li>\n </ul>\n </td>\n <td style=\"width:438px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:222px;\">\n <ul>\n <li>\n To evaluate the immunogenicity profile of the altSonflex1-2-3 vaccine in all participants in Africa (Stage 2).</li>\n </ul>\n </td>\n <td style=\"width:438px;\">\n <ul>\n <li>\n Anti-serotype specific Shigella LPS* serum IgG geometric mean titres (GMTs), in adults 18 to 50 years of age in Africa, as measured by reference ELISA, before each vaccination (Day 1 and Day 85) and 28 days after each vaccination (Day 29 and Day 113).</li>\n <li>\n Anti- serotype specific Shigella LPS* serum IgG GMTs, in children 24 to 59 months of age in Africa, as measured by reference ELISA, before each vaccination (Day 1 and Day 85) and 28 days after each vaccination (Day 29 and Day 113).</li>\n <li>\n Anti-serotype specific Shigella LPS* serum IgG GMTs, in infants 9 months of age in Africa, as measured by reference ELISA, before each vaccination (Day 1, Day 85, and Day 253) and 28 days after each vaccination (Day 29, Day 113, and Day 281).</li>\n </ul>\n <p style=\"margin-left:.25in;\">\n *S. sonnei, S. flexneri 1b, S. flexneri 2a, and S. flexneri 3a serotypes will be tested.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:222px;\">\n <ul>\n <li>\n To further characterise the immunogenicity profile of the S. sonnei component of altSonflex1-2-3 vaccine in all participants in Africa (Stage 2).</li>\n </ul>\n </td>\n <td style=\"width:438px;\">\n <ul>\n <li>\n Number of adults in Africa 18 to 50 years of age achieving a reference ELISA level equivalent to ≥1:800* titre against S. sonnei LPS, before each vaccination (Day 1 and Day 85) and 28 days after each vaccination (Day 29 and Day 113).</li>\n <li>\n Number of children 24 to 59 months of age in Africa achieving a reference ELISA level equivalent to ≥1:800* titre against S. sonnei LPS in, before each vaccination (Day 1 and Day 85) and 28 days after each vaccination (Day 29 and Day 113).</li>\n <li>\n Number of infants 9 months of age in Africa achieving a reference ELISA level equivalent to ≥1:800* titre against S. sonnei LPS, before each vaccination (Day 1, Day 85, and Day 253) and 28 days after each vaccination (Day 29, Day 113, and Day 281).</li>\n <li>\n Number of adults in Africa 18 to 50 years of age achieving a reference ELISA level equivalent to ≥1:1600** titre against S. sonnei LPS, before each vaccination (Day 1 and Day 85) and 28 days after each vaccination (Day 29 and Day 113).</li>\n <li>\n Number of children 24 to 59 months of age in Africa achieving a reference ELISA level equivalent to ≥1:1600** titre against S. sonnei LPS in, before each vaccination (Day 1 and Day 85) and 28 days after each vaccination (Day 29 and Day 113).</li>\n <li>\n Number of infants 9 months of age in Africa achieving a reference ELISA level equivalent to ≥1:1600** titre against S. sonnei LPS, before each vaccination (Day 1, Day 85, and Day 253) and 28 days after each vaccination (Day 29, Day 113, and Day 281).</li>\n </ul>\n <p>\n *This threshold (1:800, known as “Cohen’s Threshold”) has been previously reported to be potentially protective for Shigella [Cohen, 1988; Launay, 2017] and will be calibrated for the assay to be used in this study. The details of the equivalent threshold to be used will be reported in the Clinical Study Report (CSR).</p>\n <p>\n **This threshold (1:1600, double of “Cohen’s Threshold”) will be calibrated for the assay to be used in this study. The details of the equivalent threshold to be used will be reported in the CSR.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:222px;\">\n <ul>\n <li>\n To evaluate  seroresponse with the altSonflex1-2-3 vaccine after each vaccination in all participants in Africa (Stage 2).</li>\n </ul>\n </td>\n <td style=\"width:438px;\">\n <ul>\n <li>\n Number of adults 18 to 50 years of age in Africa showing at least a 4-fold increase in anti-serotype specific Shigella LPS* serum IgG titres, as measured by reference ELISA, at 28 days after each vaccination (Day 29 and Day 113), compared to baseline (Day 1 and Day 85).</li>\n <li>\n Number of children 24 to 59 months of age showing at least a 4-fold increase in anti-serotype specific Shigella LPS* serum IgG titres, as measured by reference ELISA, at 28 days after each vaccination (Day 29 and Day 113), compared to baseline (Day 1 and Day 85).</li>\n <li>\n Number of infants 9 months of age showing at least a 4-fold increase in anti-serotype specific Shigella LPS* serum IgG titres, as measured by reference ELISA, at 28 days after each vaccination (Day 29, Day 113, and Day 281), compared to baseline (Day 1, Day 85, and Day 253).</li>\n </ul>\n <p>\n *S. sonnei, S. flexneri 1b, S. flexneri 2a, and S. flexneri 3a serotypes will be tested</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:222px;\">\n <ul>\n <li>\n To evaluate the immunogenicity of co-administered MR-VAC in infants 9 months of age in Africa (Stage 2), in the dose-finding cohort.</li>\n </ul>\n </td>\n <td style=\"width:438px;\">\n <ul>\n <li>\n Anti-measles IgG concentrations, as measured by ELISA, in infants 9 months of age in Africa, in the dose-finding cohort, before the first MR-VAC (Day 1) and at 28 days after the second MR-VAC vaccination (Day 281).</li>\n <li>\n Anti-rubella IgG concentrations, as measured by ELISA, in infants 9 months of age in Africa, in the dose-finding cohort, before the first MR-VAC (Day 1) and at 28 days after the second MR-VAC vaccination (Day 281).</li>\n <li>\n Number of infants 9 months of age, in the dose-finding cohort, achieving anti-measles IgG concentrations of ≥150 mIU/mL* and ≥ 200 mIU/mL*, as measured by ELISA, at 28 days after the second MR-VAC vaccination (Day 281).</li>\n <li>\n Number of infants 9 months of age, in the dose-finding cohort, achieving anti-rubella IgG concentrations of ≥4 IU/mL* and ≥10 IU/mL*, as measured by ELISA, at 28 days after the second MR-VAC vaccination (Day 281).</li>\n </ul>\n <p>\n *This threshold is based on the vaccine correlate of protection and World Health Organization guidelines.</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:660px;\">\n <p align=\"center\">\n <strong>Tertiary</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:222px;\">\n <ul>\n <li>\n To evaluate the immune response induced by the Sonflex1-2-3 vaccine in 25% of infants 9 months of age in Africa (Stage 2), in the dose-finding cohort, using the serum bactericidal assay (SBA).</li>\n </ul>\n </td>\n <td style=\"width:438px;\">\n <ul>\n <li>\n Anti-serotype specific* serum bactericidal antibody GMTs in 25% of infants 9 months of age in the dose-finding cohort, before each vaccination (Day 1, Day 85, and Day 253) and 28 days after each vaccination (Day 29, Day 113, and Day 281).</li>\n </ul>\n <p>\n *S. sonnei, S. flexneri 1b, S. flexneri 2a, and S. flexneri 3a serotypes will be tested.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:222px;\">\n <ul>\n <li>\n To further explore immune responses to the altSonflex1-2-3 vaccine in 25% of adults in Europe (Stage 1) and 25% of infants 9 months of age in Africa (Stage 2), in the dose finding</li>\n </ul>\n <p>\n cohort.</p>\n </td>\n <td style=\"width:438px;\">\n <ul>\n <li>\n Antibody features (subclassing, affinity, avidity) and functional properties (induction of cellular phagocytosis and cellular cytotoxicity, natural killer [NK] cell activation, eosinophil and basophil degranulation, complement deposition, neutrophil activation/ phagocytosis, dendritic cell phagocytosis, mucin binding, glycosylation, and Fc receptor alteration), as measured by systems serology analysis</li>\n <li>\n Anti-serotype serum bactericidal antibody GMTs against a panel of vaccine heterologous Shigella serotypes, as measured by SBA</li>\n <li>\n Anti-serotype serum bactericidal antibody GMTs against a panel of vaccine homologous and heterologous Shigella serotypes, as measured by opsonophagocytosis assay</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n Healthy participants as established by medical history, and clinical examination, and laboratory assessment</p>\n
      • principal_exclusion_criteria<p>\n Known exposure to Shigella during lifetime of the participant as confirmed during interview with the participant or documented by patient records (e.g., history of microbiologically-confirmed Shigella infection), recent travel* (within 2 years) to a country where Shigella or other enteric infections are endemic, or recent occupation* (within 3 years) involving Shigella species.</p>\n<p>\n  </p>\n
      • primary_end_points<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width: 660px;\" width=\"990\">\n <tbody>\n <tr>\n <td style=\"width: 222px;\">\n <p>\n <strong>Objectives</strong></p>\n </td>\n <td style=\"width: 438px;\">\n <p>\n <strong>Endpoints</strong></p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width: 660px;\">\n <p align=\"center\">\n <strong>Primary</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 222px;\">\n <ul>\n <li>\n To identify the preferred dose of each component of the altSonflex1-2-3 vaccine (low, medium, or high) for infants 9 months of age in Africa (Stage 2).</li>\n </ul>\n <p style=\"margin-left: 12.5pt;\">\n  </p>\n </td>\n <td style=\"width: 438px;\">\n <ul>\n <li>\n Anti-serotype specific Shigella lipopolysaccharide (LPS)* serum immunoglobulin G (IgG) titres as measured by reference enzymelinked immunosorbent assay (ELISA), in infants 9 months of age in Africa, 28 days after the third vaccination (Day 281).</li>\n </ul>\n <p>\n *S. sonnei, S. flexneri 1b, S. flexneri 2a, and S. flexneri 3a serotypes will be tested.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 222px;\">\n <ul>\n <li>\n To evaluate the safety and reactogenicity of the altSonflex1-2-3 vaccine in all participants in Africa (Stage 2).</li>\n </ul>\n </td>\n <td style=\"width: 438px;\">\n <ul>\n <li>\n Number of adults 18 to 50 years of age in Africa with solicited administration-site events during 7 days after each vaccination (study intervention administered on Day 1 and Day 85).</li>\n <li>\n Number of adults 18 to 50 years of age in Africa with solicited systemic events during 7 days after each vaccination (study intervention administered on Day 1 and Day 85).</li>\n <li>\n Number of adults 18 to 50 years of age in Africa with unsolicited AEs during 28 days after each vaccination (study intervention administered on Day 1 and Day 85).</li>\n <li>\n Number of adults 18 to 50 years of age in Africa with SAEs during their entire study participation period (from Day 1 to Day 113).</li>\n <li>\n Number of adults 18 to 50 years of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results, at 7 days after each vaccination (Day 8 and Day 92).</li>\n <li>\n Number of children 24 to 59 months of age in Africa with solicited administration-site events during 7 days after each vaccination (study intervention administered on Day 1 and Day 85).</li>\n <li>\n Number of children 24 to 59 months of age in Africa with solicited systemic events during 7 days after each vaccination (study intervention administered on Day 1 and Day 85).</li>\n <li>\n Number of children 24 to 59 months of age in Africa with unsolicited AEs during 28 days after each vaccination (study intervention administered on Day 1 and Day 85).</li>\n <li>\n Number of children 24 to 59 months of age in Africa with SAEs during their entire study participation period (from Day 1 to Day 113).</li>\n <li>\n Number of children 24 to 59 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results, at 7 days after each vaccination (Day 8 and Day 92).</li>\n <li>\n Number of infants 9 months of age in Africa with solicited administration-site events during 7 days after each vaccination (study intervention administered on Day 1, Day 85, and Day 253).</li>\n <li>\n Number of infants 9 months of age in Africa with solicited systemic events during 7 days after each vaccination (study intervention administered on Day 1, Day 85, and Day 253).</li>\n <li>\n Number of infants 9 months of age in Africa with unsolicited AEs during 28 days after each vaccination (study intervention administered on Day 1, Day 85, and Day 253).</li>\n <li>\n Number of infants 9 months of age in Africa with SAEs during their entire study participation period (from Day 1 to Day 281).</li>\n <li>\n Number of infants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results, at 7 days after each vaccination (Day 8, Day 92, and Day 260).</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width: 660px;\">\n <p align=\"center\">\n <strong>Secondary</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 222px;\">\n <ul>\n <li>\n  </li>\n </ul>\n </td>\n <td style=\"width: 438px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 222px;\">\n <ul>\n <li>\n To evaluate the immunogenicity profile of the altSonflex1-2-3 vaccine in all participants in Africa (Stage 2).</li>\n </ul>\n </td>\n <td style=\"width: 438px;\">\n <ul>\n <li>\n Anti-serotype specific Shigella LPS* serum IgG geometric mean titres (GMTs), in adults 18 to 50 years of age in Africa, as measured by reference ELISA, before each vaccination (Day 1 and Day 85) and 28 days after each vaccination (Day 29 and Day 113).</li>\n <li>\n Anti- serotype specific Shigella LPS* serum IgG GMTs, in children 24 to 59 months of age in Africa, as measured by reference ELISA, before each vaccination (Day 1 and Day 85) and 28 days after each vaccination (Day 29 and Day 113).</li>\n <li>\n Anti-serotype specific Shigella LPS* serum IgG GMTs, in infants 9 months of age in Africa, as measured by reference ELISA, before each vaccination (Day 1, Day 85, and Day 253) and 28 days after each vaccination (Day 29, Day 113, and Day 281).</li>\n </ul>\n <p style=\"margin-left: 0.25in;\">\n *S. sonnei, S. flexneri 1b, S. flexneri 2a, and S. flexneri 3a serotypes will be tested.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 222px;\">\n <ul>\n <li>\n To further characterise the immunogenicity profile of the S. sonnei component of altSonflex1-2-3 vaccine in all participants in Africa (Stage 2).</li>\n </ul>\n </td>\n <td style=\"width: 438px;\">\n <ul>\n <li>\n Number of adults in Africa 18 to 50 years of age achieving a reference ELISA level equivalent to ≥1:800* titre against S. sonnei LPS, before each vaccination (Day 1 and Day 85) and 28 days after each vaccination (Day 29 and Day 113).</li>\n <li>\n Number of children 24 to 59 months of age in Africa achieving a reference ELISA level equivalent to ≥1:800* titre against S. sonnei LPS in, before each vaccination (Day 1 and Day 85) and 28 days after each vaccination (Day 29 and Day 113).</li>\n <li>\n Number of infants 9 months of age in Africa achieving a reference ELISA level equivalent to ≥1:800* titre against S. sonnei LPS, before each vaccination (Day 1, Day 85, and Day 253) and 28 days after each vaccination (Day 29, Day 113, and Day 281).</li>\n <li>\n Number of adults in Africa 18 to 50 years of age achieving a reference ELISA level equivalent to ≥1:1600** titre against S. sonnei LPS, before each vaccination (Day 1 and Day 85) and 28 days after each vaccination (Day 29 and Day 113).</li>\n <li>\n Number of children 24 to 59 months of age in Africa achieving a reference ELISA level equivalent to ≥1:1600** titre against S. sonnei LPS in, before each vaccination (Day 1 and Day 85) and 28 days after each vaccination (Day 29 and Day 113).</li>\n <li>\n Number of infants 9 months of age in Africa achieving a reference ELISA level equivalent to ≥1:1600** titre against S. sonnei LPS, before each vaccination (Day 1, Day 85, and Day 253) and 28 days after each vaccination (Day 29, Day 113, and Day 281).</li>\n </ul>\n <p>\n *This threshold (1:800, known as “Cohen’s Threshold”) has been previously reported to be potentially protective for Shigella [Cohen, 1988; Launay, 2017] and will be calibrated for the assay to be used in this study. The details of the equivalent threshold to be used will be reported in the Clinical Study Report (CSR).</p>\n <p>\n **This threshold (1:1600, double of “Cohen’s Threshold”) will be calibrated for the assay to be used in this study. The details of the equivalent threshold to be used will be reported in the CSR.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 222px;\">\n <ul>\n <li>\n To evaluate  seroresponse with the altSonflex1-2-3 vaccine after each vaccination in all participants in Africa (Stage 2).</li>\n </ul>\n </td>\n <td style=\"width: 438px;\">\n <ul>\n <li>\n Number of adults 18 to 50 years of age in Africa showing at least a 4-fold increase in anti-serotype specific Shigella LPS* serum IgG titres, as measured by reference ELISA, at 28 days after each vaccination (Day 29 and Day 113), compared to baseline (Day 1 and Day 85).</li>\n <li>\n Number of children 24 to 59 months of age showing at least a 4-fold increase in anti-serotype specific Shigella LPS* serum IgG titres, as measured by reference ELISA, at 28 days after each vaccination (Day 29 and Day 113), compared to baseline (Day 1 and Day 85).</li>\n <li>\n Number of infants 9 months of age showing at least a 4-fold increase in anti-serotype specific Shigella LPS* serum IgG titres, as measured by reference ELISA, at 28 days after each vaccination (Day 29, Day 113, and Day 281), compared to baseline (Day 1, Day 85, and Day 253).</li>\n </ul>\n <p>\n *S. sonnei, S. flexneri 1b, S. flexneri 2a, and S. flexneri 3a serotypes will be tested</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 222px;\">\n <ul>\n <li>\n To evaluate the immunogenicity of co-administered MR-VAC in infants 9 months of age in Africa (Stage 2), in the dose-finding cohort.</li>\n </ul>\n </td>\n <td style=\"width: 438px;\">\n <ul>\n <li>\n Anti-measles IgG concentrations, as measured by ELISA, in infants 9 months of age in Africa, in the dose-finding cohort, before the first MR-VAC (Day 1) and at 28 days after the second MR-VAC vaccination (Day 281).</li>\n <li>\n Anti-rubella IgG concentrations, as measured by ELISA, in infants 9 months of age in Africa, in the dose-finding cohort, before the first MR-VAC (Day 1) and at 28 days after the second MR-VAC vaccination (Day 281).</li>\n <li>\n Number of infants 9 months of age, in the dose-finding cohort, achieving anti-measles IgG concentrations of ≥150 mIU/mL* and ≥ 200 mIU/mL*, as measured by ELISA, at 28 days after the second MR-VAC vaccination (Day 281).</li>\n <li>\n Number of infants 9 months of age, in the dose-finding cohort, achieving anti-rubella IgG concentrations of ≥4 IU/mL* and ≥10 IU/mL*, as measured by ELISA, at 28 days after the second MR-VAC vaccination (Day 281).</li>\n </ul>\n <p>\n *This threshold is based on the vaccine correlate of protection and World Health Organization guidelines.</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width: 660px;\">\n <p align=\"center\">\n <strong>Tertiary</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 222px;\">\n <ul>\n <li>\n To evaluate the immune response induced by the Sonflex1-2-3 vaccine in 25% of infants 9 months of age in Africa (Stage 2), in the dose-finding cohort, using the serum bactericidal assay (SBA).</li>\n </ul>\n </td>\n <td style=\"width: 438px;\">\n <ul>\n <li>\n Anti-serotype specific* serum bactericidal antibody GMTs in 25% of infants 9 months of age in the dose-finding cohort, before each vaccination (Day 1, Day 85, and Day 253) and 28 days after each vaccination (Day 29, Day 113, and Day 281).</li>\n </ul>\n <p>\n *S. sonnei, S. flexneri 1b, S. flexneri 2a, and S. flexneri 3a serotypes will be tested.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 222px;\">\n <ul>\n <li>\n To further explore immune responses to the altSonflex1-2-3 vaccine in 25% of adults in Europe (Stage 1) and 25% of infants 9 months of age in Africa (Stage 2), in the dose finding</li>\n </ul>\n <p>\n cohort.</p>\n </td>\n <td style=\"width: 438px;\">\n <ul>\n <li>\n Antibody features (subclassing, affinity, avidity) and functional properties (induction of cellular phagocytosis and cellular cytotoxicity, natural killer [NK] cell activation, eosinophil and basophil degranulation, complement deposition, neutrophil activation/ phagocytosis, dendritic cell phagocytosis, mucin binding, glycosylation, and Fc receptor alteration), as measured by systems serology analysis</li>\n <li>\n Anti-serotype serum bactericidal antibody GMTs against a panel of vaccine heterologous Shigella serotypes, as measured by SBA</li>\n <li>\n Anti-serotype serum bactericidal antibody GMTs against a panel of vaccine homologous and heterologous Shigella serotypes, as measured by opsonophagocytosis assay</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • trial_administration_humans1
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n The Kericho CRC, established in 1998, is located 260 km Northwest of Nairobi in Kericho town on the grounds of the Ministry of Health, Kericho County Referral Hospital. USAMRD-K has been in Kenya for 47 years and has partnered with KEMRI since 1980. KEMRI is a Government of Kenya para-state corporation responsible for health research. The CRC has three integrated main components: HIV care, HIV vaccine and microbiology research. Since 2003, the CRC has been conducting diverse studies including randomized, double-blind, placebo controlled and IND/FDA-regulated studies.</p>\n<p>\n The site has a long-standing experience in conducting more than 52 studies including clinical trials, ranging from therapeutics, vaccines (HIV, Polio, Ebola) to cohort studies. The clinical trials range from phase I to IV with age ranges from birth to the elderly, some of which are randomized double-blind, placebo controlled and IND/FDA-regulated. The site has conducted 3 Phase I HIV vaccine trials, 1 Phase I Ebola vaccine trial and 1 Phase III Polio vaccine trial. Kericho CRC has a total of 152 staff members with the necessary professional background and experience to support the clinical trial implementation. The staff consists of 6 doctors (1 obstetrician/gynecologist, 2 infectious disease doctors, 1 public health physician, 1 consultant pediatrician, and 1 medical officer), 15 clinical officers, 2 pharmacists, 1 pharmaceutical technologist, and 14 nurses.</p>\n<p>\n The Kericho CRC is equipped with two emergency rooms (one per floor) to provide immediate emergency care in the event of emergencies during vaccinations such as anaphylaxis, cytokine release syndrome, convulsions, hypotension, and resuscitation equipment are in place for immediate intervention on site. Additionally, the Kericho site has a standby, fully equipped ambulance for evacuation of participants for more specialized care when necessary. The Kericho County Referral Hospital, on whose compound the CRC sits in, has an Intensive Care Unit (ICU) which will be utilized should need arise. The site has 5 full time doctors that will participate in study implementation and participants’ care, one of whom is a Critical Care Pediatrician, and will be available to oversee participants during vaccinations. The study staff (clinicians/nurses) are trained on handling emergencies.</p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n higellosis remains a major public health problem around the world; it is one of the leading causes of diarrheal disease in low- and middle-income countries (LMIC), particularly in young children. The Global Burden of Disease study (IHME) estimated that in 2017 Shigella caused approximately 238,000 deaths globally and, with 15.2%, it ranked second with regard to pathogen contributions in global diarrheal deaths. In infants, in LMIC, particularly where healthcare resources are limited, shigellosis can often lead to death.  There is presently no widely available vaccine against Shigella. Treatment for shigellosis is mainly supportive to keep patients stable and restore lost electrolytes due to diarrhea. If available, specific antibiotics are sometimes used for severe cases of shigellosis.</p>\n<p>\n Current drugs are under threat from the increasing rates of antibiotic resistance in Shigella serotypes around the world. Prevention of diarrheal diseases caused by Shigella, with the introduction of an efficacious vaccine is important.</p>\n
      • other_details_regulatory_notapproved<p>\n Scientific Ethics Review Unit KEMRI</p>\n<p>\n <span style=\"color: rgb(77, 81, 86); font-family: arial, sans-serif; font-size: 14px;\">P.O. Box 54840 00200 </span></p>\n<p>\n <span style=\"color: rgb(77, 81, 86); font-family: arial, sans-serif; font-size: 14px;\">Off Raila Odinga Way.</span></p>\n<p>\n <span style=\"color: rgb(77, 81, 86); font-family: arial, sans-serif; font-size: 14px;\">Nairobi, Kenya. </span></p>\n<p>\n <span style=\"color: rgb(77, 81, 86); font-family: arial, sans-serif; font-size: 14px;\">Tel: +254 722205901</span></p>\n<p>\n  </p>\n<p>\n <font color=\"#4d5156\" face=\"arial, sans-serif\"><span style=\"font-size: 14px;\">Application submitted 04 May 2022.</span></font></p>\n
      • other_details_regulatory_approved<p>\n None</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration5 years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatoraltSonflex Placebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI WRP CRC KERICHO
      • single_site_physical_addressoff Hospital Road
      • single_site_contact_personDr Deborah Langat
      • single_site_telephone+254 714059596
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states3
      • number_of_sites
      • multi_country_listEurope, USA, Africa
      • data_monitoring_committeeYes
      • total_enrolment_per_sitenone
      • total_participants_worldwide1000
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentNo
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Fredrick Sawe
      • investigator1_middle_name
      • investigator1_family_nameSawe
      • investigator1_qualificationMedical Doctor
      • investigator1_professional_address1357, Kericho
      • investigator1_telephone+254 703 247 902
      • investigator1_emailFredrick.sawe@usamru-k.org
      • organisations_transferred_No
      • number_participants448
      • notification
      • approval_date23-11-2022
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted25-08-2022
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-03 15:51:39
      • created2022-05-16 08:44:16
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id822
        • application_id1145
        • given_nameDeborah Chepngeno Langat
        • middle_name
        • family_nameLangat
        • qualificationMedical Doctor
        • professional_address1357, Kericho
        • telephone254 714059596
        • emailDeborah.langat@usamru-k.org
        • created2022-05-16 10:40:17
        • modified2022-08-25 12:54:26
    • SiteDetail(array)
      • 0(array)
        • id1278
        • application_id1145
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2022-05-16 10:40:17
        • modified2022-08-25 12:54:26
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id592
        • application_id1145
        • sponsorGlaxoSmithKline Biologicals SA (GSK).
        • sponsor_typeIndustry
        • contact_person
        • addressRue de l\'Institut 89 Rixensart, 1330 Belgium
        • telephone_number32-2-656-81-11
        • fax_number
        • cell_number32-2-656-81-11
        • email_addresspietro.x.ferruzzi@gsk.com
        • created2022-05-16 10:40:17
        • modified2022-08-25 12:54:26
  • 1(array)
    • Application(array)
      • id240
      • user_id613
      • trial_status_id5
      • abstract_of_study<div>\n <p style=\"margin-left:.25in;\">\n Acquired immunodeficiency syndrome-related Kaposi’s sarcoma (AIDS-KS) occurs in persons who are coinfected with human immunodeficiency virus type 1(HIV-1) and kaposi’s sarcoma-associated herpes virus (KSHV).  Although the availability of potent antiretroviral therapy (ART) has coincided with a substantial decrease in AIDS-KS incidence in the developed world, AIDS-KS remains a significant cause of morbidity and mortality in HIV-1 infected persons in areas of the world where access to ART and chemotherapy is limited.  Because AIDS-KS is a malignancy that results from HIV-1-related immunosuppression, optimal management of this disease may require immune reconstitution by treatment of HIV-1 infection with ART and treatment of KS disease.  KS disease stage is an important factor associated with prognosis of AIDS-KS.  Stage T0 disease is associated with better clinical outcome compared to stage T1 disease.  Advanced -KS is usually treated with combined ART and chemotherapy, but limited AIDS-KS often responds to ART alone. Current Kenya ministry of Health guidelines recommends use of highly active antiretroviral therapy (HAART) in the management of limited stage KS and use of chemotherapy for the treatment of advanced KS. The primary objective of the study is to compare in participants with limited stage KS, the week 48 KS tumor outcomes of low dose concurrent administration of oral etoposide with ART to ART alone or ART with delated etoposide with outcome at week 48 compared to entry categorized into; treatment failure where KS progresses despite treatment, Stable disease where there is no KS progression or response to therapy or response where there is response of KS to treatment. This is A phase III, open-label, prospective, randomized study stratified by CD4+ lymphocyte cell count and antiretroviral therapy (ART) history. The participants (male and female) must be 18 years and above with documented HIV-1 infection and must have a biopsy diagnostic of KS. They must not have used radiation and chemotherapy treatment for KS and, are currently not receiving ARTor are pregnant.  At study entry participants will be randomized 1:1 to either arm 1A (Efavirenz/emtricitabine/tenofovir) or arm 1B where they will receive (EFV/FTC/TDF) and ET.  Those on etoposide will receive an initial single dose of 50mg/day taken from day 1-7 of each 2-week cycle. For participants without partial response or complete response after two cycles of therapy with no toxicity of more than G2 the dose of etoposide will be escalated to 100mg/day orally, days 1-7, every 2 weeks.  ET may be administerd up to a maximum of eight cycles. Participants in arm 1A who experience KS progression will enter step 2 and receive oral etoposide. The Kericho site will recruit 40-60 participants. Recruitment will primarily be done through Kericho District Hospital HIV clinic. The site accrual will be approximately 4 participants per month; hence estimated duration of accrual of 10-15months.  Participants who will receive HAART only, will be followed up for 96 weeks while those who will receive  oral etoposide with HAART will be followed up for 240 weeks.  If the immediate use low dose etoposide given together with HAART shows better KS tumor outcome; this may lead to a decrease in the morbidity/mortality among patients infected with HIV-1andKaposissarcoma.</p>\n</div>\n<p>\n  </p>\n
      • study_title<p align=\"center\">\n A Randomized Evaluation of Antiretroviral Therapy Alone or with Delayed Chemotherapy versus Antiretroviral Therapy with Immediate Adjunctive Chemotherapy for Treatment of Limited Stage AIDS-KS in Resource-Limited Settings (REACT-KS)</p>\n
      • laymans_summary<p>\n Kaposi’s sarcoma is the most common cancer seen in HIV-infected patients. Limited stage Kaposi’s sarcoma means the Kaposi’s sarcoma is not very advanced. AIDS-related Kaposi’s sarcoma (AIDS-KS) occurs in persons with HIV infection, who are also infected with the Kaposi’s sarcoma herpes virus (KSHV). Several chemotherapy (anti-cancer) drugs work well in treating Kaposi’s sarcoma; but there is no treatment that cures KSHV infection.  One chemotherapy drug called etoposide has caused Kaposi sarcoma tumors to get smaller in some people.  Antiretroviral therapy (anti-HIV drugs or ART) is a group of medicines taken together to treat HIV infection.  These medicines help to stop replication of HIV in the body.  When this happens, the immune system, which fights infection and some cancers like Kaposi’s sarcoma, improves.  For some people, limited stage Kaposi’s sarcoma often improves or stays the same when they take ART. However, in some people Kaposi’s sarcoma gets worse when taking ART. These people may need chemotherapy at a later date</p>\n<p>\n Taking ART has been shown to be helpful in treating KS as well as HIV infection. Taking additional anti-cancer medications may be beneficial as well. This study is being done to find out if taking ART with etoposide is better than taking ART alone or ART with delayed etoposide to treat limited stage KS. The study will also try to better understand KSHV, and to see what kind of side effects are caused by ART and etoposide, and how safe ART and etoposide are</p>\n<p>\n Each participant will be assigned (by chance) to one of two treatment groups; ART alone or ARTcombined with an anti-cancer drug called Etoposide. There will be a total of 468 participants in the study, 234 in each treatment group. The Kericho site will recruit 40-60 participants, both male and female of 18 years and above with documented HIV-1 infection and must have a biopsy diagnostic of Kaposi’s sarcoma.</p>\n
      • short_titleRandomized Comparison of ART Alone versus ART with Immediate Chemotherapy
      • protocol_noECCT/11/09/01
      • version_no1.4
      • date_of_protocol11-11-2011
      • study_drugOral Etoposide.
      • disease_conditionKaposi\'s Sarcoma
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameEtoposide
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameART alone
      • comparator_registeredyes
      • comparator_countriesKenya
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressekavai@wrp-kch.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantEverlyne K Amunavi- Study Co ordinator. KEMRI/WRP Kericho Box 1357 Kericho.
      • declaration_date104-12-2013
      • declaration_principal_investigatorDr. Fredrick Kirui-PI KEMRI/WRP Kericho Box 1357 Kericho.
      • declaration_date204-12-2013
      • placebo_presentNo
      • study_objectives<h1>\n Primary Objective</h1>\n<p style=\"margin-left:.5in;\">\n 1. To compare, in participants with limited stage Kaposi’s sarcoma (KS), the week 48 KS tumor outcomes of low-dose concurrent administration of oral ET with ART to ART alone or ART with delayed ET with outcome at week 48 compared to entry categorized into one of three categories:</p>\n<p style=\"margin-left:1.0in;\">\n E1 (Failure) = KS progression at week 48 compared to study entry, initiation of a new KS treatment (chemotherapy agent other than ET or other treatment triggered by worsening KS) by week 48, or lost to follow-up at  week 48 (including death and lost to follow-up by week 48 and missed visit at week 48);</p>\n<p style=\"margin-left:1.0in;\">\n E2 (Stable) = Without KS progression nor KS partial response (PR), nor complete response (CR) at week 48 compared to study entry, and without initiation of a new KS treatment (chemotherapy agent other than ET or other treatment triggered by worsening KS) by week 48,</p>\n<p style=\"margin-left:1.0in;\">\n E3 (Response) = With KS partial response (PR) or complete response (CR) at week 48 compared to study entry and without initiation of a new KS treatment (chemotherapy agent other than ET or radiation therapy triggered by worsening KS) by week 48.</p>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<h1>\n Secondary Objectives</h1>\n<p style=\"margin-left:1.0in;\">\n 1    To evaluate the effects of randomized study treatment on the rate of KS clinical response. This will include comparison of the time to initial KS progression and suspected KS IRIS (KS-associated immune reconstitution inflammatory syndrome), time to initial KS response (PR and CR combined and separately), and KS progression and response (compared to study entry) rates at weeks 48 and 96.</p>\n<p style=\"margin-left:1.0in;\">\n 2      To evaluate the safety and tolerability of randomized study treatment.  This will include comparison of adverse events, dose-limiting toxicities, and treatment/dose changes related to management of toxicities.</p>\n<p style=\"margin-left:1.0in;\">\n 3      To investigate the effects of randomized study treatment on quality of life.</p>\n<p style=\"margin-left:1.0in;\">\n 4      To compare the effects of randomized study treatment on plasma HIV-1 RNA levels and peripheral blood CD4+ T-cell counts including both magnitudes and rates of change.</p>\n<p style=\"margin-left:1.0in;\">\n 5      To evaluate the effects of concomitant ET on adherence to ART.</p>\n<p style=\"margin-left:1.0in;\">\n 6      To investigate the response to delayed ET after KS progression on ART alone.</p>\n<p style=\"margin-left:1.0in;\">\n 7      To determine baseline KS-associated herpesvirus (KSHV) viral load in plasma and peripheral blood mononuclear cells (PBMCs), compare the effects of randomized study treatment on KSHV viral load changes, and evaluate the relationship of KSHV viral load changes to KS clinical response.</p>\n<p style=\"margin-left:1.0in;\">\n 8      To evaluate the relationship between response of KS to randomized treatment, development of KS-IRIS, and the following markers:</p>\n<p style=\"margin-left:1.0in;\">\n 8.1 Baseline immunohistochemical markers of viral and cellular gene expression in KS tumors</p>\n<p style=\"margin-left:1.0in;\">\n 8.2 RNA levels for genes in tumor biopsies at baseline and during therapy</p>\n<p style=\"margin-left:1.0in;\">\n 8.3 Cellular and humoral markers of immune function and immune activation.</p>\n<p style=\"margin-left:1.0in;\">\n 9      To investigate the relationship between plasma, and PBMC KSHV viral load.</p>\n<p style=\"margin-left:1.0in;\">\n 10   To encourage donation of excess biopsy materials to the AIDS and Cancer Specimen Resource (ACSR).</p>\n<p style=\"margin-left:1.0in;\">\n 11   To assess the risk of secondary leukemia and myelodysplasia after etoposide use.</p>\n<p style=\"margin-left:1.0in;\">\n 12   To compare the effects of randomized treatment on serum levels of inflammatory cytokines and/or molecules associated with angiogenesis.</p>\n<p>\n                   13   To determine whether serum levels of cytokines and angiogenesis-associated molecules are associated with clinical response, immunological response (assessed by measuring CD4 T cell numbers), virological responses (assessed by measurement of HIV-1 and KSHV viral load), and the development of IRIS</p>\n<p style=\"margin-left:1.0in;\">\n 14   To determine anti-KSHV specific T cell immune response in patients with AIDS-related KS before and after ART.</p>\n<p style=\"margin-left:1.0in;\">\n 15   To follow the trajectory of the anti-KSHV T cell response at various time points   after ART is started.</p>\n<p style=\"margin-left:1.0in;\">\n 16   To correlate changes in the anti-KSHV T cell response with both HIV and KSHV viremia at specific time points.</p>\n<p style=\"margin-left:1.0in;\">\n 17   To correlate the magnitude of the anti-KSHV T cell immune response with clinical outcome.</p>\n<p style=\"margin-left:.5in;\">\n               18 To explore changes in regulatory T cell frequency in patients developing KS-IRIS.</p>\n<p>\n                             19 To evaluate CD8+ T cell exhaustion before and after ART treatment and during the development of KS-IRIS.</p>\n<p>\n                             20 To determine the effects of randomized treatment on KS as a function of patterns of viral gene expression</p>\n<p>\n                             21 To determine the effect of the treatment on KSHV viral gene expression in tumors we will be utilizing a RT-QPCR (Quantitive polymerase                                             chain reaction) for KSHV</p>\n
      • principal_inclusion_criteria<ul style=\"list-style-type:circle;\">\n <li>\n HIV-1 infection, documentation; for the Kericho site, HIV-1 infection will be confirmed based upon 2 consecutive Elisa (Genetic systems biorad) and a Western Blot (Genetics systems biorad).</li>\n <li>\n Biopsy diagnostic of KS at any time prior to study entry.</li>\n <li>\n Current limited stage KS using the ACTG criteria [1].</li>\n</ul>\n<p style=\"margin-left:1.0in;\">\n Note: Limited stage KS is defined as stage T0 and some presentations of stage T1 KS. Stage T0 KS: Confined to skin and/or lymph nodes and/or minimal oral disease. Minimal oral disease is defined as non-nodular KS confined to the palate.</p>\n<p style=\"margin-left:1.0in;\">\n The following presentations of stage T1 KS are also eligible at the discretion of the site investigator:</p>\n<ul>\n <li>\n Tumor-associated edema limited to the area(s) of KS without significant functional impairment.</li>\n <li>\n Oral KS that consists of flat (non-nodular and non-ulcerating) lesions confined to the soft palate, hard palate, gums, and buccal mucosa.</li>\n <li>\n Asymptomatic gastrointestinal KS (i.e., no unexplained abdominal pain or gastrointestinal bleeding).</li>\n</ul>\n<p>\n � � � � � � � � � � � �</p>\n<ul style=\"list-style-type:circle;\">\n <li>\n A minimum of 5 cutaneous marker lesions</li>\n</ul>\n<p>\n �</p>\n<ul style=\"list-style-type:circle;\">\n <li>\n The following laboratory values obtained at the KEMRI/WRP laboratory within 14 days prior to study entry:</li>\n</ul>\n<ul>\n <li>\n Absolute neutrophil count (ANC) ³ 1,000 cells/mm³.</li>\n <li>\n Hemoglobin ³ 9.0 g/dL.</li>\n <li>\n Platelet count ³ 100,000/mm³.</li>\n <li>\n Calculated creatinine clearance of ≥ 60 mL/min using the Cockroft-Gault formula</li>\n <li>\n AST (SGOT), ALT (SGPT), and alkaline phosphatase < 5 ´ ULN.</li>\n <li>\n Total bilirubin of <u><</u> 1.5 X ULN.</li>\n</ul>\n<p>\n �</p>\n<ul style=\"list-style-type:circle;\">\n <li>\n Female participants of reproductive potential must have a negative serum or urine pregnancy test performed within 1 day � prior to study entry.</li>\n</ul>\n<p style=\"margin-left:1.0in;\">\n “Female participants of reproductive potential” is defined as women who have reached menarche or who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months) or have not undergone surgical sterilization (e.g., hysterectomy, or bilateral oophorectomy, salpingectomy, or tubal ligation).�</p>\n<ul style=\"list-style-type:circle;\">\n <li>\n All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).</li>\n</ul>\n<p style=\"margin-left:61.5pt;\">\n If participating in sexual activity that could lead to pregnancy, study participants must agree to use two reliable forms of contraceptives simultaneously while receiving protocol-specified medications and for 6 weeks after stopping the medications</p>\n<p style=\"margin-left:70.9pt;\">\n Study participants who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy and/or bilateral oophorectomy or men who have documented azoospermia) are eligible without the use of contraceptives. Acceptable documentation of sterilization and menopause is specified on the A5264 PSWP</p>\n<ul style=\"list-style-type:circle;\">\n <li>\n Ability to swallow oral medications.</li>\n</ul>\n
      • principal_exclusion_criteria<ul style=\"list-style-type:circle;\">\n <li>\n Any manifestation of KS which, in the opinion of the site investigator, requires immediate chemotherapy.</li>\n</ul>\n<p style=\"margin-left:1.0in;\">\n NOTE: A chest x-ray must be performed within 30 days prior to study entry to evaluate for presence of pulmonary KS, which would indicate T1 disease and generally require chemotherapy.</p>\n<ul style=\"list-style-type:circle;\">\n <li>\n Receipt of ART within 6 months prior to study entry.</li>\n</ul>\n<p style=\"margin-left:57.0pt;\">\n �</p>\n<ul style=\"list-style-type:circle;\">\n <li>\n Biopsy proven KS during previous ART.</li>\n</ul>\n<p>\n �</p>\n<ul style=\"list-style-type:circle;\">\n <li>\n Breastfeeding.</li>\n</ul>\n<p>\n �</p>\n<ul style=\"list-style-type:circle;\">\n <li>\n Allergy/sensitivity to any study drug or its formulations.</li>\n</ul>\n<p>\n �</p>\n<ul style=\"list-style-type:circle;\">\n <li>\n Any prior systemic anti-neoplastic treatment for KS (including chemotherapy, biological therapy, immunotherapy or� � investigational therapy).</li>\n</ul>\n<p>\n �</p>\n<ul style=\"list-style-type:circle;\">\n <li>\n Any prior local treatment of cutaneous marker lesions unless there was evidence of a clear-cut progression of the lesion.</li>\n</ul>\n<p>\n �</p>\n<ul style=\"list-style-type:circle;\">\n <li>\n Receipt of any investigational therapy within 30 days prior to study entry.</li>\n</ul>\n
      • primary_end_points<p style=\"margin-left:1.0in;\">\n A composite endpoint incorporating KS tumor response, KS progression, loss to follow-up, and initiation of new chemotherapy agent other than ET, as an ordinal, categorical outcome.</p>\n<p>\n <br />\n �</p>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n See the Site specific adendum section 10 on Study site description</p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n KEMRI ERC and WRAIR</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration2-5 years.
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorART alone.
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI/Walter Reed Project
      • single_site_physical_addressClinical Research Centre,Off Hospital Road, Kericho.
      • single_site_contact_personDeborah Langat
      • single_site_telephone+254 52 20 36100
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states6
      • number_of_sites
      • multi_country_listKenya, Uganda, Malawi, Zimbabwe, Brazil, South Africa,
      • data_monitoring_committeeYes
      • total_enrolment_per_siteN/A
      • total_participants_worldwide468
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameEverlyne
      • investigator1_middle_name
      • investigator1_family_nameKavai
      • investigator1_qualificationBSc Nursing
      • investigator1_professional_addressKEMRI Walter Reed Project, Kericho Hospital Road, P.O Box 1357-20200
      • investigator1_telephoneN/A
      • investigator1_emailEverlyne.amunai@usamru-k.org
      • organisations_transferred_Yes
      • number_participants40-60
      • notification<p>\n NO</p>\n
      • approval_date19-08-2011
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted18-05-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"1053\">\n <tbody>\n <tr>\n <td style=\"width:702px;height:18px;\">\n <p>\n <strong>A. Study Status at Close-out:</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:85px;\">\n <p>\n [X] Study was completed</p>\n <p>\n [] Study was started but closed prior to completion</p>\n <p>\n [] Study was not started</p>\n <p>\n [] Study is being transferred to another institution</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:24px;\">\n <p>\n <strong>B. Provide a summary of research objectives:</strong></p>\n <p>\n <strong><em>Primary Objective</em></strong></p>\n <ol>\n <li>\n To compare, in participants with limited stage Kaposi’s sarcoma (KS), the week 48 KS tumor outcomes of low-dose concurrent administration of oral ET with ART to ART alone or ART with delayed ET with outcome at week 48 compared to entry categorized into one of three categories:</li>\n </ol>\n <p>\n  </p>\n <p>\n E1 (Failure) = KS progression at week 48 compared to study entry, initiation of a new KS treatment (chemotherapy agent other than ET or other treatment triggered by worsening KS) by week 48, or lost to follow-up at week 48 (including death and lost to follow-up by week 48 and missed visit at week 48);</p>\n <p>\n  </p>\n <p>\n E2 (Stable) = Without KS progression nor KS partial response (PR), nor complete response (CR) at week 48 compared to study entry, and without initiation of a new KS treatment (chemotherapy agent other than ET or other treatment triggered by worsening KS) by week 48,</p>\n <p>\n  </p>\n <p>\n E3 (Response) = With KS partial response (PR) or complete response (CR) at week 48 compared to study entry and without initiation of a new KS treatment (chemotherapy agent other than ET or radiation therapy triggered by worsening KS) by week 48.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:499px;\">\n <p>\n <strong><em>Secondary Objectives</em></strong></p>\n <ol>\n <li>\n To evaluate the effects of randomized study treatment on the rate of KS clinical response. This will include comparison of the time to initial KS progression and suspected KS IRIS (KS-associated immune reconstitution inflammatory syndrome), time to initial KS response (PR and CR combined and separately), and KS progression and response (compared to study entry) rates at weeks 48 and 96.</li>\n <li>\n To evaluate the safety and tolerability of randomized study treatment.  This will include comparison of adverse events, dose-limiting toxicities, and treatment/dose changes related to management of toxicities.</li>\n <li>\n To investigate the effects of randomized study treatment on quality of life.</li>\n <li>\n To compare the effects of randomized study treatment on plasma HIV-1 RNA levels and peripheral blood CD4+ T-cell counts including both magnitudes and rates of change.</li>\n <li>\n To evaluate the effects of concomitant ET on adherence to ART.</li>\n <li>\n To investigate the response to delayed ET after KS progression on ART alone.</li>\n <li>\n To determine baseline KS-associated herpesvirus (KSHV) viral load in plasma and peripheral blood mononuclear cells (PBMCs), compare the effects of randomized study treatment on KSHV viral load changes, and evaluate the relationship of KSHV viral load changes to KS clinical response.</li>\n <li>\n To evaluate the relationship between response of KS to randomized treatment, development of KS-IRIS, and the following markers:\n <ol style=\"list-style-type:lower-alpha;\">\n <li>\n Baseline immunohistochemical markers of viral and cellular gene expression in KS tumors</li>\n <li>\n RNA levels for genes in tumor biopsies at baseline and during therapy</li>\n <li>\n Cellular and humoral markers of immune function and immune activation.          </li>\n </ol>\n </li>\n <li>\n To investigate the relationship between plasma, and PBMC KSHV viral load.</li>\n <li>\n To encourage donation of excess biopsy materials to the AIDS and Cancer Specimen Resource (ACSR).</li>\n <li>\n To assess the risk of secondary leukemia and myelodysplasia after etoposide use.</li>\n <li>\n To compare the effects of randomized treatment on serum levels of inflammatory cytokines and/or molecules associated with angiogenesis.</li>\n <li>\n To determine whether serum levels of cytokines and angiogenesis-associated molecules are associated with clinical response, immunological response (assessed by measuring CD4 T cell numbers), virological responses (assessed by measurement of HIV-1 and KSHV viral load), and the development of IRIS</li>\n <li>\n To determine anti-KSHV specific T cell immune response in patients with AIDS-related KS before and after ART.</li>\n <li>\n To follow the trajectory of the anti-KSHV T cell response at various time points   after ART is started.</li>\n <li>\n To correlate changes in the anti-KSHV T cell response with both HIV and KSHV viremia at specific time points.</li>\n <li>\n To correlate the magnitude of the anti-KSHV T cell immune response with clinical outcome.</li>\n <li>\n To explore changes in regulatory T cell frequency in patients developing KS-IRIS.</li>\n <li>\n To evaluate CD8+ T cell exhaustion before and after ART treatment and during the development of KS-IRIS.</li>\n <li>\n To determine the effects of randomized treatment on KS as a function of patterns of viral gene expression.</li>\n <li>\n To determine the effect of the treatment on KSHV viral gene expression in tumors we will be utilizing a RT-QPCR (Quantitive polymerase chain reaction) for KSHV.</li>\n </ol>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:46px;\">\n <p>\n <strong>C. Summary of Study Results: </strong>Please summarize the results of this research project, even if only for the study cohort enrolled locally.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:35px;\">\n <p>\n  </p>\n <p>\n In Kericho, recruitment of potential study participants started on 01 Mar 2012 and the site screened 12 participants and enrolled 11 participants (6 males and 5 females). One participant was screened out because he was ineligible with advanced stage Kaposis sarcoma. Of the 11 participants enrolled, 2 died, 1 withdrew from the study due to family social issues, and 8 have completed study visit. Up to 60 study participants were approved for enrollment at the KEMRI/WRP Kericho site, Kenya. A total of 192 participants were enrolled in all the international sites out of target 468 participants. This is because the study was closed to accrual on 18 March 2016 after DSMB recommended that the study be closed for futility, this was submitted to SERU. The last study visit for all international sites was on 29 Nov 2018 and the study is now closed to follow up.</p>\n <p>\n  </p>\n <p>\n <strong>Methods.</strong> Chemotherapy-naive, HIV type 1–infected adults with mild-to-moderate KS initiating ART in Africa and South America were randomized to ART (tenofovir/emtricitabine/efavirenz) alone (chemotherapy “as-needed” arm) vs ART plus up to 8 cycles of oral ET (immediate arm). Participants with KS progression on ART alone received ET as part of the as-needed strategy. Primary outcome was ordinal as follows: failure, stable, and response at 48 weeks. Secondary outcomes included time to initial KS progression, KS-associated immune reconstitution inflammatory syndrome (KS-IRIS), and KS response.</p>\n <p>\n <strong>Results.</strong> Of 190 randomized participants (as-needed = 94, immediate = 96), the majority were men (71%) and African (93%). Failure (53.8% vs 56.6%), stable (16.3% vs 10.8%), and response (30% vs 32.5%) did not differ between arms (as-needed vs immediate) among those with week 48 data potential (N = 163, P = .91). Time to KS progression (P = .021), KS-IRIS (P = .003), and KS response (P = .003) favored the immediate arm. Twenty-five participants died (13%). Mortality, adverse events, CD4+ T-cell changes, and HIV RNA suppression were similar at 48 weeks.</p>\n <p>\n <strong>Conclusions.</strong> Among HIV-infected adults with mild-to-moderate KS, immediate ET provided early, nondurable clinical benefits. By 48 weeks, no clinical benefit was observed compared to use of ET as needed. Mortality was high and tumor response was low.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:41px;\">\n <p>\n <strong>D. List Outputs arising from study e.g. Manuscripts, Thesis, Research Reports, Technical Briefs, Policy Briefs, Abstracts, Patents, Book Chapter etc. (attach copies of the outputs(s). </strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:339px;\">\n <ul style=\"list-style-type:circle;\">\n <li>\n Manuscripts\n <ul>\n <li>\n Published in 2018 - As-Needed Vs Immediate Etoposide Chemotherapy in Combination with Antiretroviral Therapy for Mild to-Moderate AIDS-Associated Kaposi Sarcoma in Resource-Limited Settings: A5264/AMC-067 Randomized Clinical Trial. </li>\n <li>\n Published in 2019 - Interim monitoring in a treatment strategy trial with a composite primary endpoint</li>\n <li>\n Published in 2020 - Early Progression and Immune Reconstitution Inflammatory Syndrome During Treatment of Mild-To-Moderate Kaposi Sarcoma in Sub-Saharan Africa and South America: Incidence, Long-Term Outcomes, and Effects of Early Chemotherapy.</li>\n </ul>\n </li>\n <li>\n Abstracts\n <ul>\n <li>\n Immediate vs. delayed oral etoposide (ET) among HIV-infected individuals with limited-stage KS initiating ART: A5264/AMC-067 study – Presented at IAS Conference on HIV Science (IAS 2017)</li>\n <li>\n As-Needed versus Immediate Etoposide Chemotherapy in Combination with Antiretroviral Therapy for Mild or Moderate AIDS-associated Kaposi Sarcoma in Resource-Limited Settings: A5264/AMC-067 – Presented at International Conference on Malignancies in HIV/AIDS (ICMH) in 2017 (ICMH 2017).</li>\n <li>\n Predictors of KS-IRIS in mild/moderate AIDS-KS during ART in low-resource settings – presented at 2018 Annual Conference on Retroviruses and Opportunistic Infections (CROI 18).</li>\n </ul>\n </li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:14px;\">\n <ol style=\"list-style-type:upper-alpha;\">\n <li value=\"5\">\n <strong>Confirm destruction of each study participant’s identifiers and provide an assurance/evidence that the destruction has occurred (send copies of the blacked-out books). </strong></li>\n </ol>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:31px;\">\n <p>\n Study documents have been transferred to a safe, secured, long-term archive room that is only accessible to regulatory personnel. All other research staff do not have access to this archive room. Access to study documents is controlled and restricted and the site is responsible for ensuring that any access is accurately recorded and any documents accessed/removed and returned are recorded. Destruction approval will be obtained from the sponsor and the IRBs will be notified when this is done.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;\">\n <p>\n <strong>F. Detail the plan for future use of data from the study (if applicable) </strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:33px;\">\n <ul style=\"list-style-type:circle;\">\n <li>\n There are currently no plans for future analysis of individual participant data by study site personnel. Analysis of aggregated data and publication for secondary objectives will continue.</li>\n <li>\n Any plans for future (non-aggregated) analyses will be reviewed and approved by KEMRI SERU prior to the work being completed.</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;\">\n <p>\n <strong>G. Confirm destruction of surplus investigational agents and provide an assurance/evidence that the destruction has occurred (if applicable) </strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:25px;\">\n <table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:646px;height:18px;\">\n <p>\n Find attached A5264 Study Product Recovery Report.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:646px;height:4px;\">\n <p>\n  </p>\n </td>\n </tr>\n </tbody>\n </table>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;\">\n <p>\n <strong>H. Detail the plan for the destruction, storage, or future use of biological specimens obtained as part of this study (include number of samples being destroyed or stored) </strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:42px;\">\n <p style=\"margin-left:.25pt;\">\n All work for this study is complete and the samples that were not for safety testing were all shipped out with the approval of KEMRI ERC for analysis. Future use of individually coded data will have to be approved by the IRB. Participants were informed through the informed consent forms that they signed, that the stored samples may be shipped out of the country and used for future ACTG -approved HIV related research, which will help understand Kaposis Sarcoma/HIV better. The participants were also made aware that any use of the samples and stored data whether locally or out of the country will have to be approved by Kenya Medical Research Institute Ethical Review Committee.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;\">\n <p>\n <strong>I. Were the study results communicated to the local community? If yes provide details where and when- if not kindly explain why not.</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:27px;\">\n <p>\n The study results have been communicated to the local community through continuous medical education and meeting with the community Advisory Board as well as meetings organized in the community.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;\">\n <p>\n <strong>J. Is there a policy implication or best practice that should be forwarded to the MOH or any relevant authority?  </strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:47px;\">\n <p>\n Yes, from the Publication:</p>\n <ul style=\"list-style-type:circle;\">\n <li>\n The findings highlight the need for continued research into interventions capable of improving the suboptimal outcomes of individuals with mild-to-moderate KS. Until such interventions are found, clinicians in resource-limited settings should recognize the lack of evidence supporting immediate adjunctive treatments for mild-to-moderate KS beyond ART alone.</li>\n <li>\n Decisions about whether to initiate chemotherapy together with ART for AIDS-KS must consider both the potential benefits and the added toxicities of chemotherapy plus ART over ART alone. World Health Organization guidelines recommend immediate ART initiation in combination with systemic chemotherapy for persons with severe or symptomatic KS. Initiating chemotherapy and ART together effectively decreased early KS-PD, including KS-IRIS provides additional support for these recommendations.</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • implication_results<p>\n Yes, from the Publication:</p>\n<p>\n Ø  The findings highlight the need for continued research into interventions capable of improving the suboptimal outcomes of individuals with mild-to-moderate KS. Until such interventions are found, clinicians in resource-limited settings should recognize the lack of evidence supporting immediate adjunctive treatments for mild-to-moderate KS beyond ART alone.</p>\n<p>\n Decisions about whether to initiate chemotherapy together with ART for AIDS-KS must consider both the potential benefits and the added toxicities of chemotherapy plus ART over ART alone. World Health Organization guidelines recommend immediate ART initiation in combination with systemic chemotherapy for persons with severe or symptomatic KS. Initiating chemotherapy and ART together effectively decreased early KS-PD, including KS-IRIS provides additional support for these recommendations. </p>\n
      • quantity_importedFind attached product accountability documents
      • quantity_dispensedFind attached product accountability documents
      • quantity_destroyedFind attached product accountability documents
      • quantity_exportedFind attached product accountability documents
      • balance_site0
      • final_date0000-00-00
      • modified2023-04-25 12:45:25
      • created2013-12-03 11:29:37
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id173
        • application_id240
        • given_nameDeborah
        • middle_nameC.
        • family_nameLangat
        • qualificationMBChB, MSc
        • professional_addressKenya Medical Research Institute/ Walter Reed Project,P.o box 1357, Hospital Road, Kericho,Kenya,20200,
        • telephone052 20 36100
        • emailDeborah.langat@usamru-k.org
        • created2013-12-03 11:41:07
        • modified2020-05-18 15:38:24
    • SiteDetail(array)
      • 0(array)
        • id217
        • application_id240
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2013-12-03 11:41:07
        • modified2020-05-18 15:38:24
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id139
        • application_id240
        • sponsorNational Institute of Allergy and infectious diseases, National Cancer Intitute and National Institute of Dental Craniofacial Research.
        • sponsor_typeResearch Institution
        • contact_person
        • addressHIV Research Branch TRP, DAIDS, NIAID, NIH 6700B Rockledge Drive Bethesda, MD 20892
        • telephone_number+1-301-451-2761
        • fax_number
        • cell_number+1-301-451-2761
        • email_addressactg.user.support@fstrf.org
        • created2013-12-03 11:41:07
        • modified2020-05-18 15:38:24
  • 2(array)
    • Application(array)
      • id1234
      • user_id21
      • trial_status_id2
      • abstract_of_study<p style=\"margin-left:99.0pt;\">\n <u>DESIGN</u>                   A5356 is a phase II, prospective, randomized, two-arm, open-label, multicenter clinical trial to evaluate the anti-tuberculosis (TB) activity, safety, and tolerability of an injectable-free short course regimen for treatment of multidrug-/rifampicin-resistant (MDR-/RR-), pre-extensively drug-resistant (pre-XDR-), and extensively drug-resistant (XDR-) TB comparing two dosing strategies of linezolid (LZD) combined with bedaquiline (BDQ), delamanid (DLM), and clofazimine (CFZ).</p>\n<p>\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <u>DURATION</u>              72 weeks total: at least 26 weeks (6 months) of anti-TB treatment, with up to 46 weeks of follow-up.</p>\n<p>\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <u>SAMPLE SIZE</u>         132 participants (66 per treatment arm)</p>\n<p>\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <u>POPULATION</u>          Participants aged 18 years and older, with or without HIV, with newly diagnosed pulmonary MDR/RR-TB, pre-XDR-TB, or XDR-TB (collectively noted as DR-TB in the protocol).</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n Participants may be enrolled with a positive rapid diagnostic test for MDR/RR-TB such as Cepheid Xpert MTB/RIF, Cepheid Xpert MTB/RIF Ultra, Hain GenoType MTBDR<em>plus</em>, Hain GenoType MTBDR<em>sl</em>, or other World Health Organization (WHO)-endorsed rapid diagnostic test or with screening phenotypic drug susceptibility testing (DST) from a sputum specimen collected within 60 days prior to entry.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n Participants living with HIV are required to either be on ART or be willing to start ART within 30 days after entry.</p>\n<p>\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <u>REGIMENS</u>              At entry, all participants will be randomized 1:1 to one of two treatment arms (Arm A or Arm B). The only difference in treatment between the two arms is the dosing schedule for LZD, as shown below.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <u>Arm A</u></p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 1-26: LZD 600 mg once daily (QD)</p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 1-2: BDQ 200 mg QD + DLM 300 mg QD + CFZ 300 mg QD</p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 3-8: BDQ 200 mg QD + DLM 300 mg QD + CFZ 100 mg QD</p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 9-26 or -38: BDQ 100 mg QD + DLM 300 mg QD + CFZ 100 mg QD</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <u>Arm B</u></p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 1-4: LZD 1200 mg QD</p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 5-26: LZD 1200 mg three times per week (TIW)</p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 1-2: BDQ 200 mg QD + DLM 300 mg QD + CFZ 300 mg QD</p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 3-8: BDQ 200 mg QD + DLM 300 mg QD + CFZ 100 mg QD</p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 9-26 or -38: BDQ 100 mg QD + DLM 300 mg QD + CFZ 100 mg QD</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n Participants who do not achieve sputum culture conversion by 16 weeks of treatment will extend their treatment by an additional 12 weeks for a total treatment duration of 38 weeks.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n
      • study_title<p align=\"center\">\n A Phase II, Prospective, Randomized, Multicenter Trial to Evaluate the Efficacy and Safety/Tolerability of Two Linezolid Dosing Strategies in Combination with a Short Course Regimen for the Treatment of Drug-Resistant Pulmonary Tuberculosis</p>\n
      • laymans_summary<p>\n This is a research study. Participants who will be  approached regarding this research study will have tuberculosis (TB) that is resistant to some of the drugs generally used to treat it. The purpose of the study is to evaluate the efficacy (how well the medicines work) and tolerability (the level and type of side effects from a drug or treatment) of two different treatment regimens that contain the same four anti-TB medicines: linezolid (LZD), bedaquiline (BDQ), delamanid (DLM), and clofazimine (CFZ). This study will also measure the level of these medicines in your blood.</p>\n<div>\n <div>\n <p>\n Hypothesis;  Linezolid (LZD) administered at an initial dose of 1200 mg daily for 4 weeks followed by 1200 mg three times per week (TIW), plus bedaquiline (BDQ), delamanid (DLM), and clofazimine (CFZ) will be associated with more rapid sputum culture conversion and acceptable rates of treatment discontinuations due to adverse events (AEs), intolerance, and death compared to LZD administered at a dose of 600 mg daily in combination with BDQ, DLM, and CFZ.</p>\n <div>\n The 2 primary objectives are to 1.Compare time to sputum culture conversion in liquid media between treatment arms. And 2 To estimate the occurrence of permanent discontinuation of at least one anti-TB drug due to AEs, intolerance, or death within each treatment arm.</div>\n <p>\n  </p>\n </div>\n <div>\n <div>\n  </div>\n <div>\n <div>\n  </div>\n <div>\n  </div>\n </div>\n </div>\n</div>\n<p>\n  </p>\n
      • short_titleA5356
      • protocol_noECCT/23/05/01
      • version_no1.0
      • date_of_protocol05-04-2021
      • study_drugLinezolid
      • disease_conditionDrug-Resistant Pulmonary Tuberculosis
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameLinezolid
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressviola.kirui@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantFlorence Njulu
      • declaration_date104-05-2023
      • declaration_principal_investigatorAbraham M. Siika
      • declaration_date204-05-2023
      • placebo_presentNo
      • study_objectives<h2>\n  </h2>\n<p>\n <span style=\"font-size:12px;\">   Primary Objectives</span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:times new roman,times,serif;\">1. To compare time to sputum culture conversion in liquid media between treatment arms.</span></span></p>\n<p>\n <span style=\"font-size: 12px;\"><span style=\"font-family:times new roman,times,serif;\">2. To estimate the occurrence of permanent discontinuation of at least one anti-TB drug due to AEs, intolerance, or death within each treatment arm</span>.</span></p>\n<p>\n  Secondary Objectives</p>\n<p>\n 1. To compare proportion with sputum culture conversion in liquid media at 8, 16, 26, and 38 weeks between treatment arms.</p>\n<p>\n 2.To compare permanent discontinuation of LZD due to AEs, intolerance, or death, temporary discontinuation of LZD for any reason, and dose reductions for LZD between treatment arms.</p>\n<p>\n 3. To compare the occurrence of treatment-related AEs between treatment arms.</p>\n<p>\n 4. To compare the occurrence of unfavorable TB treatment outcome at weeks 26, 38 (for those who extend treatment by 12 weeks), and 72 between treatment arms.</p>\n<p>\n 5. To determine LZD pharmacokinetic (PK) parameters for each LZD dosing strategy.</p>\n<p>\n 6.To determine DLM PK parameters within each treatment arm.</p>\n<p>\n 7. To compare adherence to LZD, BDQ, DLM, and CFZ between treatment arms as determined by recording of the number of observed doses based on directly observed therapy (DOT).</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n
      • principal_inclusion_criteria<p style=\"margin-left:72.0pt;\">\n 1    Aged ≥18 years of age at screening.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 2    Newly diagnosed pulmonary drug-resistant TB (DR-TB), with resistance to at least RIF as determined by either genotypic (such as Cepheid Xpert MTB/RIF, Cepheid Xpert MTB/RIF Ultra, Hain GenoType MTBDR<em>plus</em>, Hain GenoType MTBDR<em>sl</em>, or other WHO-endorsed rapid diagnostic test) or with the results of phenotypic drug susceptibility testing (DST) from a sputum specimen collected within 60 days prior to entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE: DR-TB diagnosis for purposes of meeting inclusion criteria can be from a network-approved study testing laboratory or from an outside laboratory.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 3    HIV-1 infection status documented as either absent or present, as defined below:</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n Absence of HIV-1 infection, as documented by any licensed rapid HIV test or HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit, within 60 days prior to entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n OR</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n HIV-1 infection, documented by any licensed rapid HIV test or HIV-1 E/CIA test kit at any time prior to entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load. Two or more HIV-1 RNA viral loads of >1,000 copies/mL are also acceptable as documentation of HIV infection.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE A: The term “licensed” refers to a US FDA-approved kit, which is recommended. For sites that are unable to obtain an FDA-approved kit, a kit that has been certified or licensed by an oversight body within the country and validated internally is acceptable.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE B: WHO and US Centers for Disease Control and Prevention (CDC) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 4    For participants living with HIV, either currently on an ART regimen or willing and able to start ART within 30 days after entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE: For a list of excluded ARV medications, refer to <a href=\"#_APPENDIX_I:_A5356\">Appendix I</a>.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 5    Efavirenz or etravirine must be discontinued prior to a participant’s starting anti‑TB medications. For participants on efavirenz or etravirine, they must be willing and able to discontinue these at least 7 days prior to initiating study TB medications.</p>\n<p style=\"margin-left:36.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 6    For participants living with HIV, CD4+ cell count ≥50 cells/mm³obtained within 60 days prior to study entry at any network-approved non-US laboratory that is Immunology Quality Assurance (IQA) certified. </p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 7    For females of reproductive potential, negative serum or urine pregnancy test within 7 days prior to entry at any network-approved laboratory or clinic that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs.</p>\n<p style=\"margin-left:108.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE: Urine test must have a sensitivity of ≤25 mIU/mL.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 8    Females of reproductive potential who are participating in sexual activity that could lead to pregnancy must agree to use two of the following forms of birth control while receiving TB study medications and for 30 days after stopping study medications:</p>\n<ul>\n <li>\n Male or female condoms</li>\n <li>\n Diaphragm or cervical cap (with spermicide, if available)</li>\n <li>\n Intrauterine device (IUD) or intrauterine system (IUS)</li>\n <li>\n Hormone-based birth control (e.g., oral contraceptives, Depo-Provera, NuvaRing, implants) </li>\n</ul>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE: Females who are not of reproductive potential are eligible without requiring the use of contraceptives. Self-reported history is acceptable documentation of menopause (i.e., at least 1 year amenorrheic), hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; these candidates are all considered not of reproductive potential.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 9    The following laboratory values obtained within 14 days prior to entry at any network-approved laboratory that operates in accordance with Good Clinical Laboratory Practice (GCLP) standards and participates in appropriate external quality assurance programs:</p>\n<ol style=\"list-style-type:lower-alpha;\">\n <li>\n Creatinine ≤1.5 x upper limit normal (ULN)</li>\n <li>\n Absolute neutrophil count (ANC) ≥800/mm³</li>\n <li>\n Hemoglobin level of >8.5 gm/dL for females and >9.0 gm/dL for males </li>\n <li>\n Platelet count ≥100,000 cells/mm³</li>\n <li>\n Alanine aminotransferase (ALT) <2.5 x ULN</li>\n <li>\n Alkaline phosphatase (ALP) <2.5 x ULN; ≥2.5 – 8.0 x ULN <strong>may enroll per the investigator’s discretion after discussion with </strong>the team</li>\n <li>\n Total bilirubin ≤2.0 x ULN, or ≤1.50 x ULN if AST, ALT or ALP is above the ULN but no higher than a Grade 1 level</li>\n <li>\n Potassium level ≥3.4 mEq/L</li>\n <li>\n Negative for HBsAg and HCV antibody</li>\n <li>\n Calculated creatinine clearance (CrCl) >50 mL/min, as estimated by the Cockcroft-Gault equation.</li>\n</ol>\n<p style=\"margin-left:36.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE A: Calculator for the Cockcroft-Gault equation is available at <u>https://www.frontierscience.org/apps/cfmx/apps/common/Portal/index.cfm.</u></p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE B: Any laboratory value that excludes the candidate may be repeated to confirm eligibility. The repeated laboratory value will be excluded from the required >24‑hour window between screening and entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 10  Karnofsky performance score ³50 within 30 days prior to entry.</p>\n<p style=\"margin-left:36.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 11  Ability and willingness of candidate and/or legal guardian/representative to provide informed consent and meet requirements for the study.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 12  Chest X-ray obtained within 30 days prior to entry.</p>\n
      • principal_exclusion_criteria<p style=\"margin-left:72.0pt;\">\n 1    Documentation of clinically significant (as judged by the site investigator) active infections (including HIV-related opportunistic infections) other than TB and HIV requiring treatment within 30 days prior to entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 2    Evidence of clinically significant (as judged by the site investigator) metabolic, gastrointestinal, cardiovascular, musculoskeletal, ophthalmological, pulmonary, neurological, psychiatric, endocrine diseases, malignancy, or other abnormalities (other than the indication being studied) that would interfere with study medications or procedures.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 3    Inability to take oral medications.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 4    Suspected or documented TB involving the central nervous system, clinically significant renal TB or TB pericarditis, or current extrapulmonary TB involving other organ systems that might interfere with study medications or procedures, as judged by the site investigator.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 5    Prior treatment with LZD, DLM, BDQ, or CFZ at any time in the past for an episode of DR-TB that is not the qualifying episode <u>or</u> treatment for more than 7 cumulative days with one or more of LZD, DLM, BDQ, or CFZ within <u>30</u> days prior to entry for the qualifying episode of DR-TB.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE: For the qualifying episode of DR-TB, candidates may receive up to 7 cumulative days of presumptive TB treatment that includes LZD, DLM, BDQ, or CFZ within 30 days prior to entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 6    History of allergy or hypersensitivity to any of the study drugs or medications in the same class as the study drugs.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 7    Known or suspected current alcohol and/or drug abuse that is, in the opinion of the site investigator, sufficient to compromise the safety and/or cooperation of the participant.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 8    Receipt of any investigational drugs within 60 days prior to entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 9    Known history of prolonged QT syndrome or current QTcF interval >450 ms on screening ECG.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 10  Known history of clinically significant cardiac arrhythmia requiring medication or clinically significant ECG abnormality, in the opinion of the site investigator, within 60 days prior to entry, including but not limited to second or third degree atrioventricular (AV) block or prolongation of the QRS complex interval over 120 ms.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 11  Pregnancy or current breastfeeding, or intent to become pregnant and/or breastfeed while on study treatment.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 12  Current use of monoamine oxidase inhibitors or use within 30 days prior to entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 13  Current use of serotonergic agents including SSRI/SNRI antidepressants or prior use within 30 days prior to entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 14  Known history of optic neuropathy of any grade as diagnosed by an ophthalmologist.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 15  Current peripheral neuropathy Grade ≥2.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:36.0pt;\">\n               16  Weight <35 kg.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:36.0pt;\">\n               17 Currently taking other prohibited medications.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE: Refer to <a href=\"#_APPENDIX_I:_A5356\">Appendix I</a> for a list of prohibited medications.</p>\n
      • primary_end_points<h2 style=\"page-break-after:auto\">\n <span lang=\"EN-US\" style=\"font-size: 11pt; font-family: Arial, sans-serif;\">Anticipated Outcomes<o:p></o:p></span></h2>\n<p>\n The pharmacologic evaluations will provide information on the steady-state PK of the LZD, DLM, and other TB regimen components in both study arms. The measures of drug exposure determined from the PK data will be used to evaluate the relationship between the PK parameters achieved in two study arms and study outcomes</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Prof. Abraham M. Siika                                 Site Leader/ Principal Investigator</li>\n <li style=\"line-height: 20px;\">\n Dr. Charity Wamboi                                         Co- Investigator</li>\n <li style=\"line-height: 20px;\">\n Getrude Jerop Kiptoo                                              Study Clinician          </li>\n <li style=\"line-height: 20px;\">\n Vincent KIpchirchir                                                Study Clinician                      </li>\n <li style=\"line-height: 20px;\">\n Philemon Kipchirchir Mutai                                     Study Nurse</li>\n <li style=\"line-height: 20px;\">\n Chris Sande                                                   Study Nurse</li>\n <li style=\"line-height: 20px;\">\n Damaris Lagat                                           Quality Assurance/Control officer</li>\n <li style=\"line-height: 20px;\">\n Shauri Gona                                              Recruitment officer</li>\n <li style=\"line-height: 20px;\">\n Julie Choge                                                     Recruitment officer</li>\n <li style=\"line-height: 20px;\">\n Florence Njulu                                            regulatory Officer</li>\n <li style=\"line-height: 20px;\">\n Wilson Ekiru                                                  Assistant data manger</li>\n <li style=\"line-height: 20px;\">\n Martha Mokaya                                             Data manger           </li>\n <li style=\"line-height: 20px;\">\n Natalie Sang                                         Pharmacist of record</li>\n <li style=\"line-height: 20px;\">\n Beatrice Jakait                                               Backup pharmacist</li>\n <li style=\"line-height: 20px;\">\n Salina Cherutich                                            Pharmaceutical technologist</li>\n <li style=\"line-height: 20px;\">\n Vincent Onyango                                           Phlebotomist</li>\n</ol>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">The outcome of this trial will have major public health implications for areas of the world with high burdens of MDR-TB. The sponsor Country (US) does not fall in this category.</span></p>\n
      • other_details_regulatory_notapproved<p>\n <font color=\"#333333\" face=\"Trebuchet MS, Tahoma, Verdana, Arial, sans-serif\"><span style=\"font-size: 12.5px;\">n/a</span></font></p>\n
      • other_details_regulatory_approved<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Moi Teaching and Referral Hospital/Moi University Institutional Research and Ethics Committee (IREC). Approval granted on 15 December 2022 for the Eldoret site.</span></p>\n
      • other_details_regulatory_rejected<p>\n n/a</p>\n
      • other_details_regulatory_halted<p>\n n/a</p>\n
      • estimated_duration72 weeks
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorbedaquiline, delamanid, c
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaMOI UNIVERSITY CLINICAL RESEARCH CENTRE
      • single_site_physical_addressP.O.BOX 4606-30100
      • single_site_contact_personViola Kirui
      • single_site_telephone+254711729856
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states7
      • number_of_sites
      • multi_country_listSOUTH AFRICA, BRAZIL, BOTSWANA, HAITU, THAILAND, PHILIPINES, PERU
      • data_monitoring_committeeYes
      • total_enrolment_per_siten/a
      • total_participants_worldwide132
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameAbraham
      • investigator1_middle_nameMosigisi
      • investigator1_family_nameSiika
      • investigator1_qualificationMBCHB, MMed, MSc
      • investigator1_professional_addressP O BOX 4606-30100
      • investigator1_telephone+254721280785
      • investigator1_emailabrahamsiika@gmail.com
      • organisations_transferred_No
      • number_participants30
      • notification
      • approval_date06-03-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted04-05-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-03-13 13:13:49
      • created2023-03-07 13:43:59
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id915
        • application_id1234
        • given_nameAbraham
        • middle_nameMosigisi
        • family_nameSiika
        • qualificationMBCHB, MMed, MSc
        • professional_addressP O BOX 4606-30100
        • telephone+254721280785
        • emailabrahamsiika@gmail.com
        • created2023-03-28 10:18:03
        • modified2023-05-04 15:30:25
    • SiteDetail(array)
      • 0(array)
        • id1464
        • application_id1234
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2023-03-28 10:18:03
        • modified2023-05-04 15:30:25
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id652
        • application_id1234
        • sponsorNational Institute of Allergy and Infectious Diseases
        • sponsor_typeOthers
        • contact_personGavin Churchyard, MBBCh, MMed, FRCP, FCP(SA), PhD
        • addressPostnet Suite 300, Private Bag X30500, Houghton, 2041 SOUTH AFRICA
        • telephone_number+27 (0) 10 590 1306
        • fax_number+27 (0) 86 613 3718
        • cell_number+27 (0) 10 590 1306
        • email_addressgchurchyard@auruminstitute.org
        • created2023-03-28 10:18:03
        • modified2023-05-04 15:30:25
  • 3(array)
    • Application(array)
      • id1172
      • user_id781
      • trial_status_id(null)
      • abstract_of_study<p>\n <strong>Introduction - </strong>birth asphyxia remain a leading cause of neonatal mortality and morbidity in Kenya. The primary cause of birth asphyxia is poor perfusion of the fetus by the placenta during labor, which may lead to non-reassuring fetal status (fetal distress), hypoxic injury, or death.  Currently, there are no evidence-based therapies to improve fetal perfusion during labor in cases of severe fetal compromise.  In low-resource settings, intrapartum fetal monitoring may not be available to detect fetal distress and access to urgent operative delivery to relieve distress may be limited.  Feasible therapies for use in low-resource settings to reduce deaths from birth asphyxia are urgently needed.  Sildenafil citrate is a novel approach to reduce fetal distress during labor.  Sildenafil citrate is a phosphodiesterase type-5 inhibitor that acts as a vasodilator that is known to increase uteroplacental blood flow. It is unknown if intrapartum sildenafil citrate would be feasible or effective in low-resource settings. We hypothesize that treatment with sildenafil citrate during labor will decrease stillbirth and early neonatal mortality in low-resource settings, but, first, a feasibility trial to inform the design of a definitive trial appropriate for low-resource settings is necessary.  The specific aims correspond to feasibility objectives that will inform the design and implementation of a large randomized controlled trial of intrapartum sildenafil citrate.</p>\n<p>\n <strong>Objective</strong>: To assess the feasibility of drug administration during early labor, patient acceptance of the intervention, and to confirm the safety of sildenafil citrate in pregnant women in a low-resource setting</p>\n<p>\n <strong>Study design</strong>: Double blinded, placebo-controlled randomized feasibility trial</p>\n<p>\n <strong>Study Setting</strong>; Nakuru county and referral hospital in the Mother and Baby unit</p>\n<p>\n <strong>Methods: </strong>Pregnant women aged 18 to 50years who present to the study health care facilities in early labor will be screened for study eligibility. Eligible women who consent  and if husbands are available have consented for the study will be randomized to receive sildenafil 50 mg orally every 8 hours up to a total of 3 doses or a placebo every 8 hours up to a total of 3 doses during the course of labor. All additional care of the mother and infant will provided according to the local standard of care.  The number and timing of sildenafil doses as well as length of labor in participants will be reported.  The intervention will be considered acceptable if 50% of eligible women enroll.  All enrolled women will be monitored by clinical treatment team for symptoms presenting potential side effects of sildenafil occurring from the time of dose administration to 8 hours following the last dose.  All enrolled neonates will be monitored for neonatal hypoxemia. NICU admission rates in all participants will also be recorded and features of hypoxic ischemic injury will be determined using Sarnat examination. Data will be analyzed using SPSS version 24</p>\n
      • study_title<p align=\"center\">\n <strong>Sildenafil citrate to improve maternal and neonatal outcomes in low-resource settings: </strong></p>\n<p align=\"center\">\n <strong>a randomized feasibility trial</strong></p>\n
      • laymans_summary<p>\n Birth asphyxia, defined by the WHO as failure to establish spontaneous breathing at birth, accounts for nearly 1 million neonatal deaths annually.^1,2  Birth asphyxia is the second most common cause of neonatal mortality worldwide.^1,2The primary cause of birth asphyxia is poor perfusion of the fetus by the placenta during labor, which may lead to non-reassuring fetal status (fetal distress), hypoxic injury, or death.  Currently, there are no evidence-based therapies to improve fetal perfusion during labor in cases of severe fetal compromise.  Urgent operative delivery is the only option to restore gas exchange to the baby.  In low-resource settings, intrapartum fetal monitoring may not be available to detect fetal distress and access to urgent operative delivery to relieve distress may be limited.  Thus, a high burden of death due to birth asphyxia is carried in the developing world. </p>\n<p>\n Feasible therapies for use in low-resource settings to reduce deaths from birth asphyxia are urgently needed.  Sildenafil citrate is a novel approach to reduce fetal distress during labor</p>\n
      • short_titleSildenafil citrate to improve
      • protocol_noECCT/23/05/06
      • version_no1
      • date_of_protocol07-02-2022
      • study_drugSildenafil Citrate
      • disease_conditionBirth asphyxia
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameSildenafil citrate
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamosotara@yahoo.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantAMOS MAGEMBE OTARA
      • declaration_date129-03-2023
      • declaration_principal_investigatorAMOS MAGEMBE OTARA
      • declaration_date229-03-2023
      • placebo_presentYes
      • study_objectives<p>\n <strong>1: To describe the current practices and baseline healthcare provider knowledge regarding fetal heart rate monitoring and indications for operative delivery in a low-resource settings.</strong></p>\n<p>\n <strong>2: To determine the incidence of key maternal and neonatal outcomes that may be targeted in a large definitive trial of intrapartum sildenafil citrate. </strong></p>\n<p>\n <strong>3:To assess the feasibility of drug administration during early labor, patient acceptance of the intervention, and to confirm safety of sildenafil citrate in pregnant women in a low-resource setting.  </strong></p>\n<p>\n  </p>\n
      • principal_inclusion_criteria<ul>\n <li>\n Pregnant women presenting in early labor with a term pregnancy (≥37 weeks gestation)\n <ul>\n <li>\n Early labor will be defined as cervical dilation less than or equal to 6 cm</li>\n <li>\n Gestational age will be calculated from the most reliable variable using the following hierarchy of reliability: 1) gestational dating ultrasound completed at any time during the pregnancy (with preference to the earliest exam), 2) date of last menstrual period if menses are regular</li>\n </ul>\n </li>\n <li>\n Planned vaginal delivery </li>\n <li>\n Maternal age 18-50 years or an emancipated minor according to local standards</li>\n <li>\n A single, live fetus in cephalic presentation confirmed prior to randomization</li>\n</ul>\n
      • principal_exclusion_criteria<ul>\n <li>\n Unknown gestational age</li>\n <li>\n Maternal history of more than 1 prior caesarian delivery</li>\n <li>\n Planned cesarean delivery</li>\n <li>\n Maternal contraindication to sildenafil therapy such as hypersensitivity to nitrates or nitrites</li>\n <li>\n Recognized major fetal anomaly (neurologic, cardiac or pulmonary malformation) or known genetic condition (trisomy)</li>\n <li>\n Any maternal medical condition or status that precludes informed consent</li>\n</ul>\n
      • primary_end_points<p>\n Results of this feasibility trial are an essential first step in the study of sildenafil citrate as a novel treatment to improve fetal status during labor and thus reduce birth asphyxia.  This study, therefore, has the potential to impact one of the most common causes of neonatal mortality worldwide and may alter standard of care of women in labor.   </p>\n<p>\n If this study demonstrates feasibility of intrapartum sildenafil citrate, our team will use the data generated to design a definitive trial.  This study will help to identify the appropriate study outcomes for a trial of sildenafil citrate in a low-resource settings as well as identify any skill or knowledge gaps that require intervention prior to a large trial. </p>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong>The study facility</strong></p>\n<p>\n The 250-bed capacity Margaret Kenyatta Mother Baby Wing at Nakuru Level Five opened by First Lady Margaret Kenyatta in 2018.The Sh450 million state-of-the-art maternity wing is the biggest in the larger Rift Valley region, the largest after Nairobi County’s Pumwani Hospital. It also serves Bomet, Baringo, Narok, Kericho, Samburu, Laikipia and Nyandarua counties. It’s one of the busiest unit in the county with about 1200 deliveries per month. The facility has 3 sections accommodating obstetric cases and one section is been occupied by the gynaecology cases. The unit also has a maternity theatre with two operating and a 24 hour laboratory providing services to the patients in the unit.The facility has a newborn unit with a bed capacity of 50 with facilities to provide continuous positive pressure to neonates with respiratory challenges.</p>\n<p>\n On human resource the maternal   section has 9 obstetrician & gynecologist that man the unit in both the gynecology, obstetric wards and theatre, it has 9 medical officers and at least 4 medical officers interns and 4 clinical officers interns. The newborn units are run by two Paediatricians, one medical officer and at least two medical officers’ interns and two clinical officers’ interns. The whole unit has over 100 nurses with majority of them in the labour ward</p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:60px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:107px;\">\n <p>\n <strong>Name</strong></p>\n </td>\n <td style=\"width:86px;\">\n <p>\n <strong>Project Role</strong></p>\n </td>\n <td style=\"width:116px;\">\n <p>\n <strong>Qualification</strong></p>\n </td>\n <td style=\"width:138px;\">\n <p>\n <strong>Career</strong></p>\n </td>\n <td style=\"width:116px;\">\n <p>\n <strong>Experience</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:60px;\">\n <p>\n 1</p>\n </td>\n <td style=\"width:107px;\">\n <p>\n Dr Amos Otara Magembe</p>\n </td>\n <td style=\"width:86px;\">\n <p>\n Site Coordinator</p>\n </td>\n <td style=\"width:116px;\">\n <p>\n MBChB 1994</p>\n <p>\n M.Med (Obstetrics and Gynaecology) 2000</p>\n </td>\n <td style=\"width:138px;\">\n <p>\n Senior lecturer, Egerton University, Department of Reproductive Health</p>\n <p>\n  </p>\n <p>\n Consultant Obstetrician-Gynaecologist Nakuru County Referral Teaching Hospital</p>\n <p>\n  </p>\n </td>\n <td style=\"width:116px;\">\n <p>\n WHO clinical trial among pregnant women in the county referral hospital e.g.</p>\n <p>\n  </p>\n <p>\n WOMAN Trial 2014</p>\n <p>\n  </p>\n <p>\n Multi-county survey on Maternal and New-born Health 2012</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:60px;\">\n <p>\n 2</p>\n </td>\n <td style=\"width:107px;\">\n <p>\n Dr Elizabeth Gathoni Kibaru</p>\n </td>\n <td style=\"width:86px;\">\n <p>\n Site Investigator</p>\n </td>\n <td style=\"width:116px;\">\n <p>\n MBChB 2001</p>\n <p>\n  </p>\n <p>\n M. Med degree (Pediatrics and child health )2009.</p>\n </td>\n <td style=\"width:138px;\">\n <p>\n Lecturer, Egerton University, Department of Child Health</p>\n <p>\n  </p>\n <p>\n Consultant Pediatrician –Nakuru County and Referral hospital in the Newborn Unit Nakuru.</p>\n <p>\n  </p>\n </td>\n <td style=\"width:116px;\">\n <p>\n Involved in multiple policy implementation studies and WHO clinical trials in Kenya aimed at improving newborn outcome in Nakuru County</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:60px;\">\n <p>\n 3</p>\n </td>\n <td style=\"width:107px;\">\n <p>\n Dr. Rose Jerono Keter</p>\n </td>\n <td style=\"width:86px;\">\n <p>\n Study Pharmacist</p>\n </td>\n <td style=\"width:116px;\">\n <p>\n BPharm</p>\n <p>\n M.Pharm(Clinical Pharmacy)</p>\n </td>\n <td style=\"width:138px;\">\n <p>\n Clinical Pharmacist Nakuru County and Referral hospital in the Newborn Unit Nakuru</p>\n </td>\n <td style=\"width:116px;\">\n <p>\n Studies on Antibiotic Use at NCRH</p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:60px;\">\n <p>\n 4</p>\n </td>\n <td style=\"width:107px;\">\n <p>\n Jeremia Orina</p>\n </td>\n <td style=\"width:86px;\">\n <p>\n Study Nurse</p>\n </td>\n <td style=\"width:116px;\">\n <p>\n KRCHN</p>\n </td>\n <td style=\"width:138px;\">\n <p>\n Nurse Midwive</p>\n </td>\n <td style=\"width:116px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:60px;\">\n <p>\n 5</p>\n </td>\n <td style=\"width:107px;\">\n <p>\n Hellen Nafula</p>\n </td>\n <td style=\"width:86px;\">\n <p>\n Study Nurse</p>\n </td>\n <td style=\"width:116px;\">\n <p>\n KRCHN</p>\n <p>\n Kenya registered Neonatal nurse</p>\n </td>\n <td style=\"width:138px;\">\n <p>\n Neonatology Nurse</p>\n </td>\n <td style=\"width:116px;\">\n <p>\n Working in NBU for the last 11 years</p>\n <p>\n CPAP trainer</p>\n <p>\n Trainer and mentor in NEST project</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:60px;\">\n <p>\n 6</p>\n </td>\n <td style=\"width:107px;\">\n  </td>\n <td style=\"width:86px;\">\n  </td>\n <td style=\"width:116px;\">\n  </td>\n <td style=\"width:138px;\">\n  </td>\n <td style=\"width:116px;\">\n <p>\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The goal of the trial is to determine the impact of sildeafil citrate in resource limited environment.  The sponsors home country, USA, does not meet these criteria.  </p>\n
      • other_details_regulatory_notapproved<p>\n NONE</p>\n
      • other_details_regulatory_approved<p>\n University of Alabama at Birmingham Institutional Review Board, April 2022</p>\n<div>\n  </div>\n<div>\n EGERTON UNIVERSITY ETHICS REVIEW COMMITTEE (EUREC), August 2022</div>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n n/a</p>\n
      • other_details_regulatory_halted<p>\n n/a</p>\n
      • estimated_duration3-6 MONTHS
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorSILDENAFIL AND PLACEBO
      • design_controlled_other_medicinalYes
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaNAKURU COUNTY REFERRAL AND TEACHING HOSPITAL
      • single_site_physical_addressNAKURU COUNTY REFERAL AND TEACHING HOSPITAL
      • single_site_contact_personAMOS OTARA
      • single_site_telephone+254722747470
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site500
      • total_participants_worldwide1000
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenYes
      • subjects_nursing_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameAmos
      • investigator1_middle_nameMagembe
      • investigator1_family_nameOtara
      • investigator1_qualificationMMED. Obstetrics ang Gynaecology
      • investigator1_professional_addressEGERTON UNIVERSITY
      • investigator1_telephone+254722747470
      • investigator1_emailamosotara@yahoo.com
      • organisations_transferred_Yes
      • number_participants500
      • notification
      • approval_date05-07-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted20-09-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe reviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-07-05 10:47:03
      • created2022-09-08 15:44:06
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id850
        • application_id1172
        • given_nameNora
        • middle_name
        • family_nameSwitchenko
        • qualificationMD, Assistant Professor Department of Pediatrics Division of Neonatology
        • professional_address Universityof Alabama at Birmingham
        • telephone860-798-1557
        • emailnswitchenko@uabmc.edu
        • created2022-09-08 16:10:59
        • modified2023-09-20 17:27:32
    • SiteDetail(array)
      • 0(array)
        • id1313
        • application_id1172
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2022-09-08 16:10:59
        • modified2023-09-20 17:27:32
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id604
        • application_id1172
        • sponsorUAB MARY HEERSINK INSTITUTE FOR GLOBAL HEALTH
        • sponsor_typeResearch Institution
        • contact_personPATRICIA M SMITH
        • addressMARY HEERSINK INSTITUTE OF GLOBAL HEALTH AT UAB
        • telephone_number+19024395214
        • fax_number
        • cell_number+19024395214
        • email_addresspmsmith@uabmc.edu
        • created2022-09-08 16:10:59
        • modified2023-09-20 17:27:32
  • 4(array)
    • Application(array)
      • id65
      • user_id34
      • trial_status_id5
      • abstract_of_study<p>\n  </p>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width: 684px;\" width=\"684\">\n <tbody>\n <tr>\n <td style=\"width: 187px; height: 48px;\">\n <p>\n <strong>Design:</strong></p>\n </td>\n <td style=\"width: 497px; height: 48px;\">\n <p>\n An open-label demonstration project to evaluate the safety and effectiveness of the PrePex device for male circumcision in routine Kenyan service delivery sites.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 187px; height: 48px;\">\n <p>\n <strong>Population:</strong></p>\n </td>\n <td style=\"width: 497px; height: 48px;\">\n <p>\n 425 adult men aged 18 to 49 years voluntarily seeking medical male circumcision.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 187px; height: 48px;\">\n <p>\n <strong>Duration:</strong></p>\n </td>\n <td style=\"width: 497px; height: 48px;\">\n <p>\n Approximately 2 months of recruitment plus 42 days of scheduled follow-up per participant; total expected study duration of approximately 4 months in the field.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 187px; height: 47px;\">\n <p>\n <strong>Primary Objective:</strong></p>\n </td>\n <td style=\"width: 497px; height: 47px;\">\n <p>\n To measure rates of moderate and severe adverse events during routine service delivery for PrePex circumcision procedures.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 187px; height: 48px;\">\n <p>\n <strong>Primary Endpoint:</strong></p>\n </td>\n <td style=\"width: 497px; height: 48px;\">\n <p>\n The incidence of moderate and severe adverse events in routine service delivery settings.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 187px; height: 64px;\">\n <p>\n <strong>Secondary Objectives:</strong></p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n <strong>Sites:</strong></p>\n </td>\n <td style=\"width: 497px; height: 64px;\">\n <p>\n The secondary objectives of this research study are to:</p>\n <ul>\n <li>\n Evaluate the acceptability of PrePex procedures among clients and providers in Kenya</li>\n <li>\n Determine the time to complete healing after a PrePex procedure</li>\n <li>\n Determine training needed for proficiency including usefulness of a penis/foreskin training model</li>\n <li>\n Determine costs of PrePex training and service delivery</li>\n <li>\n Document proportion of men ineligible for circumcision with PrePex</li>\n <li>\n Document proportion of men who do not return for removal at 7 days and level of effort and outcomes needed for their active follow-up</li>\n <li>\n Compare outcomes and acceptability in fixed sites versus those served by mobile teams.</li>\n </ul>\n <p>\n  </p>\n <p>\n Fixed clinics with on-site trained staff and sites served by trained mobile teams currently providing routine male circumcision services and able to recruit a total of 425 men within approximately 2 months.</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • study_title<p align=\"center\">\n <strong>Prospective Observational Study of Male Circumcision Using</strong></p>\n<p align=\"center\">\n <strong>the PrePex Device in Routine Clinical Settings in Kenya</strong></p>\n
      • laymans_summary(null)
      • short_title(null)
      • protocol_noECCT/12/11/01
      • version_no1.0
      • date_of_protocol05-10-2012
      • study_drugDevice - PrePex Device for Male Circumcision
      • disease_conditionNone - Adult Male Circumcision
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device1
      • product_type_chemical_name
      • product_type_medical_device_namePrePex Device for Adult Male Circumcision
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressscombes@fhi360.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr. Odoyo June
      • declaration_date123-05-2013
      • declaration_principal_investigatorDr. Peter Cherutich
      • declaration_date223-05-2013
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<p>\n  </p>\n<p>\n All men enrolled in this research study must meet the following inclusion criteria:</p>\n<ul>\n <li>\n Must be aged  18 to 49 years</li>\n <li>\n Must be uncircumcised (on examination)</li>\n <li>\n Must be in good general health</li>\n <li>\n Must agree to voluntary counseling and testing for HIV, or have documentation of testing no more than one week before the MC visit</li>\n <li>\n Must be HIV-uninfected</li>\n <li>\n Must be free of genital ulcerations or other visible signs of STI (on examination)</li>\n <li>\n Must be able to understand study procedures and the requirements of study participation</li>\n <li>\n  Must agree to return to the healthcare facility for the full schedule of follow-up visits after his circumcision or be willing to receive a home visit</li>\n <li>\n Must freely consent to participate in the study and sign a written informed consent form</li>\n <li>\n Must have a cell phone or access to a cell phone</li>\n <li>\n Must agree to provide the study staff with an address, phone number, or other locator information while participating in the research study.</li>\n</ul>\n
      • principal_exclusion_criteria<p>\n  </p>\n<p>\n A man will be excluded from participation in this research study if he has any of the following exclusion criteria:</p>\n<ul>\n <li>\n Penis does not fit any of the five PrePex sizes</li>\n <li>\n Takes a medication that would be a contraindication for elective surgery, such as an anticoagulant or steroid</li>\n <li>\n Has known bleeding/clotting disorder (e.g. hemophilia)</li>\n <li>\n Has an active genital infection, anatomic abnormality (e.g. phimosis or hypospadias) or other disease or condition (e.g. extreme obesity, poorly controlled diabetes, sickle cell anemia, AIDS-like signs or symptoms) which in the investigator’s opinion contraindicates MC or participation in the study</li>\n <li>\n Is participating in another longitudinal biomedical research study.</li>\n</ul>\n
      • primary_end_points<p>\n  </p>\n<p>\n The study will measure the incidence of moderate and severe adverse events (AEs) associated with PrePex procedures, including both procedural and post-procedure events, and all device-related incidents such as dislodgment.  To assure complete ascertainment of AEs, study-specific forms will be used to collect standardized data from the circumcision visit and all follow-up visits.  Follow-up will be more intensive for the first 50 cases, and will revert to routine practice (two follow-up visits) for the remaining 375 cases.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyThe secondary objectives of this research study are as follows:\n1) Evaluate the acceptability of PrePex procedures among Kenyan clients and providers.\n2) Determine the time to complete healing after PrePex procedures.\n3) Determine training needed for proficiency. \n4) Determine costs of PrePex training and service delivery.\n5) Document proportion of men ineligible for circumcision with PrePex.\n6) Document proportion of men who do not return for removal at 7 days, and the level of effort needed for their active follow-up as well as their outcomes.\n7) Compare outcomes and acceptability in fixed sites versus those served by mobile teams. \n
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifysafety
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n <strong>Staff Names and Qualifications</strong>:</p>\n<p>\n Elijah Odoyo-June, MBChB, 3 years of experience in MMC Research</p>\n<p>\n Walter Obiero, MBChB, 5 years of experience in MMC Research</p>\n<p>\n Felix Opiyo Aoya, Diploma in Clinical Medicine, 9 years of experience in MMC Research</p>\n<p>\n Valentine Odhiambo Pengo, Diploma in Clinical Medicine, 5 years of experience in MMC Research</p>\n<p>\n Maurice Onyango, Diploma in Community Health Nursing, 10 years of experience in MMC Research</p>\n<p>\n Betha Ochomo, Diploma in Community Health Nursing, 3 years of experience in MMC Research</p>\n<p>\n Godfrey Owino Ajwang, Higher diploma in Psychological Counseling, 5 years of experience in MMC Research</p>\n<p>\n Lillian Jumba, B.A. in Counseling,  5 years of experience in MMC Research</p>\n<p>\n James Aggrey Ogollah, MPH, 10 years of experience in MMC Research</p>\n<p>\n Virginia Akach, Diploma in Public Relations, 8 years of experience in MMC Research</p>\n<p>\n Millicent Akello, Diploma in Human Resource Management, 7 years of experience in MMC Research</p>\n<p>\n Rosemary Achieng Onyango, B.A.in Sociology & Anthropology, 10 years of experience in MMC  Research</p>\n<p>\n Merab Akinyi Ndinya, Ceritificate in Social Work & Community Development, 10 years of experience in MMC Research</p>\n<p>\n Rachel Awino Okune, Certificate in General Counseling, 8 years of experience in MMC Research</p>\n<p>\n Rippon Akoth, Diploma in Purchase & Supplies, 5 years of experience in MMC Research</p>\n<p>\n Monica Knote, Certificate in IT, 3 years of experience in MMC Research</p>\n<p>\n Cleophas Omondi Gumba, Certificate in Psychological Counseling, 6 years of experience in MMC Research</p>\n<p>\n John Adwera, Web based courses, 7 years of experience in MMC Research</p>\n<p>\n George Agal, Diploma in Community Health, 5 years of experience in MMC Research</p>\n<p>\n Maurice Orao Osome, Driver, 10 years of experience in MMC Research</p>\n<p>\n George Ogano, Diploma in Mechanics, 9 years of experience in MMC Research</p>\n<p>\n  </p>\n<p>\n <strong>Facility</strong>:  UNIM/Nyanza Reproductive Health Society, P.O. Box 1764, Kisumu, KENYA</p>\n<p>\n <strong>Study Area</strong>:  Kisumu and Rachuonyo</p>\n
      • other_details_explanation<p>\n At request of the Government of Kenya.</p>\n
      • other_details_regulatory_notapproved<p>\n N/a</p>\n
      • other_details_regulatory_approved<p>\n n/a</p>\n
      • other_details_regulatory_rejected<p>\n n/a</p>\n
      • other_details_regulatory_halted<p>\n n/a</p>\n
      • estimated_duration1 year
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaThe Nyanza Reproductive Health Society UNIM clinic in Kisumu with assistance from NRHS’s mobile outreach service providers in Rachuonyo.
      • single_site_physical_addressUnited Mall, Kisumu
      • single_site_contact_personDr. Odoyo June
      • single_site_telephone254 57 2024065
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_siteN/A
      • total_participants_worldwideN/A
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female0
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_namePaul
      • investigator1_middle_name
      • investigator1_family_nameFeldblum
      • investigator1_qualificationPhD
      • investigator1_professional_address2224 E NC Highway 54, Durham, NC 27713 USA
      • investigator1_telephone+19195447040
      • investigator1_emailpfeldblum@fhi360.org
      • organisations_transferred_No
      • number_participants425
      • notification
      • approval_date02-11-2012
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted07-06-2013
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2014-02-20 20:56:43
      • created2013-03-15 21:24:45
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id41
        • application_id65
        • given_nameRobert
        • middle_name
        • family_nameBailey
        • qualificationPhD, MPH
        • professional_addressSchool of Public Health, University of Illinois at Chicago, 1603 West Taylor Street, Chicago, IL, USA
        • telephone+1312-355-0440
        • emailrcbailey@uic.edu
        • created2013-03-15 21:28:54
        • modified2013-06-07 22:31:14
      • 1(array)
        • id42
        • application_id65
        • given_namePeter
        • middle_name
        • family_nameCherutich
        • qualificationMBChB, MPH
        • professional_addressNational AIDS/STD Control Programme (NASCOP), Ministry of Public Health & Sanitation, P.O Box 19361-00202, Nairobi, KENYA
        • telephone +254 20 272 9502
        • emailpcheru@nascop.or.ke
        • created2013-03-15 21:46:04
        • modified2013-06-07 22:31:14
      • 2(array)
        • id43
        • application_id65
        • given_nameWalter
        • middle_name
        • family_nameObiero
        • qualificationMBChB, MPH, MS
        • professional_addressNyanza Reproductive Health Society, P.O. Box 1764, Kisumu, KENYA
        • telephone +254 733 999 099
        • emailwobiero@nrhskenya.org
        • created2013-03-15 21:46:04
        • modified2013-06-07 22:31:14
      • 3(array)
        • id44
        • application_id65
        • given_nameElijah
        • middle_name
        • family_nameOdoyo June
        • qualificationMBChB, MPH
        • professional_addressNyanza Reproductive Health Society, P.O. Box 1764, Kisumu, KENYA
        • telephone+254 710 848 484
        • emailjodoyo@nrhskenya.org
        • created2013-03-15 21:46:04
        • modified2013-06-07 22:31:14
    • SiteDetail(array)
      • 0(array)
        • id58
        • application_id65
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2013-03-15 21:28:54
        • modified2013-06-07 22:31:14
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id33
        • application_id65
        • sponsorFHI 360 (formerly, Family Health International)
        • sponsor_type(null)
        • contact_personPaul Feldblum
        • address2224 E NC Highway 54, Durham, NC 27713, USA
        • telephone_number+1-919-544-5040 x11237
        • fax_number
        • cell_number+1-919-452-2901
        • email_addresspfeldblum@fhi360.org
        • created2013-03-15 21:28:54
        • modified2013-06-07 22:31:14
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(empty)
• $this->validationErrors(array)
  • Permission(empty)
  • Aro(empty)
  • Aco(empty)
  • Application(empty)
  • User(empty)
  • TrialStatus(empty)
  • InvestigatorContact(empty)
  • Sponsor(empty)
  • SiteDetail(empty)
  • County(empty)
• Loaded Helpers(array)
  • 0Html
  • 1Form
  • 2Session
  • 3Text
  • 4Number
  • 5SimpleGraph
  • 6Paginator
  • 7DebugTimer
  • 8Toolbar
  • 9HtmlToolbar

App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

• 0/var/www/html/ctr/app/Plugin/Media/Lib/mm/src
• 1/var/www/html/ctr/lib
• 3/usr/share/php
• 4-> /var/www/html/ctr/lib/Cake/

Included Files

• core(array)
  • Behavior(array)
    • 0CORE/Model/Behavior/TreeBehavior.php
    • 1CORE/Model/Behavior/ContainableBehavior.php
    • 2CORE/Model/Behavior/AclBehavior.php
  • Cache(array)
    • 0CORE/Cache/Cache.php
    • 1CORE/Cache/Engine/FileEngine.php
    • 2CORE/Cache/CacheEngine.php
  • Component(array)
    • 0CORE/Controller/Component/AclComponent.php
    • 1CORE/Controller/Component/Acl/DbAcl.php
    • 2CORE/Controller/Component/Acl/AclInterface.php
    • 3CORE/Controller/Component/AuthComponent.php
    • 4CORE/Controller/Component/RequestHandlerComponent.php
    • 5CORE/Controller/Component/SessionComponent.php
    • 6CORE/Controller/Component/PaginatorComponent.php
  • Config(array)
    • 0CORE/Config/routes.php
    • 1CORE/Config/config.php
  • Controller(array)
    • 0CORE/Controller/Controller.php
    • 1CORE/Controller/ComponentCollection.php
    • 2CORE/Controller/Component.php
  • Datasource(array)
    • 0CORE/Model/Datasource/CakeSession.php
    • 1CORE/Model/Datasource/Database/Mysql.php
    • 2CORE/Model/Datasource/DboSource.php
    • 3CORE/Model/Datasource/DataSource.php
  • Error(array)
    • 0CORE/Error/exceptions.php
    • 1CORE/Error/ErrorHandler.php
  • I18n(array)
    • 0CORE/I18n/I18n.php
    • 1CORE/I18n/L10n.php
  • Log(array)
    • 0CORE/Log/CakeLog.php
    • 1CORE/Log/LogEngineCollection.php
    • 2CORE/Log/Engine/FileLog.php
    • 3CORE/Log/Engine/BaseLog.php
    • 4CORE/Log/CakeLogInterface.php
  • Model(array)
    • 0CORE/Model/ConnectionManager.php
    • 1CORE/Model/Permission.php
    • 2CORE/Model/Model.php
    • 3CORE/Model/BehaviorCollection.php
    • 4CORE/Model/Aro.php
    • 5CORE/Model/AclNode.php
    • 6CORE/Model/Aco.php
    • 7CORE/Model/ModelBehavior.php
  • Network(array)
    • 0CORE/Network/CakeRequest.php
    • 1CORE/Network/CakeResponse.php
  • Other(array)
    • 0CORE/bootstrap.php
    • 1CORE/basics.php
    • 2CORE/Core/App.php
    • 3CORE/Core/Configure.php
    • 4CORE/Core/CakePlugin.php
    • 5CORE/Event/CakeEventListener.php
    • 6CORE/Event/CakeEvent.php
    • 7CORE/Event/CakeEventManager.php
    • 8CORE/Core/Object.php
  • Routing(array)
    • 0CORE/Routing/Dispatcher.php
    • 1CORE/Routing/Filter/AssetDispatcher.php
    • 2CORE/Routing/DispatcherFilter.php
    • 3CORE/Routing/Filter/CacheDispatcher.php
    • 4CORE/Routing/Router.php
    • 5CORE/Routing/Route/CakeRoute.php
    • 6CORE/Routing/Route/PluginShortRoute.php
  • Utility(array)
    • 0CORE/Utility/Hash.php
    • 1CORE/Utility/Inflector.php
    • 2CORE/Utility/ObjectCollection.php
    • 3CORE/Utility/Debugger.php
    • 4CORE/Utility/String.php
    • 5CORE/Utility/ClassRegistry.php
    • 6CORE/Utility/Set.php
    • 7CORE/Utility/Sanitize.php
  • View(array)
    • 0CORE/View/HelperCollection.php
• app(array)
  • Behavior(array)
    • 0APP/Model/Behavior/SoftDeleteBehavior.php
  • Config(array)
    • 0APP/Config/core.php
    • 1APP/Config/bootstrap.php
    • 2APP/Config/routes.php
    • 3APP/Config/database.php
  • Controller(array)
    • 0APP/Controller/ApplicationsController.php
    • 1APP/Controller/AppController.php
  • Model(array)
    • 0APP/Model/AppModel.php
    • 1APP/Model/Application.php
    • 2APP/Model/User.php
    • 3APP/Model/TrialStatus.php
    • 4APP/Model/InvestigatorContact.php
    • 5APP/Model/Sponsor.php
    • 6APP/Model/SiteDetail.php
    • 7APP/Model/County.php
  • Other(array)
    • 0APP/webroot/index.php
• plugins(array)
  • CakePdf(array)
    • Config(array)
      • 0CakePdf/Config/bootstrap.php
      • 1CakePdf/Config/routes.php
  • CakeResque(array)
    • Config(array)
      • 0CakeResque/Config/bootstrap.php
    • Plugin(array)
      • 0CakeResque/Lib/CakeResque.php
      • 1CakeResque/vendor/kamisama/php-resque-ex/lib/Resque.php
      • 2CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Event.php
      • 3CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Exception.php
  • DebugKit(array)
    • Component(array)
      • 0DebugKit/Controller/Component/ToolbarComponent.php
    • Plugin(array)
      • 0DebugKit/Lib/DebugMemory.php
      • 1DebugKit/Lib/Panel/HistoryPanel.php
      • 2DebugKit/Lib/DebugPanel.php
      • 3DebugKit/Lib/Panel/SessionPanel.php
      • 4DebugKit/Lib/Panel/RequestPanel.php
      • 5DebugKit/Lib/Panel/SqlLogPanel.php
      • 6DebugKit/Lib/Panel/TimerPanel.php
      • 7DebugKit/Lib/Panel/LogPanel.php
      • 8DebugKit/Lib/Log/Engine/DebugKitLog.php
      • 9DebugKit/Lib/Panel/VariablesPanel.php
      • 10DebugKit/Lib/Panel/EnvironmentPanel.php
      • 11DebugKit/Lib/Panel/IncludePanel.php
      • 12DebugKit/Lib/DebugTimer.php
  • Media(array)
    • Config(array)
      • 0Media/Config/bootstrap.php
    • Plugin(array)
      • 0Media/Lib/mm/src/Mime/Type.php
      • 1Media/Lib/mm/src/Mime/Type/Magic/Adapter/Fileinfo.php
      • 2Media/Lib/mm/src/Mime/Type/Magic/Adapter.php
      • 3Media/Lib/mm/src/Mime/Type/Glob/Adapter/Memory.php
      • 4Media/Lib/mm/src/Mime/Type/Glob/Adapter.php
      • 5Media/Lib/mm/src/Media/Process.php
      • 6Media/Lib/mm/src/Media/Info.php
  • Search(array)
    • Component(array)
      • 0Search/Controller/Component/PrgComponent.php
    • Behavior(array)
      • 0Search/Model/Behavior/SearchableBehavior.php
  • Shim(array)
    • Config(array)
      • 0Shim/Config/bootstrap.php
  • Tools(array)
    • Config(array)
      • 0Tools/Config/bootstrap.php