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  • 1Recruiting
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• applications(array)
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    • Application(array)
      • id554
      • user_id640
      • trial_status_id1
      • abstract_of_study<p>\n This is a Phase II, open label, single arm trial to evaluate the pharmacokinetics, safety, tolerability and efficacy of rilpivirine (RPV, previously known as TMC278) 25 mg once daily (q.d.) or an adjusted dose of RPV (q.d.) in combination with an investigator-selected background regimen containing 2 nucleoside/nucleotide reverse transcriptase inhibitors</p>\n<p>\n (N[t]RTIs) (zidovudine [AZT], abacavir [ABC], or tenofovir disoproxil fumarate [TDF] in combination with lamivudine [3TC] or emtricitabine [FTC], whichever is approved and marketed or considered local standard of care) in antiretroviral (ARV) treatment-naïve adolescents and children aged ≥ 6 to <18 years.</p>\n<p>\n The trial will consist of a screening period of maximum 8 weeks, an initial treatment period of 48 weeks, and a post Week 48 treatment extension period of 4 years. Subjects who withdraw from the trial on or before the Week 48 visit or subjects with ongoing (serious) adverse events ([S]AEs) at the last on-treatment visit in the extension, will be seen for a follow-up visit 4 weeks later. Recruitment and analyses of the initial 48-week treatment period will be structured into 2 age cohorts: Cohort 1, adolescents ≥12 to <18 years of age; Cohort 2, children ≥6 to <12 years of age.</p>\n
      • study_title<div>\n <strong>A Phase II, open label, single arm trial to evaluate the pharmacokinetics, safety, tolerability, and antiviral activity of rilpivirine (TMC278) in antiretroviral-naïve HIV-1 infected adolescents and children aged ≥6 to <18 years</strong></div>\n
      • laymans_summary(null)
      • short_titlePAINT Study
      • protocol_noECCT/16/10/02
      • version_noClinical Trial Protocol Amendment 7.0
      • date_of_protocol18-12-2015
      • study_drugrilpivirine hydrochloride
      • disease_conditionHIV
      • 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_nameEDURANT®
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressnkisengese@yahoo.co.uk
      • applicant_covering_letter1
      • applicant_protocol1
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      • applicant_approval_letter0
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      • applicant_participating_countries1
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      • applicant_stability_data(null)
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      • applicant_pictorial_sample(null)
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      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantNicodemus Ivuti Kisengese
      • declaration_date126-10-2016
      • declaration_principal_investigatorProfessor Walter Jaoko, KAVI Institute of Clinical Research, College of Health Sciences, University of Nairobi
      • declaration_date226-10-2016
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<div>\n Subjects who meet all of the following criteria are eligible for this trial:</div>\n<ol>\n <li>\n Cohort 1: Boys or girls, aged ≥12 to <18 years. Cohort 2: Boys or girls, aged ≥6 to <12 years.</li>\n <li>\n Cohort 1: Subject’s weight is ≥32 kg.Cohort 2: Subject’s weight is ≥17 kg.</li>\n <li>\n Subject with documented chronic HIV-1 infection.</li>\n <li>\n Subject willing and able to give consent. In case the subject’s age is below the cut-off age for consent (according to local regulations), their parent/caregiver should be able and willing to give consent, and the subject will be informed about the trial and asked to give positive assent.</li>\n <li>\n Subject can comply with the protocol requirements.</li>\n <li>\n Subject has, prior to screening, never been treated with a therapeutic HIV vaccine or an HIV drug with the exception of a single dose of NVP (Cohort 1) or up to 6 weeks of AZT use (Cohort 2) to prevent MTCT.</li>\n <li>\n HIV-1 plasma viral load at screening ≥500 HIV-1 RNA copies/mL but ≤100,000 HIV-1 RNA copies/mL (assayed by RNA polymerase chain reaction [PCR] standard specimen procedure).  <u>Note</u>: For Cohort 1 Part 1a, subjects with a screening viral load ≥5,000 HIV-1 RNA copies/mL were allowed.<u>  Note:</u> To reassess eligibility, retesting of a screening value that leads to exclusion will be allowed only once during the screening period using an unscheduled visit.</li>\n <li>\n In the judgment of the investigator, it is appropriate to initiate ART based on the subject’s medical condition and taking into account guidelines for the treatment of HIV-1 infection in children of this age group. <u>Note:</u> Most current treatment guidelines recommend considering initiation of ART when CD4+ cell counts are <350 cells/mm³. However, clinical situations may warrant initiating ART with CD4+ cell counts >350 cells/mm³. An example of such situations would include rapidly declining CD4+ cell counts over time.</li>\n <li>\n Results from the screening HIV-1 genotype demonstrate sensitivity to the selected N(t)RTIs.</li>\n <li>\n Subject is able to swallow the RPV tablet as a whole (since the tablet cannot be chewed, broken, or crushed), except when the appropriate RPV dose for the subjects is determined to be <25 mg (only applicable for subjects enrolled after it has been decided that a lower RPV dose is appropriate for subjects up to a certain e.g., age or body weight). In this case an age-appropriate formulation other than the tablet formulation will be provided.</li>\n <li>\n The subject agrees (or their parents/caregivers agree, in case the subject's age is below the cut-off age for consent according to local regulations, in which case the subject is informed and asked to give positive assent) not to start ART before the baseline visit.</li>\n <li>\n General medical condition, in the investigator’s opinion, does not interfere with the assessments and the completion of the trial.</li>\n</ol>\n
      • principal_exclusion_criteria<div>\n Any previous use of ARVs, with the exception of a single dose of NVP (Cohort 1) or up to 6 weeks of AZT use (Cohort 2) to prevent MTCT.</div>\n<div>\n Note: Cohort 1: Subjects who were infected by MTCT are allowed to enter, provided the mother was ARV treatment-naïve at the time of delivery with the exception of</div>\n<div>\n NVP for no more than 3 days.</div>\n
      • primary_end_points<div>\n <span style=\"font-size:14px;\"><strong>Efficacy</strong></span></div>\n<div>\n  </div>\n<div>\n <u>Plasma viral load</u></div>\n<div>\n Throughout the analysis, plasma viral load will be log10 transformed. Plasma viral load reported as <50 HIV-1 RNA copies/mL will be scored as 49 HIV-1 RNA copies/mL, if not otherwise mentioned.</div>\n<div>\n  </div>\n<div>\n <u>Parameters for Part 1:</u></div>\n<ul>\n <li>\n The change in plasma viral load from baseline at Week 2 (Cohort 1 Part 1a, Cohort 2)/Week 4 (Cohort 1 Part 1b).</li>\n</ul>\n<div>\n  </div>\n<div>\n <u>Parameters for Part 2:</u></div>\n<ul>\n <li>\n Proportion of subjects with a viral load <50 and <400 HIV-1 RNA copies/mL at all time points, and time to achieve these;</li>\n <li>\n Proportion of subjects with a decrease from baseline in plasma viral load of 1.0 log10 at Week 12</li>\n <li>\n Change from baseline in log10 viral load;</li>\n <li>\n Time to loss of response.</li>\n</ul>\n<div>\n <span style=\"font-size:14px;\"><strong>Immunology</strong></span></div>\n<div>\n  </div>\n<div>\n <u>Immunology parameter:</u></div>\n<ul>\n <li>\n The change from baseline in CD4+ cell count (absolute and %).</li>\n</ul>\n<div>\n The analysis will be based on observed values and on imputed values using NC = F, i.e., subjects who prematurely discontinued the trial and will have their CD4+ cell count following discontinuation imputed with the baseline value (resulting in a change of 0), and will have LOCF for intermediate missing values.</div>\n<div>\n  </div>\n<div>\n Raw data and changes versus baseline will be descriptively and graphically presented.</div>\n<div>\n  </div>\n<div>\n <u>Resistance Determinations</u></div>\n<div>\n The results of the viral pheno- and genotypes will be evaluated by the Protocol Virologist. Relevant changes in the viral phenotype and genotype will be tabulated and described, particularly for subjects with virologic failure. These changes in viral phenotype and genotype will not be regarded as AEs.</div>\n<div>\n  </div>\n<div>\n Furthermore, phenotypic resistance data, including the fold change in EC50 values, of RPV and other ARVs will be described.</div>\n<div>\n  </div>\n<div>\n <div>\n  </div>\n <div>\n <strong>Safety</strong></div>\n <div>\n  </div>\n <div>\n <u>Adverse Events/HIV-Related Events</u></div>\n <div>\n Type (system organ class, preferred term) and incidence of all AEs and HIV-related events, between the signing of ICF and last trial-related activity, will be tabulated per trial period (i.e., screening, the treatment period and follow-up). Separate tabulations will be made by severity, drug relationship, and outcome of the AEs. Separate tabulations and listings will be made for those subjects who have discontinued the trial for an AE/HIV-related event, or who experienced a grade 3r 4 AE, or an SAE.</div>\n</div>\n<div>\n  </div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • 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_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n This study will be conducted at Kenyatta National Hospital Comprehensive Care Centre (CCC) and at KAVI-Institute of Clinical Research at the University of Nairobi. The two are about 500 metres apart. All the clinical and laboratory work will be conducted at the CCC, while data entry, study monitoring, financial oversight and overall clinical trial management will be provided by KAVI-Institute of Clinical Research. KAVI has a Data Entry Centre with 5 desktop computers with high speed internet connectivity with a personnel consisting of a Data Manager, and 4 Data Entry Clerks, and a well established financial management system managed by a Finance Manager, a Deputy Finance Manager and an Accounts Assistant. The clinical trial monitoring will be performed by KAVI-ICR Internal Monitor. The Principle Investigator will provide the oversee the overall clinical trials management of the trial.</p>\n
      • other_details_explanation<p>\n The trial is conducted in five countries across Africa, USA and Asia. This is to collect more data across different geographic regions.</p>\n
      • other_details_regulatory_notapproved<p>\n There is no regulatory authority that has not granted approval to this study</p>\n<p>\n This stduy has received full ethical approval from Kenyatta National Hospital Ethics Review Committee.</p>\n
      • other_details_regulatory_approved<p>\n Uganda National Council for Science and Technology  has approved 2 sites</p>\n<p>\n Thailand Ministry of Health has approved one site </p>\n<p>\n South Africa Medicines Control Council has approved 3 sites </p>\n<p>\n United States of America has approved 2 sites</p>\n<p>\n India drug regulatory authority has approved one site </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_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_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states5
      • number_of_sites2
      • multi_country_listUSA\nThailand\nKenya\nUganda\nSouth Africa
      • data_monitoring_committeeYes
      • total_enrolment_per_site6-12
      • total_participants_worldwide56
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18No
      • 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_nameProfessor Walter
      • investigator1_middle_name
      • investigator1_family_nameJaoko
      • investigator1_qualificationMBChB, MTropMed, PhD, PGD (Health Research Ethics)
      • investigator1_professional_addressDepartment of Medical Microbiology, University of Nairobi; P.O Box 19676 Nairobi-00202, Kenya
      • investigator1_telephoneTel: +254 727 555 254
      • investigator1_emailWJaoko@kaviuon.org
      • organisations_transferred_No
      • number_participants6-12
      • notification<p>\n The follwoing dpcuments have been provided as hard copies because they are size is more than allowable to be attached on this portal. </p>\n<ol>\n <li>\n Investigational Material Packaging Agreement version 28 dated 26 May 2016</li>\n <li>\n Rilpivirine Hydrochloride Safety Data Sheet version 1.92, 05 July 2016</li>\n <li>\n Rilpivirine Hydrochloride dispersible tablets 2.5 mg Certificate of Analysis signed 07 September 2015</li>\n <li>\n Rilpivirine (TMC278) granules 2.5mg/gram Certificate of Analysis, approved 30 December 2013</li>\n <li>\n Study Adherence Questionnaire Care Givers addendum 8, version 3.0, 01 Dec 2015 - Swahili version Kenya dated 18 Dec 2015</li>\n <li>\n Study Adherence Questionnaire Care Givers, addendum 8, English version 3.0, 01 December 2015</li>\n <li>\n Study Adherence Questionnaire Child version 2.0 23 May 2012 - Swahili Final version dated 18 Dec 2015</li>\n <li>\n Study Adherence Questionnaire Subject English version 2.0 23 May 2012</li>\n <li>\n Child Trial Map (Swahili version 1.1 08 OCT 2015)</li>\n <li>\n  Child Trial Map (English  version 1.0 08 OCT 2015)</li>\n <li>\n Patient and Parent Information Booklet Swahili version 5.0 08 OCT 2015</li>\n <li>\n Patient and Parent Information Booklet English version 5.0 08 OCT 2015</li>\n <li>\n TMC278TiDP38C213-SWA21 INT-7 Patient and Parent Information Booklet Swahili Version 1.0, 18DEC2015</li>\n <li>\n TMC278TiDP38C213-SWA21 INT-7 Patient and Parent Information Booklet English Version 1.0, 18DEC2015</li>\n <li>\n Medication Diary ( Swahili version 4.0 08 OCT 2015)</li>\n <li>\n Medication Diary ( English  version 4.0 08 OCT 2015)</li>\n <li>\n Taste Test English Version  1.0, 10 Sep 2015</li>\n <li>\n Taste Test Swahili Version  1.0, 23 Nov 2015</li>\n <li>\n Appointment Card English Version 1.0, 09-Sep-2015</li>\n <li>\n Visit completion certificates English version 1.0, 09 Sep 2015</li>\n <li>\n  Birthday Cards English V1.0, 09-Sep-2015</li>\n <li>\n  Subject Emergency Card version 1.0 06 Jul 2011</li>\n <li>\n Picture of Crayons (Swahili version)</li>\n <li>\n Picture of Crayons (English version)</li>\n <li>\n Instructions on how to prepare the study medication at home (<em>Rilpivirine dispersible tablet</em>) version 1.0 dated 10 May 2016 (English and Swahili)</li>\n</ol>\n
      • approval_date13-02-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted27-10-2016
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
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      • quantity_imported(null)
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      • quantity_destroyed(null)
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      • balance_site(null)
      • final_date(null)
      • modified2020-09-23 08:46:56
      • created2016-09-05 10:54:23
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id356
        • application_id554
        • given_nameProfessor Walter
        • middle_name
        • family_nameJaoko
        • qualificationMBChB, MTropMed, PhD, PGD (Health Research Ethics)
        • professional_addressDepartment of Medical Microbiology, University of Nairobi; P.O Box 19676 Nairobi-00202, Kenya
        • telephoneTel: +254 727 555 254
        • emailWJaoko@kaviuon.org
        • created2016-09-05 11:12:41
        • modified2016-10-27 10:54:51
    • SiteDetail(array)
      • 0(array)
        • id431
        • application_id554
        • county_id47
        • site_nameKAVI Institute of Clinical Research
        • physical_addressDepartment of Medical Microbiology,College of Health Sciences University of Nairobi
        • contact_detailsP.O Box 19676 Nairobi-00202, Kenya Tel: +254 727 555 254
        • contact_personProfessor Walter Jaoko
        • site_capacity(null)
        • misc(null)
        • created2016-09-05 11:12:41
        • modified2016-10-27 10:54:51
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id444
        • application_id554
        • county_id35
        • site_nameKenya Medical Research Institute/Walter Reed Project, HIV Program
        • physical_addressHospital Road, Kericho, Kenya
        • contact_detailsP.O Box 1357 - 20200, Hospital Road, Kericho, Kenya Tel: +254 52 30686/+254 52 30388 Mobile: +254 729110124 Fax: +254 52 30662/+254 52 30546
        • contact_personDr. Isaac Tsikhutsu, MBChB, MMED, FPCCM
        • site_capacity(null)
        • misc(null)
        • created2016-10-27 07:08:06
        • modified2016-10-27 10:54:51
        • County(array)
          • id35
          • county_nameKericho
          • created2012-06-15 10:26:16
          • modified2012-06-15 10:26:16
    • Sponsor(array)
      • 0(array)
        • id284
        • application_id554
        • sponsorJanssen Research and Development
        • sponsor_type(null)
        • contact_personLinda Roach
        • addressBuilding 6, Country Club Estates 21 Woodlands Drive Woodmead, 2191, South Africa.
        • telephone_number+27 11 518 7173
        • fax_number+27 11 518 7102/3
        • cell_number+27 71 622 2242 .
        • email_addresslroach@its.jnj.com
        • created2016-09-05 11:12:41
        • modified2016-10-27 10:54:51
  • 1(array)
    • Application(array)
      • id552
      • user_id345
      • trial_status_id1
      • abstract_of_study<p>\n <span style=\"font-size:14px;\"><strong><u>INVICTUS TRIALS: INVESTIGATION OF RHEUMATIC AF TREATMENT USING VITAMIN K ANTAGONISTS, RIVAROXABAN OR ASPRIN STUDIES</u></strong></span><br />\n  </p>\n<p style=\"text-align: justify;\">\n <span style=\"font-size:14px;\"><u>BACKGROUND:</u><br />\n In developing countries, AF, a common cardiac arrhythmia is related to rheumatic valvular heart disease (RVHD) especially mitral valve disease. With AF, the risk of stroke increases by a facroe of 5 and is reponsible for up to 20% of the stroke events. Vitamin K antagonists(VKA) have been established as effective for prevention of stroke in AF. Apsrin has been found to be less effective than VKA. However VKAs are limited by multiple drug interactions and inter-patient variabilities necessitating the need for frequent monitoring of the coagulation status to optimize efficacy and safety. This poses a challenge in developing nations. Rivaroxaban has been documented as effective in prevention of stroke in AF without the need for frequent monitoring of the coagulation status. INVICTUS trials are designed to address the need to establish the safety and efficacy of rivaroxaban for prevention of stoke in rheumatic AF.</span><br />\n <br />\n  </p>\n<div>\n <span style=\"font-size:14px;\"><u><strong>Primary Hypotheses</strong></u></span></div>\n<div>\n <span style=\"font-size:14px;\">1. In patients with rheumatic valvular heart disease (RVHD) and who are in atrial fibrillation or flutter (AF/flutter) and have other stroke risk factors, rivaroxaban is non-inferior to vitamin K antagonists (VKAs) for prevention of stroke or systemic embolism.</span></div>\n<div>\n <span style=\"font-size:14px;\">2. In patients with RVHD, either with AF/flutter but unsuitable for VKA therapy, or with sinus rhythm but with high risk, rivaroxaban is superior to aspirin for prevention of stroke or systemic embolism. Study Design</span></div>\n<div>\n <span style=\"font-size:14px;\">This program is a comprehensive evaluation of RVHD, AF/flutter and stroke. It includes three major components:</span></div>\n<div>\n <span style=\"font-size:14px;\">1. A multi-centre registry of RVHD</span></div>\n<div>\n <span style=\"font-size:14px;\">2. A prospective, randomized, parallel group, open-label clinical trial of rivaroxaban versus standard VKA therapy to evaluate non-inferiority of rivaroxaban to VKA, with testing for superiority if non-inferiority is satisfied.</span></div>\n<div>\n <span style=\"font-size:14px;\">3. A prospective, randomized, open-label superiority trial comparing rivaroxaban to aspirin in high risk patients either with AF and unsuitable for VKA or without AF and with high risk factors.</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:14px;\"><u><strong>Study Size</strong></u></span></div>\n<div>\n <span style=\"font-size:14px;\">RVHD Registry: 17,000 patients with RVHD (in addition to the existing registry which has already 3300 patients)</span></div>\n<div>\n <span style=\"font-size:14px;\">Non-Inferiority Trial of rivaroxaban versus VKAs: 4,500 patients</span></div>\n<div>\n <span style=\"font-size:14px;\">Superiority Trial of rivaroxaban versus aspirin: 2,000 patients</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:14px;\"><strong><u>Inclusion Criteria</u></strong></span></div>\n<div>\n <span style=\"font-size:14px;\">Registry: Any patient with RVHD diagnosed by echocardiography</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:14px;\"><strong>Non-Inferiority Trial:</strong></span></div>\n<div>\n <span style=\"font-size:14px;\">1. RVHD diagnosed by echocardiography at any time prior to enrollment</span></div>\n<div>\n <span style=\"font-size:14px;\">2. Age ≥18</span></div>\n<div>\n <span style=\"font-size:14px;\">3. Increased risk of stroke by any of the following</span></div>\n<div>\n <span style=\"font-size:14px;\">a) CHA2DS2-VASc score ≥ 2 OR</span></div>\n<div>\n <span style=\"font-size:14px;\">b) Moderate/Severe mitral stenosis with valve area ≤2.0 cm2 OR</span></div>\n<div>\n <span style=\"font-size:14px;\">c) Left atrial spontaneous echo contrast OR</span></div>\n<div>\n <span style=\"font-size:14px;\">d) Left atrial thrombus</span></div>\n<div>\n <span style=\"font-size:14px;\">4. Heart Rhythm</span></div>\n<div>\n <span style=\"font-size:14px;\">a) AF or Flutter should be documented on baseline 12-lead ECG, or on a previous 12-lead ECG, Holter monitor, in-hospital ECG rhythm strip or Pacemaker or ICD electrogram.</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:14px;\"><strong>Superiority Trial</strong></span></div>\n<div>\n <span style=\"font-size:14px;\">1. RVHD diagnosed by echocardiography at any time prior to enrollment</span></div>\n<div>\n <span style=\"font-size:14px;\">2. Age ≥18</span></div>\n<div>\n <span style=\"font-size:14px;\">3. Increased risk of stroke by any of the following</span></div>\n<div>\n <span style=\"font-size:14px;\">a) CHA2DS2-VASc score ≥ 2 OR</span></div>\n<div>\n <span style=\"font-size:14px;\">b) Moderate/Severe mitral stenosis with valve area ≤2.0 cm2 OR</span></div>\n<div>\n <span style=\"font-size:14px;\">c) Left atrial spontaneous echo contrast OR</span></div>\n<div>\n <span style=\"font-size:14px;\">d) Left atrial thrombus</span></div>\n<div>\n <span style=\"font-size:14px;\">4. Heart Rhythm</span></div>\n<div>\n <span style=\"font-size:14px;\">a) AF or Flutter and unsuitable for VKA therapy. (AF or Flutter should be documented on baseline 12-lead ECG, or on a previous 12-lead ECG, Holter monitor, in-hospital ECG rhythm strip or Pacemaker or ICD electrogram) OR</span></div>\n<div>\n <span style=\"font-size:14px;\">b) In the absence of AF or Flutter, patients would be eligible in the presence of any one of the following:</span></div>\n<div>\n <span style=\"font-size:14px;\">a. Left atrial enlargement ≥5.5 cm OR</span></div>\n<div>\n <span style=\"font-size:14px;\">b. Left atrial spontaneous echo contrast OR</span></div>\n<div>\n <span style=\"font-size:14px;\">c. Left atrial thrombus OR</span></div>\n<div>\n <span style=\"font-size:14px;\">d. Frequent ectopic atrial activity (>1000/24 hours) on Holter monitoring Exclusion Criteria</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:14px;\"><u><strong>Exclusion Criteria for both non-inferiority and superiority trials:</strong></u></span></div>\n<div>\n <span style=\"font-size:14px;\">1. Refusal to consent</span></div>\n<div>\n <span style=\"font-size:14px;\">2. Actively involved in any study that would compromise the protocol of INVICTUS Trial</span></div>\n<div>\n <span style=\"font-size:14px;\">3. Severe co-morbid condition with life expectancy < 1 year</span></div>\n<div>\n <div>\n <span style=\"font-size:14px;\">4. Other serious condition(s) or logistic factors likely to interfere with study participation or with the ability to complete the trial, as appropriate to country or region.</span></div>\n <div>\n <span style=\"font-size:14px;\">5. Likely to have valve replacement surgery within 6 months</span></div>\n <div>\n <span style=\"font-size:14px;\">6. Mechanical valve prosthesis or other condition requiring treatment with VKAs. Patients with deep vein thrombosis or recent pulmonary embolism can be enrolled where both VKAs and rivaroxaban are approved.</span></div>\n <div>\n <span style=\"font-size:14px;\">7. Contraindication to the study medication of the trial</span></div>\n <div>\n <span style=\"font-size:14px;\">a. Allergy to rivaroxaban</span></div>\n <div>\n <span style=\"font-size:14px;\">b. Allergy to VKAs ( non-inferiority trial)</span></div>\n <div>\n <span style=\"font-size:14px;\">c. Allergy to aspirin ( superiority trial)</span></div>\n <div>\n <span style=\"font-size:14px;\">8. Severe renal insufficiency with an calculated creatinine clearance (Cockcroft-Gault) < 15 ml/min</span></div>\n <div>\n <span style=\"font-size:14px;\">9. Serious bleeding in the past six months or at high risk for bleeding</span></div>\n <div>\n <span style=\"font-size:14px;\">10. Moderate to severe hepatic impairment</span></div>\n <div>\n <span style=\"font-size:14px;\">11. Ongoing need for dual antiplatelet therapy (patients with on-going aspirin therapy ≤100 mg per day are not excluded).</span></div>\n <div>\n <span style=\"font-size:14px;\">12. Ongoing need for dual strong inhibitors of CYP-3a4 or p-glycoprotein inhibitor.</span></div>\n <div>\n <span style=\"font-size:14px;\">13. Received an investigational drug in the past 30 days</span></div>\n <div>\n <span style=\"font-size:14px;\">14. Patients considered unsuitable for trial inclusion because of unwillingness to attend follow up visits</span></div>\n <div>\n <span style=\"font-size:14px;\">15. Women who are pregnant and/or breastfeeding</span></div>\n <div>\n <span style=\"font-size:14px;\">16. Women of child bearing age who do not use an effective form of birth control.</span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size:14px;\"><strong><u>Treatment Regimen</u></strong></span></div>\n <div>\n <span style=\"font-size:14px;\"><strong>Non-Inferiority Trial:</strong></span></div>\n <div>\n <span style=\"font-size:14px;\">Patients will be randomized either to receive rivaroxaban or any approved VKA. Treatment will be open-label.</span></div>\n <div>\n <span style=\"font-size:14px;\">1. Rivaroxaban Arm</span></div>\n <div>\n <span style=\"font-size:14px;\">- Rivaroxaban 20 mg once daily</span></div>\n <div>\n <span style=\"font-size:14px;\">- Rivaroxaban 15 mg once daily (for patients with an creatinine clearance ≥15 and <50 ml/min)</span></div>\n <div>\n <span style=\"font-size:14px;\">2. VKA Arm</span></div>\n <div>\n <span style=\"font-size:14px;\">- Any VKA approved for use in the participating country</span></div>\n <div>\n <span style=\"font-size:14px;\">- VKA titrated to achieve an INR of 2.0-3.0</span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size:14px;\"><strong>Superiority Trial:</strong></span></div>\n <div>\n <span style=\"font-size:14px;\">Patients will be randomized to receive rivaroxaban or aspirin. Treatment will be open-label.</span></div>\n <div>\n <span style=\"font-size:14px;\">1. Rivaroxaban Arm</span></div>\n <div>\n <span style=\"font-size:14px;\">- Rivaroxaban 15 mg once daily</span></div>\n <div>\n <span style=\"font-size:14px;\">- No dose reduction with renal impairment</span></div>\n <div>\n <span style=\"font-size:14px;\">2. Aspirin Arm</span></div>\n <div>\n <span style=\"font-size:14px;\">- Aspirin 75 to 100 mg once daily</span><br />\n <br />\n <div>\n <span style=\"font-size:14px;\"><strong>Registry Outcomes</strong></span></div>\n <div>\n <span style=\"font-size:14px;\">- All stroke by sub-type</span></div>\n <div>\n <span style=\"font-size:14px;\">- Systemic embolism</span></div>\n <div>\n <span style=\"font-size:14px;\">- Myocardial infarction</span></div>\n <div>\n <span style=\"font-size:14px;\">- Death by cause</span></div>\n <div>\n <span style=\"font-size:14px;\">- Recurrent rheumatic fever</span></div>\n <div>\n <span style=\"font-size:14px;\">- Prosthetic valve thrombosis</span></div>\n <div>\n <span style=\"font-size:14px;\">- Infective endocarditis</span></div>\n <div>\n <span style=\"font-size:14px;\">- Hospitalization for any cause.</span></div>\n <div>\n <span style=\"font-size:14px;\">- Valvuloplasty / Surgery</span></div>\n <div>\n <span style=\"font-size:14px;\">- Infections – Pneumonia, HIV etc. Clinical trial Efficacy Outcomes</span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size:14px;\"><strong>Primary Outcome:</strong></span></div>\n <div>\n <span style=\"font-size:14px;\">- Stroke(ischemic, hemorrhagic or undetermined type)</span></div>\n <div>\n <span style=\"font-size:14px;\">- Systemic embolism</span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size:14px;\"><strong>Secondary Outcomes</strong>:</span></div>\n <div>\n <span style=\"font-size:14px;\">- Myocardial infarction</span></div>\n <div>\n <span style=\"font-size:14px;\">- Hospitalization</span></div>\n <div>\n <span style=\"font-size:14px;\">- Vascular death</span></div>\n <div>\n <span style=\"font-size:14px;\">- Total Death</span></div>\n <div>\n <span style=\"font-size:14px;\">- Composite of stroke, myocardial infarction, systemic embolism, vascular death</span></div>\n <div>\n  </div>\n <div>\n <div>\n <span style=\"font-size:14px;\"><u><strong>Statistical Considerations</strong></u></span></div>\n <div>\n <span style=\"font-size:14px;\"><em><strong>Registry</strong></em>: A sample size of 20,000 (combined REMEDY (3000) and INVICTUS (17,000)) will ensure precise measurement of event rates as infrequent as 0.5/per 100 patient-years, with an absolute precision of 0.1% and 95% confidence.</span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size:14px;\"><em><strong>Non-Inferiority Trial: </strong></em>The sample-size calculations are based on a non-inferiority margin of 1.46 and an expected primary annual event rate of 2% per year in the VKA arm. Study enrolment will occur over two years and all patients will be followed to a common termination at the end of an additional 2 years of follow up or for a total of about four years. Thus, the mean follow-up time will be approximately three years. Assuming 10% non-compliance to rivaroxaban in the first year with additional non-compliance of 5% per year thereafter, enrolment of 4,500 patients will give 86% power to conclude that rivaroxaban is non-inferior to VKAs or the primary outcome. If non-inferiority is established, then testing for superiority of rivaroxaban over VKA will be undertaken without statistical penalty.</span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size:14px;\"><em><strong>Superiority Trial: </strong></em>The sample-size calculations are based on an expected primary annual event rate on aspirin of 3.5%. Study enrolment will occur over two years and all patients will be followed to a common termination at the end of four years. Thus, the mean follow-up time will be approximately three years. We expect a relative risk reduction of 45% Assuming 10% non-compliance to rivaroxaban in the first year with additional non-compliance of 5% per year thereafter, enrolment of 2,000 patients will give 95% power to conclude that rivaroxaban is superior to asprin.</span></div>\n </div>\n </div>\n</div>\n<div>\n  </div>\n<p style=\"text-align: justify;\">\n  </p>\n<p style=\"text-align: justify;\">\n <br />\n  </p>\n
      • study_title<p>\n INVESTIGATION OF RHEUMATIC AF TREATMENT USING VITAMIN K ANTAGONISTS, RIVAROXABAN OR ASPRIN STUDIES</p>\n
      • laymans_summary<p>\n INVICTUS study is an international multicenter trial investigating the safety and efficacy of rivaroxaban in prevention of stroke in patients with rheumatic valvular heart disease. Rheumatic valvular heart disease is a condition in which the way through which blood passes into the heart is either narrow or leaks. This normally weakens the heart muscles and can cause abnormal heartbeats known as atrial fibrillation (AF).  Atrial fibrillation (AF) can cause blood clots in the heart, which travel to the brain. When blood clot in the heart goes to the brain, it is called stroke, symptoms may be weakness in an arm or leg, or loss of feeling or loss of ability to speak or even death. Drugs to prevent blood coagulation are used to reduce stroke in patients with atrial fibrillation. In rheumatic valvular heart disease, drugs used to prevent blood clots are called vitamin k antagonist, including warfarin or acenocoumarol or phenprocoumon. These antagonists of Vitamin K are effective in reducing stroke but difficult to use because they require regular monitoring. Recently, new drugs to prevent blood clots that are easy to use have shown to be effective in patients with atrial fibrillation but do not have rheumatic valvular heart disease. However, these new drugs have not been tested in patients with rheumatic valvular heart disease and therefore, their use in these patients has not been approved. The purpose of the Invictus study is to test if one of these new drugs, called rivaroxaban is good as a vitamin k antagonist drug for preventing stroke in patients with abnormal heartbeats (AF) and Rheumatic valvular heart disease.</p>\n<p>\n  </p>\n
      • short_titleINVICTUS
      • protocol_noECCT/16/10/01
      • version_no3.0 - 2015 -10 -19
      • date_of_protocol19-10-2015
      • study_drugRivaroxaban
      • disease_conditionRheumatic Atrial Fibrillation
      • 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_nameNew Oral Anticoagulants
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameWarfarin
      • comparator_registeredYES
      • comparator_countriesArgentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Denmark, Finland, France, Great Britain, Greece, Germany, India, Israel, Italy, Kenya, Korea, Malaysia, Mexico, Netherlands, Norway, New Zealand Peru, Philippines, Russia, Spain, South Africa, Sweden, Switzerland Taiwan, Tanzania,Thailand, Turkey and Venezuela,Uganda, Ukraine, United States.
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressgituramurenga@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_countries1
      • 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_plan0
      • applicant_contractual_agreement0
      • declaration_applicantDr. Bernard Muriuki Gitura
      • declaration_date103-10-2016
      • declaration_principal_investigatorDR. BERNARD MURIUKI GITURA
      • declaration_date203-10-2016
      • placebo_presentNo
      • study_objectives<div>\n 1 In patients with rheumatic valvular heart disease (RVHD) and who are in atrial fibrillation or flutter (AF/Flutter) and have other stroke risk factors, rivaroxaban is non-inferior to vitamin K antagonists (VKA) for prevention of stroke or systemic embolism. </div>\n<div>\n 2 In patients with RVHD either with AF/Flutter but unsuitable for VKA therapy or with sinus rhythm but with high risk, rivaroxaban is superior to aspirin for prevention of stroke or systemic embolism. </div>\n
      • principal_inclusion_criteria<div>\n <span style=\"font-size:16px;\"><u><strong>Registry:</strong></u> Any patient with RVHD diagnosed by echocardiography</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:16px;\"><u><strong>Non-Inferiority Trial:</strong></u></span></div>\n<div>\n <span style=\"font-size:16px;\">1. RVHD diagnosed by echocardiography at any time prior to enrollment</span></div>\n<div>\n <span style=\"font-size:16px;\">2. Age ≥18</span></div>\n<div>\n <span style=\"font-size:16px;\">3. Increased risk of stroke by any of the following</span></div>\n<div>\n <span style=\"font-size:16px;\">a) CHA2DS2-VASc score ≥ 2 OR</span></div>\n<div>\n <span style=\"font-size:16px;\">b) Moderate/Severe mitral stenosis with valve area ≤2.0 cm2 OR</span></div>\n<div>\n <span style=\"font-size:16px;\">c) Left atrial spontaneous echo contrast OR</span></div>\n<div>\n <span style=\"font-size:16px;\">d) Left atrial thrombus</span></div>\n<div>\n <span style=\"font-size:16px;\">4. Heart Rhythm</span></div>\n<div>\n <span style=\"font-size:16px;\">a) AF or Flutter should be documented on baseline 12-lead ECG, or on a</span></div>\n<div>\n <span style=\"font-size:16px;\">previous 12-lead ECG, Holter monitor, in-hospital ECG rhythm strip or</span></div>\n<div>\n <span style=\"font-size:16px;\">Pacemaker or ICD electrogram.</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:16px;\"><strong><u>Superiority trial</u></strong></span><br />\n <br />\n <div>\n <span style=\"font-size:16px;\">1. RVHD diagnosed by echocardiography at any time prior to enrollment</span></div>\n <div>\n <span style=\"font-size:16px;\">2. Age ≥18</span></div>\n <div>\n <span style=\"font-size:16px;\">3. Increased risk of stroke by any of the following</span></div>\n <div>\n <span style=\"font-size:16px;\">a) CHA2DS2-VASc score ≥ 2 OR</span></div>\n <div>\n <span style=\"font-size:16px;\">b) Moderate/Severe mitral stenosis with valve area ≤2.0 cm2 OR</span></div>\n <div>\n <span style=\"font-size:16px;\">c) Left atrial spontaneous echo contrast OR</span></div>\n <div>\n <span style=\"font-size:16px;\">d) Left atrial thrombus</span></div>\n <div>\n <span style=\"font-size:16px;\">4. Heart Rhythm</span></div>\n <div>\n <span style=\"font-size:16px;\">a) AF or Flutter and unsuitable for VKA therapy. (AF or Flutter should be</span></div>\n <div>\n <span style=\"font-size:16px;\">documented on baseline 12-lead ECG, or on a previous 12-lead ECG,</span></div>\n <div>\n <span style=\"font-size:16px;\">Holter monitor, in-hospital ECG rhythm strip or Pacemaker or ICD</span></div>\n <div>\n <span style=\"font-size:16px;\">electrogram) OR</span></div>\n <div>\n <span style=\"font-size:16px;\">b) In the absence of AF or Flutter, patients would be eligible in the presence</span></div>\n <div>\n <span style=\"font-size:16px;\">of any one of the following:</span></div>\n <div>\n <span style=\"font-size:16px;\">a. Left atrial enlargement ≥5.5 cm OR</span></div>\n <div>\n <span style=\"font-size:16px;\">b. Left atrial spontaneous echo contrast OR</span></div>\n <div>\n <span style=\"font-size:16px;\">c. Left atrial thrombus OR</span></div>\n <div>\n <span style=\"font-size:16px;\">d. Frequent ectopic atrial activity (>1000/24 hours) on Holter monitoring</span></div>\n</div>\n<p>\n  </p>\n
      • principal_exclusion_criteria<p>\n <span style=\"font-size:16px;\"><u><strong>Exclusion Criteria for both non-inferiority and superiority trials:</strong></u></span></p>\n<div>\n <span style=\"font-size:16px;\">1. Refusal to consent</span></div>\n<div>\n <span style=\"font-size:16px;\">2. Actively involved in any study that would compromise the protocol of</span></div>\n<div>\n <span style=\"font-size:16px;\">INVICTUS Trial</span></div>\n<div>\n <span style=\"font-size:16px;\">3. Severe co-morbid condition with life expectancy < 1 year</span></div>\n<div>\n <span style=\"font-size:16px;\">4. Other serious condition(s) or logistic factors likely to interfere with study</span></div>\n<div>\n <span style=\"font-size:16px;\">participation or with the ability to complete the trial, as appropriate to country</span></div>\n<div>\n <span style=\"font-size:16px;\">or region.</span></div>\n<div>\n <span style=\"font-size:16px;\">5. Likely to have valve replacement surgery within 6 months</span></div>\n<div>\n <span style=\"font-size:16px;\">6. Mechanical valve prosthesis or other condition requiring treatment with VKAs.</span></div>\n<div>\n <span style=\"font-size:16px;\">Patients with deep vein thrombosis or recent pulmonary embolism can be</span></div>\n<div>\n <span style=\"font-size:16px;\">enrolled where both VKAs and rivaroxaban are approved.</span></div>\n<div>\n <span style=\"font-size:16px;\">7. Contraindication to the study medication of the trial</span></div>\n<div>\n <span style=\"font-size:16px;\">a. Allergy to rivaroxaban</span></div>\n<div>\n <span style=\"font-size:16px;\">b. Allergy to VKAs ( non-inferiority trial)</span></div>\n<div>\n <span style=\"font-size:16px;\">c. Allergy to aspirin ( superiority trial)</span></div>\n<div>\n <span style=\"font-size:16px;\">8. Severe renal insufficiency with an calculated creatinine clearance (Cockcroft-</span></div>\n<div>\n <span style=\"font-size:16px;\">Gault) < 15 ml/min</span></div>\n<div>\n <span style=\"font-size:16px;\">9. Serious bleeding in the past six months or at high risk for bleeding</span></div>\n<div>\n <span style=\"font-size:16px;\">10. Moderate to severe hepatic impairment</span></div>\n<div>\n <span style=\"font-size:16px;\">11. Ongoing need for dual antiplatelet therapy (patients with on-going aspirin</span></div>\n<div>\n <span style=\"font-size:16px;\">therapy ≤100 mg per day are not excluded).</span></div>\n<div>\n <span style=\"font-size:16px;\">12. Ongoing need for dual strong inhibitors of CYP-3a4 or p-glycoprotein</span></div>\n<div>\n <span style=\"font-size:16px;\">inhibitor.</span></div>\n<div>\n <span style=\"font-size:16px;\">13. Received an investigational drug in the past 30 days</span></div>\n<div>\n <span style=\"font-size:16px;\">14. Patients considered unsuitable for trial inclusion because of unwillingness to</span></div>\n<div>\n <span style=\"font-size:16px;\">attend follow up visits</span></div>\n<div>\n <span style=\"font-size:16px;\">15. Women who are pregnant and/or breastfeeding</span></div>\n<div>\n <span style=\"font-size:16px;\">16. Women of child bearing age who do not use an effective form of birth control.</span></div>\n<div>\n  </div>\n
      • primary_end_points<div>\n <span style=\"font-size:12px;\"><u><strong>Clinical Trial Efficacy Outcomes</strong></u></span></div>\n<div>\n <span style=\"font-size:12px;\"> Assessments and procedures at occurrence of efficacy outcome events</span></div>\n<div>\n <span style=\"font-size:12px;\">Occurrence of outcomes must be reported within 3 days of the site’s notification of the</span></div>\n<div>\n <span style=\"font-size:12px;\">event. Patients are requested to inform the site as soon as possible if they are hospitalized</span></div>\n<div>\n <span style=\"font-size:12px;\">(regardless of reason) in order to ensure timely identification of potential CV events.</span></div>\n<div>\n <span style=\"font-size:12px;\">The following events will be reported on Outcome/CV Event reporting forms and</span></div>\n<div>\n <span style=\"font-size:12px;\">will undergo blinded adjudication by expert adjudicators.</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Stroke</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Systemic embolism</span></div>\n<div>\n <span style=\"font-size:12px;\">In addition to investigator identified CV events, safety data will be reviewed regularly for</span></div>\n<div>\n <span style=\"font-size:12px;\">potential CV events. In particular, Medical Dictionary for Regulatory Activities</span></div>\n<div>\n <span style=\"font-size:12px;\">(MedDRA) preferred terms assigned to investigator reported AEs will be screened for</span></div>\n<div>\n <span style=\"font-size:12px;\">potential outcome events and investigators may then be asked to further investigate</span></div>\n<div>\n <span style=\"font-size:12px;\">whether or not a CV event occurred and potentially initiate the outcomes reporting process.</span></div>\n<div>\n <span style=\"font-size:12px;\"><strong>Definition of efficacy outcome events (Primary and Secondary)</strong></span></div>\n<div>\n <span style=\"font-size:12px;\">The following Primary efficacy outcome events will be assessed and are defined in the</span></div>\n<div>\n <span style=\"font-size:12px;\">Stroke is defined as any focal neurologic deficit lasting>24 hours with or without brain</span></div>\n<div>\n <span style=\"font-size:12px;\">imaging suggestive of a primary ischemic origin leading to tissue infarction. Neuroimaging</span></div>\n<div>\n <span style=\"font-size:12px;\">evidence should be provided wherever possible. Transient ischemic attack with positive neuroimaging</span></div>\n<div>\n <span style=\"font-size:12px;\">will be considered a stroke</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:12px;\"><strong> Systemic embolism</strong></span></div>\n<div>\n <span style=\"font-size:12px;\">Systemic embolism is defined as abrupt vascular insufficiency associated with clinical or</span></div>\n<div>\n <span style=\"font-size:12px;\">radiological evidence of arterial occlusion in the absence of other likely mechanisms.</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:12px;\"><strong>Myocardial infarction</strong></span></div>\n<div>\n <span style=\"font-size:12px;\">The term acute MI is used when there is evidence of myocardial necrosis in a clinical setting</span></div>\n<div>\n <span style=\"font-size:12px;\">consistent with acute myocardial ischemia. The diagnosis of MI requires the combination of:</span></div>\n<div>\n <span style=\"font-size:12px;\">• Evidence of myocardial necrosis (either changes in cardiac biomarkers or post-mortem</span></div>\n<div>\n <span style=\"font-size:12px;\">pathological findings); and</span></div>\n<div>\n <span style=\"font-size:12px;\">• Supporting information derived from the clinical presentation, electrocardiographic</span></div>\n<div>\n <span style=\"font-size:12px;\">changes, or the results of myocardial or coronary artery imaging</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:12px;\"><strong> Vascular death</strong></span></div>\n<div>\n <span style=\"font-size:12px;\">Vascular death includes death due to stroke, myocardial infarction, heart failure or cardiogenic</span></div>\n<div>\n <span style=\"font-size:12px;\">shock, sudden death or any other death due to other cardiovascular causes. In addition, death</span></div>\n<div>\n <span style=\"font-size:12px;\">due to hemorrhage will be included.</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:12px;\"><u><strong>Clinical Safety Outcomes</strong></u></span></div>\n<div>\n <span style=\"font-size:12px;\">The safety outcomes are bleeding events using the International Society on Thrombosis and</span></div>\n<div>\n <span style=\"font-size:12px;\">Haemostasis (ISTH) major bleeding definition, and other definitions derived from these as listed in</span></div>\n<div>\n <span style=\"font-size:12px;\">Section 6.9.1 and Section 6.9.2. Bleeding events will be reported on the bleeding reporting forms</span></div>\n<div>\n <span style=\"font-size:12px;\">and exempted from SAE reporting.</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:12px;\"><em><strong>6.9.1 Primary safety variable</strong></em></span></div>\n<div>\n <span style=\"font-size:12px;\">The primary safety variable is the time from randomization to time of first occurrence of a</span></div>\n<div>\n <span style=\"font-size:12px;\">major bleeding defined as a bleeding event that meets at least one of the following criteria:</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Fatal bleeding, and/or</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Bleeding in a critical area or organ (intracranial, intraocular, intraspinal, pericardial,</span></div>\n<div>\n <span style=\"font-size:12px;\">retroperitoneal, intraarticular, or intramuscular with compartment syndrome), and/or</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Clinically overt bleeding associated with a recent decrease in the haemoglobin level of</span></div>\n<div>\n <span style=\"font-size:12px;\">more than 2 g/dL (20 g/L; 1.24 mmol/L) compared to the most recent haemoglobin</span></div>\n<div>\n <span style=\"font-size:12px;\">value available before the event, and/or</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Clinically overt bleeding leading to transfusion of 2 or more units of packed red blood</span></div>\n<div>\n <span style=\"font-size:12px;\">cells or whole blood</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:12px;\"><em><strong>6.9.2 Secondary safety variable</strong></em></span></div>\n<div>\n <span style=\"font-size:12px;\">The secondary safety variables are the time from randomization to time of first occurrence of:</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Life-threatening bleeding, defined as a subset of major bleeding that meet at least one</span></div>\n<div>\n <span style=\"font-size:12px;\">of the following criteria:</span></div>\n<div>\n <span style=\"font-size:12px;\">o Fatal bleeding</span></div>\n<div>\n <span style=\"font-size:12px;\">o Symptomatic intracranial bleeding</span></div>\n<div>\n <span style=\"font-size:12px;\">o Reduction in haemoglobin of at least 5 g/dl (50 g/l; 3.10 mmol/L)</span></div>\n<div>\n <span style=\"font-size:12px;\">o Transfusion of at least 4 units of packed red cells or whole blood</span></div>\n<div>\n <span style=\"font-size:12px;\">o Associated with hypotension requiring the use of intravenous inotropic agents</span></div>\n<div>\n <span style=\"font-size:12px;\">o Necessitated surgical intervention</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Clinically relevant non-major bleeding, defined as non-major overt bleeding but</span></div>\n<div>\n <span style=\"font-size:12px;\">o Requires medical attention (e.g., hospitalization, medical treatment for</span></div>\n<div>\n <span style=\"font-size:12px;\">bleeding), and/orfollowing subsections of this protocol:</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Stroke </span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Systemic embolism </span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:12px;\">The following Secondary efficacy outcome events will be assessed and are defined in the</span></div>\n<div>\n <span style=\"font-size:12px;\">following subsections of this protocol:</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· MI </span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Vascular death </span></div>\n<div>\n <span style=\"font-size:12px;\">Additional detailed definitions for these efficacy outcomes will be provided in a separate</span></div>\n<div>\n <span style=\"font-size:12px;\">Adjudication manual.</span></div>\n<div>\n <span style=\"font-size:12px;\"> Stroke</span></div>\n<div>\n <span style=\"font-size:12px;\">o Is associated with a study drug interruption of more than 14 days.</span></div>\n<div>\n  </div>\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_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n KENYATTA NATIONAL HOSPITAL<br />\n Professor Elijah Nyainda Ogola, MbChB, Mmed, FACC - site principal investigator<br />\n Dr. Bernard Muriuki Gitura, MbChB, Mmed, Cert C - co-principal investigator<br />\n Peninah Kinuthia- Research Coordinator<br />\n <br />\n MOI TEACHING AND REFERRAL HOSPITAL<br />\n Dr. Felix Ayub Barasa- Site Principal Investigator<br />\n Dr. Benson Njuguna- Trial Pharmacist<br />\n Samuel Anaynje- pharmaceutical Technologist<br />\n Caudencia Chepkorir-  Trial Research Nurse<br />\n <br />\n THE KAREN HOSPITAL<br />\n Dr. Anthony Gikonyo- Site Principal Investigator<br />\n Dr. Stephen Omondi- coprincipal Investigator<br />\n Dr. Christina Mulwa- Trial pharmacist<br />\n Betty Weru Trial research nurse<br />\n Fredah Mwangi Study Coordinator<br />\n Duncan Luvayo Study Coordinator</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  </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  </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  </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  </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  </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  </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 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 </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  </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  </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  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n <br />\n <br />\n  </p>\n
      • other_details_explanation<p>\n Vitamin K Antagonists (VKAs) for example Warfarin are the main drugs administered for prevention of thrombo- embolic events in patients with Rheumatic Valve Heart Disease (RVHD) with Atrila Fibrillation (AF). The limiting factor with VKAs is that they need frequent monitoring to ensure safety and  efficacy of the drug. This can be particularly difficult in developing countries. The trial hopes to establish rivaroxaban as a safe and effective alternative treatment for valvular atrial fibrillation with need for minimal monitoring.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n 1. KNH/UON ERC 28th June 2016</p>\n<p>\n 2 MOI Teaching and Referral Hospital IREC</p>\n
      • other_details_regulatory_rejected<p>\n NONE</p>\n
      • other_details_regulatory_halted<p>\n NOT APPLICABLE</p>\n
      • estimated_duration5 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_comparatorVitamin K antagonist
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states29
      • number_of_sites3
      • multi_country_listAngola, Botswana, Brazil, Cameroon, Ethiopia, India, Indonesia, Kazakhstan, Kenya, Kyrgyzstan, Mexico, Mozambique, Namibia, Nigeria, Pakistan, Paraguay, Philippines, Rwanda, South Africa, Sudan, Tanzania, Uganda, Zambia, Zimbabwe
      • data_monitoring_committeeYes
      • total_enrolment_per_siteKenyatta National Hospital 5 participants per month\nThe Karen Hospital 3 participants per month\nMoi Teaching and Referral Hospital 7 participants per month\n
      • total_participants_worldwide4500
      • 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_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_nameBernard
      • investigator1_middle_nameMuriuki
      • investigator1_family_nameGitura
      • investigator1_qualificationMbChB,Mmed,Cert C
      • investigator1_professional_addressHospital Road, Box 2249 00202 KNH
      • investigator1_telephone+254717977637
      • investigator1_emailbgit27@gmail.com
      • organisations_transferred_Yes
      • number_participants250
      • notification<p>\n NOT APPLICABLE</p>\n
      • approval_date07-03-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted24-09-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n BACKGROUND Testing of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease–associated atrial fibrillation has been limited.</p>\n<p>\n METHODS We enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHA2 DS2 VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating a higher risk of stroke), a mitral-valve area of no more than 2 cm2 , left atrial spontaneous echo contrast, or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K antagonist. The primary efficacy outcome was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. We hypothesized that rivaroxaban therapy would be noninferior to vitamin K antagonist therapy. The primary safety outcome was major bleeding according to the International Society of Thrombosis and Hemostasis.</p>\n<p>\n RESULTS Of 4565 enrolled patients, 4531 were included in the final analysis. The mean age of the patients was 50.5 years, and 72.3% were women. Permanent discontinuation of trial medication was more common with rivaroxaban than with vitamin K antagonist therapy at all visits. In the intention-to-treat analysis, 560 patients in the rivaroxaban group and 446 in the vitamin K antagonist group had a primary-outcome event. Survival curves were nonproportional. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the vitamin K antagonist group (difference, −76 days; 95% confidence interval [CI], −121 to −31; P<0.001). A higher incidence of death occurred in the rivaroxaban group than in the vitamin K antagonist group (restricted mean survival time, 1608 days vs. 1680 days; difference, −72 days; 95% CI, −117 to −28). No significant between-group difference in the rate of major bleeding was noted.</p>\n<p>\n CONCLUSIONS Among patients with rheumatic heart disease–associated atrial fibrillation, vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; INVICTUS ClinicalTrials.gov number, NCT02832544.</p>\n
      • implication_results<p>\n In patients with atrial fibrillation not related to rheumatic heart disease, treatment with rivaroxaban or other factor Xa inhibitors has been shown to be noninferior to warfarin therapy for stroke prevention, with large reduction in the risk of hemorrhagic stroke.</p>\n<p>\n No evidence suggests that rivaroxaban therapy increases mortality among patients with other heart conditions. Treatment with rivaroxaban reduces mortality substantially among patients with atherosclerotic vascular disease. Thus, our data support the hypothesis that vitamin K antagonist therapy reduces the risk of death from vascular causes among patients with rheumatic heart disease; this effect appears to be independent of the prevention of atrial fibrillation–related stroke and suggests a direct effect on the disease process of rheumatic heart disease. Our trial showed that as compared with rivaroxaban, vitamin K antagonist therapy led to a lower rate of ischemic stroke among patients with rheumatic heart disease–associated atrial fibrillation and lower mortality due to vascular causes, without significantly increasing the rate of major bleeding. The results of this trial support current guidelines, which recommend vitamin K antagonist therapy for the prevention of stroke in patients with rheumatic heart disease in whom atrial fibrillation develops</p>\n<p>\n  </p>\n
      • quantity_imported
      • quantity_dispensed
      • quantity_destroyed
      • quantity_exported
      • balance_site
      • final_date0000-00-00
      • modified2023-02-19 18:46:08
      • created2016-09-04 19:24:59
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id355
        • application_id552
        • given_nameElijah
        • middle_nameNyainda
        • family_nameOgola
        • qualificationMbChB,Mmed, FACC
        • professional_addressP.O. BOX 19676- 00202 NAIROBI
        • telephone+254 (0) 723174268
        • emailelijah.ogola@uonbi.ac.ke
        • created2016-09-04 19:46:40
        • modified2020-09-24 09:01:22
      • 1(array)
        • id363
        • application_id552
        • given_namefelix
        • middle_nameayub
        • family_namebarasa
        • qualificationMbChB, Mmed
        • professional_addressP.O. BOX 8584-30100 ELDORET
        • telephone+254 723 174 268
        • emailbarasaceo12@gmail.com
        • created2016-10-03 11:28:35
        • modified2020-09-24 09:01:22
    • SiteDetail(array)
      • 0(array)
        • id422
        • application_id552
        • county_id47
        • site_nameKenyatta National hospital
        • physical_addressHospital Road
        • contact_detailsBox 20723 00202, Tel 726300
        • contact_personDr Bernard Gitura
        • site_capacity(null)
        • misc(null)
        • created2016-09-04 19:46:40
        • modified2020-09-24 09:01:22
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id423
        • application_id552
        • county_id27
        • site_nameMoi teaching and Referral Hospital
        • physical_addressNandi Road, Eldoret
        • contact_detailsP.O. Box 3-30100 Eldoret, +254 (053)2061749
        • contact_personDr Felix Ayub Barasa
        • site_capacity(null)
        • misc(null)
        • created2016-09-04 21:46:07
        • modified2020-09-24 09:01:22
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
      • 2(array)
        • id425
        • application_id552
        • county_id47
        • site_nameThe Karen Hospital
        • physical_addressLangata Road - Karen
        • contact_detailsP.O. Box 74240- 00200 Nairobi, +254 (0)20 661300
        • contact_personDr Anthony Gikonyo
        • site_capacity(null)
        • misc(null)
        • created2016-09-04 21:46:07
        • modified2020-09-24 09:01:22
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id283
        • application_id552
        • sponsorHamilnton Health sciences, hamilnton,ON, Canada
        • sponsor_typeResearch Institution
        • contact_person
        • address237 Barton Street East, Hamilton,Ontario, Canada L8L 2X2
        • telephone_number905 527 4322 ext 40596
        • fax_number
        • cell_number905 527 4322 ext 40596
        • email_addressinvictus@phri.ca
        • created2016-09-04 19:46:40
        • modified2020-09-24 09:01:22
  • 2(array)
    • Application(array)
      • id539
      • user_id613
      • trial_status_id5
      • abstract_of_study<p style=\"margin-left:5.05pt;\">\n Tuberculosis (TB) is one of the most important global health problems. Kenya is ranked 15th among the 22 high TB burden countries that account for 80% of the global TB burden. An estimated two billion persons carry latent Mycobacterium tuberculosis (MTB). Treatment of latent tuberculosis infection (LTBI) is critical to global tuberculosis control and elimination. Pregnant women are at increased risk of progressing from latent LTBI to active tuberculosis because pregnancy suppresses the immune response. Symptoms of active TB may not be seen until after delivery, when the immune suppression reverses and symptoms are exacerbated. The World Health Organization (WHO) currently recommends treating LTBI with daily isoniazid (INH) for all HIV- infected pregnant women, but few programs have implemented this policy. Adherence and toxicity concerns remain the main barriers to treatment. Pregnancy and infant outcomes of women taking isoniazid for active TB treatment are comparable to normal pregnant women not receiving TB treatment, but toxicity concerns persist due to the suboptimal quality of existing studies. The US Centers for Disease Control and Prevention (CDC) recommends the use of either nine months of daily isoniazid monotherapy or a newer regimen of three months of weekly isoniazid and rifapentine (RPT) which is recommended in otherwise healthy patients over the age of 12 years who have LTBI. Though the CDC states that the regimen can be considered in other populations when it offers “practical advantages,” the regimen is not recommended in pregnant women, because the safety of the regimen in pregnancy is unknown. This study aims to address this gap in knowledge. This study aims to evaluate the pharmacokinetics, safety and tolerability of RPT and INH dosed once weekly for 12 doses in HIV-1 infected and HIV-1 uninfected pregnant women with latent TB infection at high risk for development of TB. The study will also describe the safety infant outcomes among infants born to women receiving once weekly RPT/INH. HIV-1 infected and HIV-1 uninfected pregnant women with latent TB and their infants will be enrolled into two cohorts based on gestation and started on RPT and INH once weekly for 12 weeks. Women in Cohort 1 will be enrolled in the second trimester of pregnancy (≥14 to <28 weeks); women in Cohort 2 will be enrolled in the third trimester of pregnancy (≥28 to ≤34 weeks). The Kericho site will recruit up to 20 participants and after completing the study drug regimen, participants will be followed until 24 weeks postpartum. This study is to inform practice on appropriate use of this regimen in pregnant and postpartum women that achieves concentrations similar to non-pregnant adults, in whom efficacy has been established. It is anticipated that this study will generate useful PK data to help inform next steps for an amendment to this protocol or a separate future study.</p>\n
      • study_title<p style=\"margin-left:2.85pt;\">\n <span style=\"font-size:12px;\">A Phase I/II Trial of the Pharmacokinetics, Tolerability, and Safety of Once-Weekly Rifapentine and Isoniazid in HIV-1-infected and HIV-1-uninfected Pregnant and Postpartum Women with Latent Tuberculosis Infection</span></p>\n
      • laymans_summary<p>\n This study is being done because TB is a major cause of illness and death in women of reproductive age. In countries where TB is common, up to half of all women are infected with TB. There are two types of TB that may occur when exposed to TB. In one type, people may become sick with symptoms such as cough and fever and these people are also contagious, meaning they can pass TB to other people. This type of TB is known as active TB disease. In the other type, people do not become sick or contagious, but they still have TB in an inactive form. This inactive form is known as latent TB. If latent TB is not treated, it can become active TB, and this often happens for women around the time of pregnancy. Maternal TB can be passed on to the babies causing illness or death. There are medicines that help prevent latent TB from becoming active TB. These medicines, Rifapentine and Isoniazid are widely used by people who are not pregnant. The purpose of this study is to test how these medicines are taken up in the body also called pharmacokinetic tests (PK), how they are tolerated and the safety of the medicines for pregnant women and their babies.</p>\n<p>\n  </p>\n<p>\n This is a multi-center study that will enroll HIV-1-infected and HIV-1- uninfected pregnant women with latent TB infection and their infants. Women will be enrolled into two cohorts based on gestation and started on RPT and INH once weekly for 12 weeks (at Entry and 11 weekly follow-up visits). Women in Cohort 1 will be enrolled at a pregnancy gestation between 14 and < 28 weeks; women in Cohort 2 will be enrolled at a pregnancy gestation between 28 to 34 weeks. In total across all study sites, up to 82 pregnant women will be enrolled to yield 50 evaluable women (a minimum of 25 evaluable women in each cohort) and their infants. Women are considered evaluable if they contribute any data to the PK sampling collections or complete the study drug regimen. The Kericho site will recruit up to 20 participants and after completing the study drug regimen, participants will be followed until 24 weeks postpartum then they are transitioned to the primary health care providers. The study will benefit the society by informing practice on appropriate use of these medicines in pregnant and postpartum women for prevention of active TB disease. It is anticipated that this study will generate useful data to help inform next steps for an amendment to this protocol or a separate future study.</p>\n<p>\n Participants will be informed of all potential risks from the treatment that they will receive which involve the side effects of medicine to be given. Taking blood may cause some discomfort, bleeding, or bruising where the needle enters the body, and in rare cases, fainting or infection. Taking TB preventative medicine, as well as vitamin B6, may provide a benefit to the mother and her infant. Furthermore, early detection of TB may be a benefit and would help prevent transmission of TB to the infant. Participants will receive clinical examination, laboratory testing, and TB signs and symptoms counseling. For other medical conditions identified as part of the study screening and/or follow-up procedures, participants will be managed at KEMRI WRP CRC or referred to other sources of care available in the community</p>\n
      • short_titleIMPAACT 2001
      • protocol_noECCT/16/08/03
      • version_noVersion 1.0
      • date_of_protocol10-11-2015
      • study_drugRifapentine and Isoniazid
      • disease_conditionLatent 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_nameRifapentine and Isoniazid
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressdeborah.langat@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_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data0
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • 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_applicantKEMRI WRP Kericho P.O Box 1357-20200, Kericho
      • declaration_date125-08-2016
      • declaration_principal_investigatorDeborah C. Langat
      • declaration_date225-08-2016
      • placebo_presentNo
      • study_objectives<h2>\n <span style=\"font-size: 12px;\">Primary Objective</span></h2>\n<ol>\n <li>\n To estimate the population pharmacokinetics (PK) (CL/F, absorption, volume of distribution) of RPT and its desacetyl-rifapentine metabolite (desRPT) among pregnant women during the second trimester and third trimester who are receiving once-weekly RPT (900mg or the new study dose, if a dose adjustment is indicated by the interim analysis) and once-weekly INH (900mg).</li>\n <li>\n To estimate the incidence of serious adverse events (SAEs) related to RPT + INH dosed once weekly for 12 weeks (at entry and 11 weekly follow-up visits) in pregnant women.</li>\n <li>\n To describe the infant safety outcomes among infants born to women receiving once-weekly RPT + INH.</li>\n</ol>\n<p>\n Secondary Objectives</p>\n<ol>\n <li>\n To estimate the population pharmacokinetics (PK) (CL/F, absorption, volume of distribution) of RPT and its desacetyl-rifapentine metabolite (desRPT) among pregnant women during the postpartum period who are receiving once-weekly RPT (900mg or the new study dose, if a dose adjustment is indicated by the interim analysis) and once-weekly INH (900mg).</li>\n <li>\n To assess the impact of covariates (gestational age, weight, age, HIV status) on primary PK</li>\n <li>\n To compare RPT and desRPT exposure pharmacokinetic parameters (AUC, Cmax, Cmin) for RPT in pregnant and postpartum women versus non-pregnant historical controls, using non-compartmental analyses</li>\n <li>\n To determine the RPT dose in pregnancy that achieves similar estimated exposure (AUC) of RPT</li>\n <li>\n To quantify RPT and desRPT concentrations at delivery among infants born to women receiving once-weekly RPT + INH</li>\n <li>\n To describe the tolerability of RPT + INH dosed once weekly for 12 weeks (at entry and 11 weekly follow-up visits) in pregnant and postpartum women</li>\n <li>\n To assess incidence of active TB in mother-infant pairs up to 24 weeks postpartum</li>\n <li>\n To explore the population pharmacokinetics (PK) (CL/F, absorption, volume of distribution) of INH in HIV-1-infected and HIV-1-uninfected pregnant and postpartum women (i.e., women who are and are not taking efavirenz (EFV)) who are receiving once-weekly RPT (900mg or the new study dose, if a dose adjustment is indicated by the interim analysis) and once-weekly INH (900mg).</li>\n</ol>\n<p>\n Exploratory Objectives</p>\n<ol>\n <li>\n To quantify RPT and desRPT concentrations in breast milk of postpartum women receiving once- weekly RPT + INH</li>\n</ol>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n 1.      Age ≥ 18 years at screening and able and willing to provide written informed consent for study. However, for the Kericho site, pregnant women <18 years of age can be enrolled since the Kenyan Ethics Review Committee guidelines considers a pregnant woman who is <18 years of age a mature minor and is permitted to give consent for herself and her child without the permission of her parents.</p>\n<p>\n 2.      At screening, evidence by ultrasound of a viable singleton pregnancy with an estimated gestational age at enrollment of ≥ 14 weeks through ≤ 34 weeks as per screening ultrasound.</p>\n<p>\n 3.      Has at least one of the following risk factors for TB:</p>\n<p style=\"margin-left:.75in;\">\n ·         Per participant report, household contact* with a known active pulmonary TB patient</p>\n<p style=\"margin-left:.75in;\">\n ·         Per medical records, confirmation of HIV-1 infection (see Section 4.1.5 of the core protocol) with single positive TST or IGRA at any time in the past. If not available in medical record, perform at screening</p>\n<p>\n 4.      Documentation of HIV-1 infection status, or confirmation of HIV-1 infection status (if unknown or undocumented.</p>\n<p>\n 5.      If HIV-1-infected, documented current prescription of EFV + 2 NRTI regimen and reports taking regimen for at least two weeks prior to enrollment (regimens containing protease, integrase, or entry inhibitors are not permitted)</p>\n<p>\n 6.      Documented laboratory values obtained within 30 days prior to enrollment:</p>\n<p style=\"margin-left:.75in;\">\n ·         Hemoglobin ≥ 7.5 g/dL</p>\n<p style=\"margin-left:.75in;\">\n ·         ALT <u><</u> 3 times the upper limit of normal (ULN)</p>\n<p style=\"margin-left:.75in;\">\n ·         Total bilirubin <u><</u> 2.5 times the ULN</p>\n<p style=\"margin-left:.75in;\">\n ·         Absolute neutrophil count (ANC) ≥ 750 cells/mm3</p>\n<p style=\"margin-left:.75in;\">\n ·         Platelet count <u>></u> 100,000/mm3</p>\n<p>\n 7.      Per participant report at screening, intent to remain in the current geographical area of residence for the duration of the study.</p>\n<p>\n 8.      Per participant report at screening, able to swallow whole tablets</p>\n<p>\n 9.      Per participant report, intention to keep the pregnancy.</p>\n<p>\n 10.  Per participant report, willingness to permit infant to participate in the study</p>\n
      • principal_exclusion_criteria<p>\n 1.      Women who meet any of the following criteria will be excluded from this study:</p>\n<p>\n 2.      Evidence of confirmed or probable active TB disease per WHO symptom screen and confirmation by Gene Xpert, shielded chest x-ray, or sputum sample.</p>\n<p>\n 3.      Participant report of personal history of INH- or rifampin-resistant, multi-drug resistant (MDR), or extensively drug-resistant (XDR) TB.</p>\n<p>\n 4.      Participant report of personal history of active TB in the past 2 years.</p>\n<p>\n 5.      Participant report of previous treatment for LTBI</p>\n<p>\n 6.      Household contact (as defined above) with known active MDR or XDR TB disease.</p>\n<p>\n 7.      Known major fetal abnormality as detected on ultrasound.</p>\n<p>\n 8.      Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.</p>\n<p>\n 9.      Known history of liver cirrhosis at any time prior to study entry.</p>\n<p>\n 10.  Per participant report and/or medical records, evidence of acute clinical hepatitis, such as a combination of abdominal pain, jaundice, dark urine, and/or light stools within 90 days prior to entry.</p>\n<p>\n 11.  Participant report and/or medical records of peripheral neuropathy Grade 2 or higher within 90 days prior to entry</p>\n<p>\n 12.  Current use or history of active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.</p>\n<p>\n 13.  Participant report and/or clinical evidence of porphyria.</p>\n<p>\n 14.  Any other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives, including taking the study medication.</p>\n<p>\n 15.  Planned or current participation in an interventional drug study.</p>\n<p>\n 16.  Current use of any prohibited or precautionary medications (see Section 5.5 of the core protocol), including didanosine (DDI) or stavudine (D4T)</p>\n
      • primary_end_points<p>\n Primary endpoints</p>\n<p>\n 1. Estimates of CL/F, absorption, and volume of distribution of RPT and its desacetyl-rifapentine metabolite (desRPT).</p>\n<p>\n 2. Maternal safety</p>\n<p>\n 3. Infant safety</p>\n<p>\n Secondary endpoints</p>\n<div>\n 1. Vd, CL/F, Ka for pregnant women in their second or third trimester.</div>\n<div>\n 2. RPT and desRPT concentrations in infants born to women receiving once-weekly RPT + INH.</div>\n<div>\n 3. Tolerability</div>\n<div>\n       o Permanent discontinuation of study drug regimen (i.e., RPT, INH, and pyridoxine)</div>\n<div>\n       o All AEs leading to permanent discontinuation of study drug regimen (i.e., RPT, INH, and pyridoxine)</div>\n<div>\n 4. RPT and des-RPT concentrations in breast milk of postpartum women receiving once-weekly RPT + INH.</div>\n<div>\n 5. Incidence of active TB in mother-infant pairs up to 24 weeks postpartum.</div>\n<div>\n 6. Estimates of CL/F, absorption, and volume of distribution of INH</div>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy1
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • 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 See section on Site Investigators and Contact Information of the Site Specific Addendum and Section 5.1 of the SSA, Kericho site and Population Description</p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n Walter Reed Army Institute of Research IRB </p>\n
      • other_details_regulatory_approved<p>\n KEMRI SERU approved through letter dated 17 August 2016</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_durationThe site estimated duration of accrual is 1 year and each participant will be followed up for 24 weeks postpartum
      • design_controlled_randomisedNo
      • 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_comparatorRifapentine, Isoniazid
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKenya Medical Research Institute Walter Reed project
      • single_site_physical_addressHospital Road, P.O Box 1357-20200
      • single_site_contact_personDeborah Langat
      • single_site_telephone254 5220 30686
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states7
      • number_of_sites
      • multi_country_listKenya, Haiti, Thailand, Malawi, Zimbabwe, South Africa, United States
      • data_monitoring_committeeYes
      • total_enrolment_per_site20
      • total_participants_worldwide82 pregnant women and their infants
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornYes
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • 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_nameLorner
      • investigator1_middle_nameChepkoech
      • investigator1_family_nameSoy
      • investigator1_qualificationRN
      • investigator1_professional_addressKEMRI Walter Reed Project P.O Box 1357- 20200, Kericho
      • investigator1_telephone254 5220 30686
      • investigator1_emailLorner.soy@usamru-k.org
      • organisations_transferred_Yes
      • number_participants20
      • notification<p>\n no</p>\n
      • approval_date27-10-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted28-02-2020
      • 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:42px;\">\n <p>\n <strong>B. Reason study was not started or was closed prior to completion or is being transferred to another institution:</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:28px;\">\n <p>\n N/A</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:24px;\">\n <p>\n <strong>C. Provide a summary of research objectives:</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:79px;\">\n <p>\n This was a multicenter study and the target sample for all the international sites was 50 mother infant pairs. Kericho site was to enroll up to 20 mother infant pairs but due to competitiveness in terms of enrollment, Kericho site enrolled 7 mother infant pairs but all the sites achieved the target sample size of 50 mother infant pairs.</p>\n <h2>\n Primary Objective</h2>\n <ol>\n <li>\n To estimate the population pharmacokinetics (PK) (CL/F, absorption, volume of distribution) of RPT and its desacetyl-rifapentine metabolite (desRPT) among pregnant women during the second trimester and third trimester who are receiving once-weekly RPT (900mg or the new study dose, if a dose adjustment is indicated by the interim analysis) and once-weekly INH (900mg).</li>\n <li>\n To estimate the incidence of serious adverse events (SAEs) related to RPT + INH dosed once weekly for 12 weeks in pregnant women.</li>\n <li>\n To describe the infant safety outcomes among infants born to women receiving once-weekly RPT + INH.</li>\n </ol>\n <p>\n <strong><em>Secondary</em></strong><strong><em> Objectives</em></strong></p>\n <ol>\n <li>\n To estimate the population pharmacokinetics (PK) (CL/F, absorption, volume of distribution) of RPT and its desacetyl-rifapentine metabolite (desRPT) among pregnant women during the postpartum period who are receiving once-weekly RPT (900mg or the new study dose, if a dose adjustment is indicated by the interim analysis) and once-weekly INH (900mg).</li>\n <li>\n To assess the impact of covariates (gestational age, weight, age, HIV status) on primary PK.</li>\n <li>\n To compare RPT and desRPT exposure pharmacokinetic parameters (AUC, Cmax, Cmin) for RPT in pregnant and postpartum women versus non-pregnant historical controls, using non-compartmental analyses.</li>\n <li>\n To determine the RPT dose in pregnancy that achieves similar estimated exposure (AUC) of RPT.</li>\n <li>\n To quantify RPT and desRPT concentrations at delivery among infants born to women receiving once-weekly RPT + INH.</li>\n <li>\n To describe the tolerability of RPT + INH dosed once weekly for 12 weeks in pregnant and postpartum women.</li>\n <li>\n To assess incidence of active TB in mother-infant pairs up to 24 weeks postpartum.</li>\n <li>\n To explore the population pharmacokinetics (PK) (CL/F, absorption, volume of distribution) of INH in HIV-1-infected and HIV-1-uninfected pregnant and postpartum women (i.e., women who are and are not taking efavirenz (EFV)) who are receiving once-weekly RPT (900mg or the new study dose, if a dose adjustment is indicated by the interim analysis) and once-weekly INH (900mg).</li>\n <li>\n To quantify RPT and desRPT concentrations in breast milk of postpartum women receiving once- weekly RPT + INH.</li>\n </ol>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:46px;\">\n <p>\n <strong>D. 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 The Kericho site was activated to start screening and enrollment on 19 June 2017 after all approvals and study drugs were received on site.  A total of 8 pregnant women were screened and 7 pregnant women (and their infants) enrolled. One pregnant woman who was screened was not eligible for the study. All the 7 mothers and their infants completed and exited the study as per the protocol. Total accrual from all sites was 50 mother infant pairs.</p>\n <p>\n  </p>\n <p>\n This was a Phase I/II trial evaluating the pharmacokinetics and safety of once-Weekly Rifapentine and Isoniazid among pregnant women with indications for tuberculosis preventative therapy in Haiti, Kenya, Malawi, Thailand, and Zimbabwe (NCT02651259). Isoniazid and rifapentine were provided at standard doses (900mg weekly) for 12 weeks. Pharmacokinetic sampling was performed with the first (2nd/3rd trimester) and twelfth (3rd trimester/postpartum) doses. Non-linear mixed effects models were used to estimate drug population pharmacokinetics</p>\n <p>\n  </p>\n <p>\n Of 50 participants, 20 had HIV and were taking efavirenz-based antiretroviral therapy. Among women without HIV, clearance of rifapentine was 28% lower during pregnancy than postpartum (1.20 vs. 1.53 L/h, p<0.001), with area under the concentration-time curve (AUCSS) of 786 and 673 mg*hr/L, respectively. In pregnant women with HIV, clearance was 30% higher than women without HIV (p<0.001), resulting in a lower AUCss (522 mg*h/L); clearance did not change significantly between pregnancy and postpartum. Pregnancy did not impact isoniazid pharmacokinetics. There were no drug-related serious adverse events, treatment discontinuations, or TB cases in women or infants</p>\n <p>\n The study found that the regimen of weekly isoniazid and rifapentine for three months (3HP) does not require dose adjustment in pregnancy. Rifapentine clearance is higher among women with HIV, but all women achieved exposures of rifapentine and isoniazid associated with successful tuberculosis prevention. The data support proceeding with larger safety-focused studies of 3HP in pregnancy</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;height:41px;\">\n <p>\n <strong>E. 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:48px;\">\n <ul style=\"list-style-type:circle;\">\n <li>\n Oral abstracts on Rifapentine Pharmacokinetics and Safety in pregnant women with and without HIV on 3HP was presented on the March 8^th - 11^th March 2020 at the Conference on Retroviruses & Opportunistic Infections (CROI).</li>\n <li>\n Manuscript on Pharmacokinetics and Safety of Three Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women.</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=\"6\">\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>G. 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>H. 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:27px;\">\n <table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:646px;height:18px;\">\n <p>\n Please find attached P2001 Study Product Recovery Report.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:646px;height:5px;\">\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>I. 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:43px;\">\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 SERU 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 IMPAACT -approved TB/HIV related research. 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 KEMRI SERU.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:702px;\">\n <p>\n <strong>J. 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>K. 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:81px;\">\n <p>\n Yes, from the Publication:</p>\n <ul style=\"list-style-type:circle;\">\n <li>\n There is no dose adjustment of rifapentine and isoniazid required in pregnancy.</li>\n <li>\n The regimen of weekly isoniazid and rifapentine for three months for tuberculosis prevention was well-tolerated in pregnant women, and target concentrations of both drugs were achieved at standard doses among women with and without HIV.</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n  </p>\n
      • implication_results<p>\n Yes, from the Publication:</p>\n<ul style=\"list-style-type: circle;\">\n <li>\n There is no dose adjustment of rifapentine and isoniazid required in pregnancy.</li>\n <li>\n The regimen of weekly isoniazid and rifapentine for three months for tuberculosis prevention was well-tolerated in pregnant women, and target concentrations of both drugs were achieved at standard doses among women with and without HIV.</li>\n</ul>\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_siteFind attached product accountability documents
      • final_date0000-00-00
      • modified2023-04-28 10:39:27
      • created2016-08-24 09:43:12
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id351
        • application_id539
        • given_nameDeborah
        • middle_nameChepngeno
        • family_nameLangat
        • qualificationMBChB, MSc, DLSHTM
        • professional_addressKEMRI Walter Reed Project P.O Box 1357- 20200, Kericho
        • telephone254 5220 30686
        • emailDeborah.langat@usamru-k.org
        • created2016-08-24 09:59:06
        • modified2020-02-28 12:24:43
    • SiteDetail(array)
      • 0(array)
        • id418
        • application_id539
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2016-08-24 09:59:06
        • modified2020-02-28 12:24:43
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id279
        • application_id539
        • sponsorThe National Institute of Allergy and Infectious Diseases
        • sponsor_typeResearch Institution
        • contact_personEllen Townley
        • addressMaternal Adolescent Pediatric Branch HJF DAIDS, DAIDS/NIAID/NIH 5601 Fishers Lane Room 8B37
        • telephone_number240-292-4784
        • fax_number240-627-3465
        • cell_number240-292-4784
        • email_addressellen.townley@nih.gov
        • created2016-08-24 09:59:06
        • modified2020-02-28 12:24:43
  • 3(array)
    • Application(array)
      • id537
      • user_id342
      • trial_status_id(null)
      • abstract_of_study<p>\n Oral zinc sulphate solution has a bad taste and therefore children do not accept it easily. This study is required to show that a new formulation of zinc sulphate is better accepted by children. If this is the case, the formulation will improve the management of childhood diarrhoea which is a major cause of morbidity and mortality in Kenya. It is hoped that this study will provide insight on determinants of acceptability and adherence to zinc supplemtantion. This would feed into thee design of interventions that would promote acceptability and eventually reduce the duration and the severity of diarrhoea. If the formulation has a superior acceptability compared to ORS then this would provide insights into the development of better formulations.</p>\n
      • study_title<p>\n Zeenk Acceptability Study</p>\n
      • laymans_summary(null)
      • short_titleZeenk study
      • protocol_noECCT/16/08/02
      • version_no9/2015
      • date_of_protocol09-08-2015
      • study_drugZinc sulphate
      • disease_conditionAcute dirrhoea
      • 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_nameZinc sulphate
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressquality@ucl.co.ke
      • 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_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 George Muriithi 0786911530
      • declaration_date102-08-2016
      • declaration_principal_investigatorDr Faith Apolot Okalebo
      • declaration_date202-08-2016
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<p class=\"Corpsdetextemarge\">\n <span lang=\"EN-GB\" style=\"font-size:11.0pt\">Diagnosis: Acute diarrhoea not requiring admission<o:p></o:p></span></p>\n<p class=\"Corpsdetextemarge\">\n <span lang=\"EN-GB\" style=\"font-size:11.0pt\">Sex:         Male and female<o:p></o:p></span></p>\n<p class=\"Corpsdetextemarge\">\n <span lang=\"EN-GB\" style=\"font-size:11.0pt\">Age:        18-59 months<o:p></o:p></span></p>\n<p class=\"Corpsdetextemarge\">\n <span lang=\"EN-GB\" style=\"font-size:11.0pt\">Care-giver: Ability by the caregiver to comprehend and willingness to sign statement of informed consent. <o:p></o:p></span></p>\n
      • principal_exclusion_criteria<p>\n Severe dehydration requiring admission</p>\n<p>\n Does not meet any of the inclusion criteria</p>\n
      • primary_end_points<p>\n The treatment will be considered to have good acceptability if 80% of the prescribed treatment is taken by at least 70% of the children.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • 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 10</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 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_duration6 Months
      • design_controlled_randomisedNo
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overYes
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorORS
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites2
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site300
      • total_participants_worldwiden/a
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyChildren
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameFaith
      • investigator1_middle_nameApolot
      • investigator1_family_nameOkalebo
      • investigator1_qualificationB. Pharm, Phd
      • investigator1_professional_addressUniversity of Nairobi P O Box 19676 – 00202
      • investigator1_telephone0737 434204
      • investigator1_emailokalebo@yahoo.com
      • organisations_transferred_No
      • number_participants600
      • notification
      • approval_date10-08-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted08-08-2016
      • 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)
      • modified2016-08-10 08:43:23
      • created2016-08-01 10:29:07
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id347
        • application_id537
        • given_nameMargaret
        • middle_name
        • family_nameOluka
        • qualificationB. Pharm, Phd
        • professional_addressUniversity of Nairobi P O Box 19676 – 00202 Nairobi, Kenya
        • telephone0722 604216
        • emailmargaoluka@yahoo.com
        • created2016-08-01 10:47:45
        • modified2016-08-08 09:39:18
      • 1(array)
        • id348
        • application_id537
        • given_nameDavid
        • middle_name
        • family_nameKimutai
        • qualificationMBChB, M.Med (Paeds)
        • professional_addressMbagathi District Hospital Ngumo Estate
        • telephone0722975048
        • emaildkimutaidr@yahoo.com
        • created2016-08-01 10:47:45
        • modified2016-08-08 09:39:18
      • 2(array)
        • id349
        • application_id537
        • given_nameCaren
        • middle_name
        • family_nameEmadu
        • qualificationMBChB, M.Med (Paeds)
        • professional_addressMama Lucy Kibaki Hospital Kayole
        • telephone0722919084
        • emailemaduuc@gmail.com
        • created2016-08-01 10:47:45
        • modified2016-08-08 09:39:18
    • SiteDetail(array)
      • 0(array)
        • id414
        • application_id537
        • county_id47
        • site_nameMbagathi District Hospital
        • physical_addressMbagathi District Hospital Ngumo Estate Mbagathi Way Nairobi- Kenya
        • contact_details0722975048
        • contact_personDavid Kimutai
        • site_capacity(null)
        • misc(null)
        • created2016-08-01 10:47:45
        • modified2016-08-08 09:39:18
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id417
        • application_id537
        • county_id47
        • site_nameMama Lucy Kibaki Hospital
        • physical_addressMama Lucy Kibaki Hospital Kayole Nairobi- Kenya
        • contact_details0722919084
        • contact_personCaren Emadu
        • site_capacity(null)
        • misc(null)
        • created2016-08-02 11:19:30
        • modified2016-08-08 09:39:18
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id277
        • application_id537
        • sponsorUNIVERSAL CORPORATION LTD
        • sponsor_type(null)
        • contact_person
        • addressP.O. Box 1748-00902
        • telephone_number254202700632
        • fax_number
        • cell_number0733513075
        • email_addresspalu@ucl.co.ke
        • created2016-08-01 10:47:45
        • modified2016-08-08 09:39:18
  • 4(array)
    • Application(array)
      • id531
      • user_id32
      • trial_status_id5
      • abstract_of_study<h2>\n <span style=\"font-size: 12px;\">Title: Menstrual cups and cash transfer to reduce sexual and reproductive harm and school dropout in adolescent schoolgirls in western Kenya: a cluster randomised controlled trial.</span></h2>\n<p>\n Short Title: Cups or cash for girls (CCg) trial</p>\n<p>\n Background and rationale: Adolescence is a critical time of psychological and biological change, and advocacy has increased to identify interventions that protect against sexual and reproductive health (SRH) harms, which are disproportionately high among adolescent girls in sub-Saharan Africa. In much of eastern and southern Africa including western Kenya, where unprotected transactional sex is common, young females are highly vulnerable to sexually transmitted infections (STIs), including HIV, and pregnancy resulting in school dropout. While the burden of young female SRH harms is high for individuals, communities and health services, sustainable preventive interventions are lacking. Evidence of a positive association between girls’ education, health and economic potential has strengthened international resolve to improve educational opportunities for adolescent girls. While SRH education has minimal impact on SRH harms, staying in school has shown to protect girls against early marriage, teen pregnancy, and HIV infection, with schoolgirls reporting less frequent sex, and fewer partners with less age disparity. While MDGs focused on primary school attendance, the post-2015 Sustainability Development Goals continue to encourage investment in secondary, tertiary and vocational education to build human capital, innovation and economic growth, but require the support of cost-effective interventions. Interventions using cash transfer (CT) have demonstrated a protective effect on girls SRH (HIV, HSV-2, sexual behaviours, and school indicators)^1-3. Menstrual hygiene management (MHM) is a pervasive problem across low middle income countries (LMICs) and a lack of MHM materials and facilities negatively impact girls’ school-life. This increases girls’ vulnerability to coercive sex, which often creates a pathway to obtain necessities such as soap, sanitary products, and underwear; 10% of 15 year old girls report that they obtain money through sex to purchase sanitary products in western Kenya.⁴To tackle these challenges, our team ran a pilot menstrual study in western Kenya. It provided MHM tools to adolescent girls in the form of reusable menstrual cups and disposable sanitary pads. The results demonstrated a lower prevalence of STI and bacterial vaginosis among girls who were provided with a single menstrual cup (one cup can last up to 10 years), and a lower prevalence of school dropout after 12 months follow-up compared to controls.⁵This pilot requires replication in a larger trial population with longer follow-up. Comparison against CT offers an opportunity to examine the efficacy and cost-effectiveness of these different approaches to improve girls’ life-chances in rural western Kenya. The study is designed to inform evidence-based policy to improve girls’ health, school equity and their life-chances.</p>\n<p>\n Primary objective: To determine the impact of menstrual cups alone, cash transfer alone, or the two in combination, in secondary schoolgirls on a composite of deleterious outcomes (HIV, HSV-2 infection, or school dropout).</p>\n<p>\n Hypothesis: We postulate the interventions tested will break the cycle of sexual and reproductive ill-health, under-achievement, and poverty which impede girls’ successful completion of school.</p>\n<p>\n Overview Study Design: Single site open-label 4-arm, school-cluster randomised controlled superiority trial. Schools are the unit of randomisation (clusters), with girls the unit of measurement. Schools will be randomly allocated into 4 arms using a 1:1:1:1 ratio and permuted block randomisation to minimise bias. Enrollment will be staggered over 2 school terms if logistically required. Girls will be followed-up through graduation and into employment or up to 10 academic terms to determine if they complete secondary school (Form 4). Sealed, opaque envelopes will be prepared with the study allocation. Counsellors conducting HIV and HSV-2 testing, and laboratory technicians will be blinded to the study arm. Field staff who conduct home visits to confirm dropout will also be masked where feasible.</p>\n<p>\n Sites: The study will be conducted in in Siaya County, western Kenya. Dependent on the recruitment rate, enrolment will be expanded to other neighboring counties.</p>\n<p>\n Study Population: Secondary schoolgirls who attend 84 eligible schools in the western Kenya study site. Girls wil be residents of the area, with a history of established menses (>=3 times), no disability preventing participation, with parent or guardian’s consent and girl’s assent. Girls attending bording schools or with visible/declared pregnancy will be excluded at baseline.</p>\n<p>\n Study Interventions: 1. One menstrual cup (Mooncup®) with handwash soap termly; 2. Cash transfer (CT; girls’ pocket money) via local community/mobile banking with financial literacy; 3. A combination of cup and CT interventions; 4. ‘Usual practice’ (control) with handwash soap termly.</p>\n<p>\n Outcome Measures: Primary efficacy outcome: Composite endpoint comprised of incident HIV, HSV-2, and all-cause school dropout, by end of study. Key secondary outcomes include incident HIV, HSV-2, school dropout, BV and reported sexual behaviours including pregnancy, quality of life measures, school indicators (performance, grade repitition, re-enrolment, absence), and cost-effectiveness. Primary safety outcome measure: toxic shock syndrome (TSS), and severe violence associated with intervention. Key secondary safety outcome include contamination on menstrual cups and other emergent harms associated with the interventions.</p>\n<p>\n Follow-up procedures: HIV and HSV-2 serostatus will be assessed at baseline and around the time of final school term (Form 4), with interim testing or annual testing if funding allows, including for bacterial vaginosis and other STI. School dropout will be assessed every term until the end of Form (class) 4. Other endpoints will be evaluated at baseline and following completion of behavioural surveys each intervention year. Safety monitoring of TSS and physical violence will be conducted throughout by study nurses, supplemented by health facility registry reviews and evaluation of HDSS census mortality data.</p>\n<p>\n Sample size: Main trial: 3864 participants (in 4 arms; 966 per arm), in 84 clusters (21 schools per arm).</p>\n<p>\n Data Analysis: Primary trial analyses will be based on the intention to treat principle and a secondary analyses will also be done on the per protocol population. Generalised estimating equation (GEE) log binomial models will be used to analyse the primary endpoint and its components. The GEE model will include the arm as a fixed effect and school as a cluster effect. The RR values for the 5 pre-specified primary comparisons together with their 95% confidence intervals will be derived from the GEE model. The secondary endpoints will be analysed similarly using GEE models. For GEE analysis of a continuous endpoint such as quality of life, normal distribution and identity link functions will be used. For GEE analysis of a binary outcome (such as having an event of STI, HIV, pregnancy, or school dropout), binomial distribution and log link functions will be used; for GEE analysis of recurrence of events (such as number of sexual partners during a specific time), Poisson distribution and log link functions will be used. Covariate adjusted analysis of primary endpoint will be performed within the GEE framework with treatment as the study variable, and other predictors as covariates, and school as cluster effect. For qualitative analysis, FGD recordings will be transcribed verbatim with back translation. Transcripts will analysed using thematic analysis by study group, 2 researchers will separately assign codes for emergent themes, subthemes patterns, and associations using NVIVO with intercoder reliability checked and consensus reached following discussion. As themes emerge, differences and similarities will be compared across trial arms, and between study groups. Qualitative data from in depth interviews will be similarly evaluated.</p>\n<p>\n Partner institutions: KEMRI and CDC Collaboration, Kisumu, western Kenya; Kenya Ministries of Education and Health, Liverpool School of Tropical Medicine; US Centers for Disease Control and Prevention; Safe Water and AIDS Project.</p>\n<p>\n Funding: Joint Global Health Trials (Department for International Development, Medical Research Council, Wellcome Trust), UK.</p>\n
      • study_title<p>\n Menstrual cups and cash transfer to reduce sexual and reproductive harm and school dropout in adolescent schoolgirls in western Kenya: a cluster randomised controlled trial</p>\n
      • laymans_summary<p>\n Adolescent girls in impoverished settings suffer from inadequate menstrual hygiene to manage their periods. Lack of materials result in girls’ poor engagement with schooling, or miss schooling due to stigma and shame, and can lead to an increase in reproductive tract infections due to poor hygiene. As a consequence, girls may seek to acquire menstrual products from boys and men, placing them at increased risk of sexual infections such as HIV or HSV-2, or pregnancy, which in turn will lead to girls dropping out of school.</p>\n<p>\n  </p>\n<p>\n <strong>We conducted a study among 4137 adolescent girls attending 96 secondary schools in Siaya County, rural western Kenya. We provided a menstrual product (a menstrual cup), or pocket money, or both to girls (allocated by school), and compared their ‘outcomes’ with girls not provided an intervention until the end of the project (these girls then received a menstrual cup). Our results indicate that the menstrual cup was effective in supporting girls’ menstrual hygiene at school without any serious adverse outcomes. We found girls who used cups had lower rates of HSV-2 infection, and school dropout, and a reduction in the rate of pregnancy while in school. Girls receiving the cup and pocket money also had a reduction in dropout but pocket money alone did not improve girls’ health or schooling outcomes. No serious adverse effects occurred with provision of the cup or pocket money to girls. These findings suggest a menstrual product like a menstrual cup can greatly improve schoolgirls sexual and reproductive health and help them complete their secondary school education.</strong></p>\n
      • short_titleCups or Cash for Girls Trial
      • protocol_noECCT/16/07/06
      • version_nov1.2-14 April 2016
      • date_of_protocol14-04-2016
      • study_drugMenstrual cup v cash transfer
      • disease_conditionSexual and reproductive health
      • 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_nameMenstrual cup (Mooncup®)
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresstsang@kemricdc.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_impd1
      • applicant_prev_data0
      • 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_applicantDr Daniel Kwaro, local PI
      • declaration_date125-07-2016
      • declaration_principal_investigatorDr Penelope Phillips-Howard PI, Liverpool School of Tropical Medicine
      • declaration_date225-07-2016
      • placebo_presentNo
      • study_objectives<div>\n AIM AND OBJECTIVES</div>\n<ul>\n <li>\n The overall aim is to inform evidence-based policy to develop intervention programmes which improve adolescent girls’ health, school equity and life-chances.</li>\n</ul>\n<div>\n PRIMARY OBJECTIVE</div>\n<ul>\n <li>\n To determine the impact of menstrual cups or cash transfer alone, or in combination, provided to secondary schoolgirls, on a composite of deleterious outcomes (HIV, HSV-2 infection, and school dropout).</li>\n</ul>\n<div>\n SECONDARY OBJECTIVES</div>\n<ol>\n <li>\n To measure the age-specific differences in the acquisition of HIV and HSV-2 infections in secondary schoolgirls and risk factors for incident HIV and HSV-2 infections.</li>\n <li>\n To determine the risk, risk factors and reasons for dropout and other school indicators among secondary schoolgirls examining the influence of social, epidemiological, and/or health characteristics.</li>\n <li>\n To determine the cost benefit of menstrual cup and CT programmes for schoolgirls by assessing the cost savings of outcomes averted, for individual and combined interventions, and resulting societal impact.</li>\n <li>\n To determine the safety of menstrual cups use, including risk of cup contamination over time, serious adverse events, and identify factors that increase or modify this risk.</li>\n <li>\n To determine factors affecting how adolescent girls spend CT money, and what training is required to support their financial literacy and decision-making.</li>\n <li>\n To determine any adverse outcomes associated with CT and evaluate ways to mitigate risk.</li>\n <li>\n To determine the impact of the interventions on girls' sexual behaviours, including age of sexual début, coerced sex, number of partners, age of partners, pregnancy, condom use and use of contraception.</li>\n <li>\n To examine programme implementation for interventions in schools, working with beneficiaries and stakeholders to develop programme implementation packages.</li>\n <li>\n If funding is available, examine the effect of interventions on other sexually transmitted infections and bacterial vaginosis.</li>\n</ol>\n
      • principal_inclusion_criteria<div>\n Inclusion criteria for schools</div>\n<ul>\n <li>\n • Secondary school in study area</li>\n <li>\n • Girls or co-educational school</li>\n <li>\n • Day school</li>\n <li>\n • Approval by Head Teacher in consultation with teachers, parents, and students</li>\n</ul>\n<div>\n Inclusion criteria for participants</div>\n<ul>\n <li>\n Attend secondary day schools in the study area at enrolment</li>\n <li>\n Resident of the study area</li>\n <li>\n Have a history of established menses (>=3 times)</li>\n <li>\n Have no disability preventing participation i.e. school for the blind</li>\n <li>\n Have received parent or guardian’s consent and assent to participation.</li>\n</ul>\n<div>\n  </div>\n
      • principal_exclusion_criteria<div>\n <div>\n Exclusion criteria for schools</div>\n <ul>\n <li>\n Boys only school</li>\n <li>\n Boarding schools</li>\n <li>\n Special needs schools (i.e. for the blind)</li>\n </ul>\n</div>\n<div>\n Exclusion criteria for participants</div>\n<ul>\n <li>\n Attend boarding schools</li>\n <li>\n Pregnant at time of enrolment (declared or confirmed)</li>\n <li>\n Parental or own refusal</li>\n</ul>\n
      • primary_end_points<p>\n Composite endpoint comprised of incident HIV, HSV-2, and all-cause school dropout, by end of study.�</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyTo examine if provision of a menstrual product, or pocket money reduces girls need to engage in transactional sex to obtain sanitary hygiene or other essential items, thus reducing school dropout or sexual risks, compared with girls under usual practice.
      • 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 � Principal Investigators - adolescent sexual health and menstruation - Dr Penelope Phillips-Howard; clinician and HIV/HSV-2 specialist Dr� Daniel Kwaro (both � � � � have been PI on numerous studies).</p>\n<p>\n � � Study Coordinator,� Elizabeth Nyothach,� programme management experience, ran pilot study</p>\n<p>\n � � Data Manager and supervising head of demographic surveillance</p>\n<p>\n � � Trial Statistician and 1 senior data manager providing trial statistical support and oversight</p>\n<p>\n � � Pharmaco-vigilance supervision, expert in adverse event monitoring ; and Annemeike van Eijk clinician</p>\n<p>\n � � Full time on-site study nurses, experts in adolescent sexual and reproductive health, girls menstruation and menstrual cup use</p>\n<p>\n � � Laboratory technologists at KEMRI</p>\n<p>\n � � HIV testing and counselling survey staff , experts in HIV TC including in adolescents</p>\n<p>\n � � Community interviewers, experts in field surveys</p>\n<p>\n � � Qualitative field workers, experts in focus group discussions</p>\n<p>\n � � Implementation experts to provide training on use of interventions to girls in school</p>\n<p>\n � � Field survey staff experienced in Water and Sanitation assessments for schools</p>\n<p>\n � � Other support (academic) - health economics, clinical epidemiologists, HIV, HSV2, laboratory experts.</p>\n<p style=\"margin-left:18.0pt;\">\n Other support (local experts and field) � - local community health workers; and linkage with health facilities; ministry of health and education�</p>\n
      • other_details_explanation<p style=\"margin-left:27.75pt;\">\n Schoolgirls in rural Siaya County have no access to menstruation, this places them at risk of seeking money through transactional sex to obtain sanitary products; by providing menstrual cups (or cash) the trial hypothesises this reduces their risk of sexual exposure; thus reduces their risk of sexual and reproductive harms (such as HIV, and HSV-2 sexually transmitted infections), and drop out from school.�</p>\n
      • other_details_regulatory_notapproved<p>\n Liverpool School of Tropical Medicine (LSTM) IRB (13 July 2016)</p>\n
      • other_details_regulatory_approved<div>\n �</div>\n<div>\n <span style=\"font-family: Arial, sans-serif; font-size: 16px; line-height: 18.4px; text-indent: -24px;\">Kenya Medical Research Institute (KEMRI)-SERU-12-May-2016</span></div>\n<div>\n �</div>\n<div>\n <span style=\"font-family: Arial, sans-serif; font-size: 16px; line-height: 18.4px;\">Centers for Disease Control and Prevention USA (CDC) IRB -31-May-2016</span></div>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration3.3 years
      • 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_comparatorgirls using their usual p
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaSiaya County
      • single_site_physical_addressKenya Medical Research Institute, PO Box 1578
      • single_site_contact_personDr Daniel Kwaro
      • single_site_telephone0700 858 288
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site3864
      • total_participants_worldwide3864
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifythe subjects who are under 18 years (minors) will give assent after their parents have given consent
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_namePenelope
      • investigator1_middle_nameAnne
      • investigator1_family_namePhillips-Howard
      • investigator1_qualificationPhD
      • investigator1_professional_addressDepartment of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, L3 5QA, Liverpool, UK, and Kenya Medical Research Institute (KEMRI) Centre for Global Health Research, P.O.Box 1578, 40100 Kisumu
      • investigator1_telephonemobile 0702 126 188; UK mobile +44 798 543 1005
      • investigator1_emailPenelope.Phillips-Howard@lstmed.ac.uk
      • organisations_transferred_Yes
      • number_participants3864
      • notification<p>\n Menstrual cups are available throughout the world, with at least 25 brands used by many millions of girls and women, including in the USA, Europe, countries of sub-Saharan Africa, India, and south America.  The brand we have chosen, Moocups, has FDA approval, is made to ISO international standards and is marketed internationally.  It is currently sold wholesale in 55 countries throughout the world - Argentina, Austria, Belgium, Brazil, Chile, Croatia, Czech Republic, Denmark, Ecuador, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Indonesia, Ireland,  Israel, Italy, Kenya, Luxembourg, Malaysia, Mongolia, Namibia, Netherlands, New Zealand, Norway, Peru, Philippines, Poland, Portugal, Réunion, France, Romania, Russia, Singapore, Slovenia, South Africa, South Korea, Spain, Switzerland, UK, Ukraine, Uruguay, Vietnam.</p>\n
      • approval_date19-10-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted17-03-2020
      • 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\" style=\"width:642px;\" width=\"642\">\n <tbody>\n <tr>\n <td style=\"width:151px;height:36px;\">\n <p style=\"margin-left:8.45pt;\">\n Full title of study</p>\n </td>\n <td colspan=\"3\" style=\"width:491px;height:36px;\">\n <p style=\"margin-left:8.75pt;\">\n Menstrual cups and cash transfer to reduce sexual and reproductive harm and school dropout in adolescent schoolgirls in western Kenya: a cluster randomised controlled trial</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:151px;height:51px;\">\n <p style=\"margin-left:8.45pt;\">\n Start date</p>\n </td>\n <td style=\"width:208px;height:51px;\">\n <p>\n Start enrolment 28 Feb 2017</p>\n <p>\n Enrolment closed 6 July 2018</p>\n </td>\n <td style=\"width:85px;height:51px;\">\n <p align=\"center\" style=\"margin-left:-6.75pt;\">\n End date</p>\n </td>\n <td style=\"width:198px;height:51px;\">\n <p>\n Last follow-up 30 June 2021</p>\n <p>\n Data locked 20 May 2022</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:151px;height:27px;\">\n <p style=\"margin-left:8.45pt;\">\n Sponsor</p>\n </td>\n <td colspan=\"3\" style=\"width:491px;height:27px;\">\n <p>\n Liverpool School of Tropical Medicine</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:151px;height:27px;\">\n <p style=\"margin-left:8.45pt;\">\n Funder</p>\n </td>\n <td colspan=\"3\" style=\"width:491px;height:27px;\">\n <p>\n MRC/DfID/Wellcome Trust; Joint Global Health Trials (MR/N006046/1)</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:151px;height:18px;\">\n <p style=\"margin-left:8.45pt;\">\n Trial registration no.</p>\n </td>\n <td colspan=\"3\" style=\"width:491px;height:18px;\">\n <p>\n NCT03051789 (Clinical Trials); PACTR202003815291283 (Pan African Registry)</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"4\" style=\"width:642px;height:36px;\">\n <p>\n Few rigorous studies have measured menstrual interventions effect on adolescent girls’ sexual and reproductive harms and schooling. We conducted a 4-arm cluster randomised controlled trial in western Kenya to test if menstrual cups or conditional cash transfers (CT) can reduce the incidence of HIV, HSV-2, and school dropout as a composite primary outcome in secondary schoolgirls. Girls attending a participating school, in an eligible class year, had reached menarche, were not visibly pregnant, resided in the study area and had no disability precluding participation were invited.</p>\n <p>\n  </p>\n <p>\n We enrolled 4137 girls in 96 secondary day schools after parental consent and girls’ assent. Based on randomisation of schools, girls received either one menstrual cup, CT, both CT and a cup, or were controls. All girls received puberty and hygiene training, and interventions were combined with use and safety training. Sociodemographic and behavioural surveys and biomarker data were collected at baseline, midway and at end of study to measure HIV, HSV-2, and associated risk factors. School attendance was monitored via school registers and home visits confirmed if girls dropped out or transferred schools. Adverse event monitoring was conducted throughout the trial. Data were analysed using multi-level generalized linear models and  controlled for baseline covariates. Trial registration: ClinicalTrials.gov NCT03051789.</p>\n <p>\n  </p>\n <p>\n Of 4137 girls enrolled, 4106 completed follow up between 2017 and June 2021. No significant differences were seen in the primary composite outcome between intervention groups and control in the intention-to-treat population, but menstrual cups were protective against HSV-2. In the per protocol population, cups reduced the incidence of the primary composite outcome,  decreased school dropout and pregnancy. Girls using the combined intervention had a decreased risk of school dropout relative to controls. No serious adverse events were associated with either intervention. We conclude that menstrual cups provide schoolgirls protection against school dropout, HSV-2, and pregnancy, and are a valuable intervention for improving girls’ SRH and schooling.</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • implication_results<p>\n <span lang=\"EN-GB\" style=\"font-size: 11pt; font-family: Calibri, sans-serif;\">This trial adds to a limited body of evidence on the effect of menstrual cups and/or conditional cash transfer on girls’ SRH and schooling. Menstrual cups were found to be protective against HSV-2, school dropout, and adolescent pregnancy with no evidence of serious adverse events. These results confirm that menstrual cups can be used by schoolgirls, safely and effectively, and can be considered by policy makers and programmes as a solution to improve girls’ menstrual needs, while helping to reduce sexual and reproductive harms, and improve girls’ chances of completing their schooling. </span></p>\n
      • quantity_imported2873
      • quantity_dispensed2605
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      • balance_site268
      • final_date0000-00-00
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        • id345
        • application_id531
        • given_namePenelope
        • middle_nameAnne
        • family_namePhillips-Howard
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        • professional_addressDepartment of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, L3 5QA, Liverpool, UK, and Kenya Medical Research Institute (KEMRI) Centre for Global Health Research, P.O.Box 1578, 40100 Kisumu,
        • telephonemobile 0702 126 188; UK mobile +44 798 543 1005
        • emailPenelope.Phillips-Howard@lstmed.ac.uk
        • created2016-07-20 15:24:02
        • modified2020-03-17 14:53:37
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        • given_nameDaniel
        • middle_nameOluoch
        • family_nameKwaro
        • qualificationMD
        • professional_addressKenya Medical Research Institute (KEMRI) Centre for Global Health Research, P.O.Box 1578, 40100 Kisumu, Kenya
        • telephonemobile: 0700 858 288
        • emailDKwaro@kemricdc.org
        • created2016-07-25 10:19:50
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        • id276
        • application_id531
        • sponsorLiverpool School of Tropical Medicine
        • sponsor_typeResearch Institution
        • contact_personCarl Henry
        • addressTrial governance, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK
        • telephone_number+44 (0) 151 705 3794
        • fax_number
        • cell_number+44 (0) 7701050237
        • email_addressCarl.Henry@lstmed.ac.uk
        • created2016-07-20 15:24:02
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    • approved2
• $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