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      • abstract_of_study<div>\n Malaria morbidity and mortality have been reduced substantially as malaria control interventions have been scaled up across Africa, including in Kenya. Nonetheless, malaria continues to cause considerable morbidity and mortality, especially in children under 5 years of age living in sub Saharan Africa.  As we aim for a reduction in malaria burden, and towards malaria elimination, it has become clear that new tools to fight malaria are urgently needed. A highly efficacious vaccine would be an important addition to complement current malaria control measures and to contribute to elimination efforts. Among the different vaccine approaches used to prevent malaria infection, whole Plasmodium falciparum sporozoite (PfSPZ) vaccines have shown consistent, high-level protection in a number of phase I clinical trials. </div>\n<div>\n  </div>\n<div>\n The candidate malaria vaccine, PfSPZ Vaccine, consists of aseptic purified, cryopreserved, radiation-attenuated Plasmodium falciparum (Pf) sporozoites, which when given by direct venous inoculation (DVI) to malaria naïve volunteers in the United States was safe, well tolerated and showed dose-dependent, high protection against controlled human malaria infection.  The Kenya Medical Research Institute and the U.S. Centers for Disease Control and Prevention, in collaboration with NIH and Sanaria, propose to conduct a study to measure safety, immunogenicity and efficacy of this novel candidate malaria vaccine when given to infants from 5 to 12 months inclusive.  The study will be conducted in Siaya County in western Kenya. Initially, in Part 1 of the trial, 120 children will be recruited into an age de-escalation and dose escalation study to document safety of the vaccine in three age groups (children aged 5–12 years, children aged 13 – 59 months, and infants aged 5–12 months) and at the following dosages of sporozoites versus placebo: 1.35 x 105, 2.7 x 105, 4.5 x 105, 9.0 x 105 PfSPZ vaccine (only the higher two doses in children aged 5–12 years), given as a single injection by direct venous inoculation (DVI). Part 1, age de-escalation and dose escalation, will begin with administration of 4.5 x 105 PfSPZ in 12 children aged 5–12 years (8 vaccine, 4 placebo), provided to a limited number of participants each day (for example, approximately 3 participants each day on days 1–4).  The PfSPZ Vaccine dose will only be increased to the next level when safety has been assessed in participants of the first group, and earliest at 14 days after the first injection. At this time, the lowest dose (1.35 x 105) will be administered to children age 13-59 months, with doses doubling every two weeks, after assessment of safety signals, until the final dose of 9.0 x 105 PfSPZ is reached. The lowest dose will be administered to infants 5–12 months after this dosage has shown to be safe in 13-59 months-olds, and doses will be doubled every two weeks, after assessment of safety signals, until the dose of 9.0 x 105 PfSPZ is reached. Overall vaccine doses will only be increased if they are assessed as well tolerated and the safety data are acceptable for further evaluation of the vaccine at a higher dose, applicable to all the age groups. All of these proposed doses have been shown to be well tolerated with no serious safety signals in studies in US adults and, in African adults at the two lowest doses.  Therefore, based on the critical importance of dose in mediating protection with this vaccine, the 2 highest dosages found to be well tolerated will be used for the Part 2 of the trial, which will measure safety and efficacy of the PfSPZ vaccine. The highest well tolerated dosage (likely to be 9.0 x 105 PfSPZ) will be administered by DVI 3 times to 104 infants (group 1), and 4 times to 104 infants (group 2); the second highest dosage (likely to be 4.5 x 105 PfSPZ) will be given 3 times to another study arm of 104 infants (group 3) to document a dose response and to understand whether the lower dose is highly efficacious in this age-category.  The rationale for the amount of PfSPZ Vaccine (4.5 x 105  or  9.0 x 105 PfSPZ), number of doses ( 3 or 4) and intervals between doses ( 4 and 8 weeks) is based on data from ongoing studies in US and African adults for conferring durable immunity and protection, and will be further informed by the dose escalation trial. Another group of 104 infants will receive 3 (n=52; group 4) or 4 (n=52; group 5) doses of normal saline (NS) by direct venous injection as placebo. The dosing interval in all 3 dose groups will be 8 weekly (0, 8,16 weeks), while the doses in the 4 dose groups will be given at 0, 4, 8 and 16 weeks. The main objectives of this study are to measure the safety, tolerability and immunogenicity of PfSPZ Vaccine in infants (measured in Part 1 and Part 2 of this trial) and to determine whether PfSPZ Vaccine administered by DVI to infants provides high-level protection (point estimate >60%) against Pf infection during 6 months following the last vaccine dose when compared to a placebo group (Part 2 of the trial).  A secondary objective will be to measure safety tolerability, immunogenicity and efficacy during 12 months follow-up.</div>\n<div>\n  </div>\n
      • study_title<p>\n Safety, Tolerability and Efficacy of PfSPZ Vaccine Administered by Direct Venous Inoculation (DVI) to Healthy Children and Infants 5 Months through 12 Years of Age Living in an Area of High Malaria Transmission in Western Kenya: Age de-escalation and Dose Escalation and a Double Blind, Randomized Placebo-Controlled Trial for Safety and Efficacy</p>\n
      • laymans_summary<div>\n Malaria morbidity and mortality have been reduced substantially as malaria control interventions have been scaled up across Africa, including in Kenya. Nonetheless, malaria continues to cause considerable morbidity and mortality, especially in children under 5 years of age living in sub Saharan Africa.  As we aim for a reduction in malaria burden, and towards malaria elimination, it has become clear that new tools to fight malaria are urgently needed. A highly efficacious vaccine would be an important addition to complement current malaria control measures and to contribute to elimination efforts. Among the different vaccine approaches used to prevent malaria infection, whole Plasmodium falciparum sporozoite (PfSPZ) vaccines have shown consistent, high-level protection in a number of phase I clinical trials. </div>\n<div>\n  </div>\n<div>\n The candidate malaria vaccine, PfSPZ Vaccine, consists of aseptic purified, cryopreserved, radiation-attenuated Plasmodium falciparum (Pf) sporozoites, which when given by direct venous inoculation (DVI) to malaria naïve volunteers in the United States was safe, well tolerated and showed dose-dependent, high protection against controlled human malaria infection.  The Kenya Medical Research Institute and the U.S. Centers for Disease Control and Prevention, in collaboration with NIH and Sanaria, propose to conduct a study to measure safety, immunogenicity and efficacy of this novel candidate malaria vaccine when given to infants from 5 to 12 months inclusive.  The study will be conducted in Siaya County in western Kenya. Initially, in Part 1 of the trial, 120 children will be recruited into an age de-escalation and dose escalation study to document safety of the vaccine in three age groups (children aged 5–12 years, children aged 13 – 59 months, and infants aged 5–12 months) and at the following dosages of sporozoites versus placebo: 1.35 x 105, 2.7 x 105, 4.5 x 105, 9.0 x 105 PfSPZ vaccine (only the higher two doses in children aged 5–12 years), given as a single injection by direct venous inoculation (DVI). Part 1, age de-escalation and dose escalation, will begin with administration of 4.5 x 105 PfSPZ in 12 children aged 5–12 years (8 vaccine, 4 placebo), provided to a limited number of participants each day (for example, approximately 3 participants each day on days 1–4).  The PfSPZ Vaccine dose will only be increased to the next level when safety has been assessed in participants of the first group, and earliest at 14 days after the first injection. At this time, the lowest dose (1.35 x 105) will be administered to children age 13-59 months, with doses doubling every two weeks, after assessment of safety signals, until the final dose of 9.0 x 105 PfSPZ is reached. The lowest dose will be administered to infants 5–12 months after this dosage has shown to be safe in 13-59 months-olds, and doses will be doubled every two weeks, after assessment of safety signals, until the dose of 9.0 x 105 PfSPZ is reached. Overall vaccine doses will only be increased if they are assessed as well tolerated and the safety data are acceptable for further evaluation of the vaccine at a higher dose, applicable to all the age groups. All of these proposed doses have been shown to be well tolerated with no serious safety signals in studies in US adults and, in African adults at the two lowest doses.  Therefore, based on the critical importance of dose in mediating protection with this vaccine, the 2 highest dosages found to be well tolerated will be used for the Part 2 of the trial, which will measure safety and efficacy of the PfSPZ vaccine. The highest well tolerated dosage (likely to be 9.0 x 105 PfSPZ) will be administered by DVI 3 times to 104 infants (group 1), and 4 times to 104 infants (group 2); the second highest dosage (likely to be 4.5 x 105 PfSPZ) will be given 3 times to another study arm of 104 infants (group 3) to document a dose response and to understand whether the lower dose is highly efficacious in this age-category.  The rationale for the amount of PfSPZ Vaccine (4.5 x 105  or  9.0 x 105 PfSPZ), number of doses ( 3 or 4) and intervals between doses ( 4 and 8 weeks) is based on data from ongoing studies in US and African adults for conferring durable immunity and protection, and will be further informed by the dose escalation trial. Another group of 104 infants will receive 3 (n=52; group 4) or 4 (n=52; group 5) doses of normal saline (NS) by direct venous injection as placebo. The dosing interval in all 3 dose groups will be 8 weekly (0, 8,16 weeks), while the doses in the 4 dose groups will be given at 0, 4, 8 and 16 weeks. The main objectives of this study are to measure the safety, tolerability and immunogenicity of PfSPZ Vaccine in infants (measured in Part 1 and Part 2 of this trial) and to determine whether PfSPZ Vaccine administered by DVI to infants provides high-level protection (point estimate >60%) against Pf infection during 6 months following the last vaccine dose when compared to a placebo group (Part 2 of the trial).  A secondary objective will be to measure safety tolerability, immunogenicity and efficacy during 12 months follow-up.</div>\n<div>\n  </div>\n
      • short_titlePfSPZ Malaria Vaccine
      • protocol_noECCT/16/02/05
      • version_no1.0
      • date_of_protocol10-10-2015
      • study_drugPfSPZ Malaria Vaccine
      • disease_conditionMalaria
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_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_data1
      • applicant_stability_data0
      • 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_african0
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan0
      • applicant_contractual_agreement0
      • declaration_applicantDr Tony Sang
      • declaration_date112-02-2016
      • declaration_principal_investigatorDr Martina Oneko
      • declaration_date212-02-2016
      • placebo_presentYes
      • study_objectives<div>\n <strong>Primary objectives:</strong></div>\n<div>\n Part 1: Age de-esclation and dose escalation trial in children and infants (5 months -12 years)</div>\n<div>\n Measure the safety, tolerability and immunogenicity of PfSPZ Vaccine administered at escalating dosages by DVI in older children aged 5–12 years (highest two doses only), younger children aged 13-59 months, and infants 5-12M (at vaccination) at doses of 1.35x105, 2.7x105, 4.5x105, 9.0x105 PfSPZ Vaccine given as a single dose.</div>\n<div>\n  </div>\n<div>\n <div>\n Part 2: Safety and efficacy trial in infants (5-12M inclusive) living in an area of high malaria transmission</div>\n <ul>\n <li>\n Primary Objective 1: Safety, Tolerability and Immunogenicity in infants (5-12M inclusive)\n <ul>\n <li>\n Measure the safety, tolerability and immunogenicity of the highest safe and well tolerated dose 666 of PfSPZ Vaccine administered by DVI in 3 or 4 doses to infants 5-12M inclusive of age. Dosage will be determined during the age de-escalation and dose escalation trial (Part 1) based on safety and tolerability.</li>\n </ul>\n </li>\n <li>\n Primary Objective 2: Efficacy in infants (5-12M inclusive)\n <ul>\n <li>\n Determine whether PfSPZ Vaccine administered by DVI to infants 5-12M inclusive of age at the highest safe and well tolerated dose of PfSPZ vaccine provides high-level (point estimate > 60%) protection against naturally acquired Pf infection, measured by blood smear microscopy, during 6 months following the last vaccine dose when compared to a control (placebo) group.</li>\n </ul>\n </li>\n </ul>\n <div>\n <strong>Secondary Objectives:</strong></div>\n <ul>\n <li>\n Secondary Objective 1: Determine safety and efficacy of alternative dosages of PfSPZ Vaccine at 6676 months after last vaccination</li>\n <li>\n Secondary Objective 2: Determine safety and efficacy of each dosage of PfSPZ Vaccine at 12 678 months after last vaccination</li>\n <li>\n Secondary Objective 3: Determine whether PfSPZ Vaccine administered by DVI to infants 5-12M 680 inclusive of age at any of the given doses of PfSPZ Vaccine provides high-level (point estimate > 60%) protection against naturally acquired Pf infection, measured by PCR, during 6 and 12 months following the last vaccine dose when compared to a control (placebo) group.</li>\n <li>\n Secondary Objective 4: Assess the cellular immunity and antibody responses induced by PfSPZ Vaccine</li>\n <li>\n Secondary Objective 5: Determine whether measured immune responses correlate with protection against Pf infection</li>\n <li>\n Secondary Objective 6: Determine the safety, tolerability, efficacy and immunological response provided by the addition of a booster dose 12 months after the primary vaccination series in infants 5M-12M of age on enrolment (dependent on achieving a statistically significant point estimate of at least 60% VE during 6 months follow-up)</li>\n </ul>\n <p>\n <strong>Exploratory Objectives</strong></p>\n <ul>\n <li>\n Objective 1: Determine the efficacy of PfSPZ Vaccine against Pf infection at specific parasite density thresholds (Pf parasite density >400 or >5000 parasites per microliter)</li>\n <li>\n Exploratory Objective 2: Determine the efficacy of PfSPZ Vaccine against malaria hospitalization (defined as hospitalization and Pf parasite density >5000 parasites per microliter or hemoglobin <5g/dl determined to be caused by malaria).</li>\n <li>\n Exploratory Objective 3: Determine whether any of the PfSPZ vaccination schedules has an effect on the prevalence of anemia as measured during the month 6 and month 12 visits</li>\n <li>\n Exploratory Objective 4: Measure allele-specific efficacy and selection of vaccine-resistant Pf genotypes through a genome-wide sieve analysis.</li>\n </ul>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<ul>\n <li>\n Healthy children 5 months – 12 years (Part 1) and healthy infants 5 -12M inclusive (Part 2) </li>\n <li>\n HIV negative </li>\n <li>\n Able to participate for the duration of the study. </li>\n <li>\n Parents/guardians over the age of 18 years able and willing to provide informed consent/permission. The consent/permission will be in writing.  For adult parents or guardians who are illiterate, an impartial witness can sign the consent/permission form on behalf of the parent and the parent/guardian will provide a thumbprint</li>\n</ul>\n<div>\n  </div>\n
      • principal_exclusion_criteria<ul>\n <li>\n Positive HIV test or breastfeeding infants or children of a known HIV positive mother (per Kenyan guidelines, these HIV exposed breastfeeding children should be on cotrimoxazole)</li>\n <li>\n Refusal of HIV testing</li>\n <li>\n Elevated ALT (liver function test) ≥2x ULN ( ALT >84 U/L)  </li>\n <li>\n Abnormal hematological parameters defined as: hemoglobin < 8 g/dl, WBC <1500 / mm3, neutrophils <750/ mm3, platelet count <75.000/ mm3</li>\n <li>\n Abnormal renal function test with creatinine >0.9 mg/dL</li>\n <li>\n Known sickle cell disease</li>\n <li>\n Current use of systemic immunosuppressant pharmacotherapy</li>\n <li>\n Current significant medical condition (cardiac, hepatic, renal, or hematological) or evidence of any other serious underlying medical condition identified by medical history, physical examination, or laboratory examination</li>\n <li>\n History of a splenectomy</li>\n <li>\n History of neurologic disorder (including seizures, other than uncomplicated febrile seizures)</li>\n <li>\n Known allergy to any component of the vaccine formulation, history of anaphylactic response to mosquito-bites, or known allergy to first or second line anti-malarials used to treat malaria</li>\n <li>\n Plan to participate in another investigational vaccine/drug research during or within 1 month of this study end</li>\n <li>\n Prior participation in a malaria vaccine trial</li>\n <li>\n Participation in the PfSPZ Vaccine Trial Part 1 (for Part 2 only)</li>\n <li>\n History of any other illness or condition which, in the investigator's judgment, may substantially increase the risk associated with the subject’s participation in the protocol or compromise the scientific objectives</li>\n <li>\n Child/orphan in institutional care</li>\n</ul>\n<div>\n  </div>\n
      • primary_end_points<p>\n Incidence of Pf parasitemia with parasite density >0 by thick blood smear</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n The study will be conducted at Siaya County Referral Hospital and Wagai Dispensary. </p>\n<p>\n Staff will include a study pediatrician and PI, a study site coordinator, a regulatory officer, administrative officer, data manager and data clerk, part time statistical support, sufficient clinical staff, including medical officers, clinical officers, nurses, quality assurance officers, community workers, laboratory personnel, including part time laboratory supervisor, and laboratory technicians and technologists, a pharmacist and pharmacist technician.  </p>\n<p>\n PI - Dr Martina Oneko, MD,Pediatrician</p>\n<p>\n PI - Dr Mary Hamel, MD</p>\n<p>\n Study Site Coordinator - Reuben Yego</p>\n<p>\n Pharmacist - Dr Tony Sang, BPharm</p>\n<p>\n Laboratory supervisor - Kephas Otieno, MSc</p>\n<p>\n Administrative officer - Diana Okello, MBA</p>\n<p>\n Data Manager - Wycliffe Odongo</p>\n<p>\n Data clerks</p>\n<p>\n Medical officer - To be hired</p>\n<p>\n Clinical officers</p>\n<p>\n Nurses</p>\n<p>\n Quality Assurance officers</p>\n<p>\n Community workers</p>\n<p>\n Laboratory personnel</p>\n<p>\n Laboratory technicians and technologists</p>\n<p>\n pharmacist technologist</p>\n<p>\n The trial budget also includes sufficient clinical supplies to test for malaria and provide treatment for common childhood diseases in the outpatient setting, ITNs for enrolled children, laboratory supplies for laboratory procedures, including immunological and molecular studies, transport costs, transport reimbursement for enrolled children.  </p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The proposed PfSPZ Vaccine has shown to be very safe and well tolerated in subjects in the US and Africa. High -level protective efficacy has been demonstrated in malaria naïve adult individuals, and therefore should be evaluated in African infants in an area of intense malaria transmission who continue to experience the highest morbidity and mortality from malaria and have not been exposed to frequent malaria infections.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n KEMRI Scientific Ethics Review Unit approved the trial on 27-Oct-2015</p>\n<p>\n CDC IRB approved the trial on 10-Nov-2015</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration3 years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorNormal saline placebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • 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 sites anticipated in Kenya.
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_siteWe will have only one site in Kenya
      • total_participants_worldwide536 participants
      • 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_healthyYes
      • 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_specifywe will enroll children below 12 years. Parental consent will be sought
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameMartina
      • investigator1_middle_name
      • investigator1_family_nameOneko
      • investigator1_qualificationMD, Pediatrician
      • investigator1_professional_addressKEMRI Center for Global Health Research, P.O.Box 1578-40100, Kisumu, Kenya
      • investigator1_telephone+254 717 747279
      • investigator1_emailmoneko@kemricdc.org
      • organisations_transferred_No
      • number_participants120 participants for the age de-escalation component of the study\n416 participants for the main study
      • notification
      • approval_date18-05-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted15-12-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<div style=\"margin-left: 28.35pt;\">\n <p style=\"margin-left: 0.3in;\">\n <strong>Safety, Tolerability and Efficacy of PfSPZ Vaccine Administered by Direct Venous Inoculation (DVI) to Healthy Children and Infants 5 Months through 9 Years of Age Living in an Area of High Malaria Transmission in Western Kenya</strong></p>\n <p>\n <strong>Leadership/Partnership:</strong></p>\n</div>\n<ul>\n <li>\n <strong>Kenya: </strong>Dr. Martina Oneko (site Principal Investigator)</li>\n <li>\n <strong>LSTM: </strong>Prof. Feiko ter Kuile (co-Investigator)</li>\n <li>\n <strong>CDC contact person:</strong> Dr. Laura Steinhardt (Co Principal Investigator), Dr Aaron Samuels (CDC-Kenya)</li>\n</ul>\n<p style=\"margin-left: 0.35in;\">\n <strong>Brief background</strong></p>\n<p>\n Double blind, randomized placebo controlled trial of PfSPZ Vaccine, consisting of cryopreserved, radiation-attenuated Plasmodium falciparum (Pf) sporozoites, which when given by direct venous inoculation showed dose-dependent, high level protection against controlled human malaria infection. The trial is divided into Part 1 – age de-escalation and dose escalation involving children between 5 months and 9 years inclusive, and Part 2, a 4-arm placebo controlled safety and efficacy trial in infants 5 to 12 months of age.</p>\n<p style=\"margin-left: 0.35in;\">\n <strong>Progress report</strong></p>\n<p>\n <strong>Overall Primary objective: </strong>Evaluate the safety, tolerability, immunogenicity and efficacy of PfSPZ Vaccine in infants in a high-transmission malaria setting in western Kenya by: 1) conducting and completing placebo controlled age de-escalation and dose escalation phase 2 trial in children and infants of 5 months through 9 years of age inclusive to evaluate safety and tolerability of increasing vaccine doses and to determine the safe doses to be used in the Part 2 safety and efficacy trial in infants; and 2) conducting and completing a placebo-controlled phase 2 trial to evaluate the safety, tolerability, immunogenicity, and efficacy against <em>Plasmodium falciparum </em>(Pf) infection of the three highest doses found to be safe in Part 1</p>\n<p>\n <strong>Primary Objective Part 1: </strong><em>Age de-escalation and dose escalation trial in children and infants (5 months – 9 years): </em>Measure the safety, tolerability and immunogenicity of PfSPZ Vaccine administered at escalating dosages by DVI in older children aged 5–9 years (highest three doses only), younger children aged 13–59 months, and infants 5–12M (at vaccination) at doses of 1.35x10⁵, 2.7x10⁵, 4.5x10⁵, 9.0x10⁵ and 1.8 x 10⁶ PfSPZ Vaccine given as a single dose or, for the two highest doses in two doses at 8 week intervals.</p>\n<ol style=\"list-style-type: lower-alpha;\">\n <li>\n <strong>Status</strong>: Data collection and analysis have been concluded. The CSR report is being finalized by the sponsor Sanaria.</li>\n <li>\n <strong>Major findings/accomplishments</strong>:</li>\n</ol>\n<p style=\"margin-left: 17.85pt;\">\n Find below the findings of Part 1 unblinded.</p>\n<p style=\"margin-left: 17.85pt;\">\n <u>Recruitment: </u>Study start was on 4 July, 2016, recruitment ended in November 2016.</p>\n<p style=\"margin-left: 17.85pt;\">\n Total number of consented participants: 282</p>\n<p style=\"margin-left: 17.85pt;\">\n Total number of enrolled participants:  165</p>\n<p style=\"margin-left: 17.85pt;\">\n Total number of screening failures: 117 participants</p>\n<p style=\"margin-left: 17.85pt;\">\n <u>Vaccinations: </u>156 participants, the target sample size, were successfully vaccinated with either 1 or 2 doses of the PfSPZ Vaccine, according to the dosing schedule. An additional 9 participants received an incomplete intravenous vaccination and were subsequently replaced, but followed up for safety. The last vaccination took place on 13 January 2017.</p>\n<p style=\"margin-left: 17.85pt;\">\n <u>Safety: </u>There were no Grade 3 related adverse events (AEs), laboratory abnormalities, or significant electrocardiogram changes post vaccination. Among participants of all ages, 26.8% of vaccine recipients and 35.8% of placebo recipients experienced a solicited AE that was considered related within seven days of immunization. Related systemic AEs were less common in vaccine recipients (10 of 112, or 8.9%) compared to placebo recipients (8 of 53, or 15.1%), solicited local symptoms at the injection site, primarily mild pain and swelling, occurred in 20.5% of vaccine recipients and 22.6% of placebo recipients. There was no obvious dose or age relationship.  Unsolicited AEs in the 28-day period following each vaccination deemed to be possibly or probably related occurred in nine of 112 (8.0%) vaccine recipients and 1 placebo recipient (1.9%); all were mild, resolved, and occurred within 7 days of vaccine/placebo injection. Three serious AEs were related to incident malaria infection. One severe malarial anemia occurred in a child 44 days after receiving her first dose of 9.0x10⁵ PfSPZ and two children in the 13–59-month-old group, both of whom had received one dose of 1.8x10⁶ PfSPZ Vaccine, experienced simple febrile seizures associated with malaria, one 26 days and the other 4 days after vaccination. One 8-year-old boy who received one injection of normal saline placebo developed an abscess on his finger after a capillary blood draw on vaccination day that was therefore considered related to a study procedure but not the study product. All grade 3 events resolved.</p>\n<p style=\"margin-left: 17.85pt;\">\n We had 4 DSMB (Data Safety and Monitoring Board) meetings, the last two on 05 December 2016 and  on 06 March 2017. On 05 December 2016 it was concluded that there were no safety concerns regarding the use of 4.5x10⁵, 9.0x10⁵ and 1.8 x 10⁶ doses of PfSPZ Vaccine in infants and that Part 2 of the study could start with these doses. On 06 March 2017 the results of second vaccinations at the 2 highest doses in infants were reviewed. As there were no safety concerns, we were allowed to continue Part 2 vaccinations, proceeding to vaccination 2 and later to vaccination 3, in the infants.</p>\n<ol style=\"list-style-type: lower-alpha;\">\n <li value=\"3\">\n <strong>Significance of those findings/accomplishments</strong>:</li>\n</ol>\n<p style=\"margin-left: 0.25in;\">\n Conclusion of Part 1 of the trial resulted in proof of safety and tolerability of PfSPZ Vaccine in the protocol specified dose ranges in infants, which allowed us to proceed into the efficacy trial in infants (Part 2).</p>\n<ol style=\"list-style-type: lower-alpha;\">\n <li value=\"4\">\n <strong>Challenges and lessons learned</strong>:</li>\n</ol>\n<ol>\n <li>\n Study start was delayed by about 3 months due to a delay in getting approval from the regulatory authorities and a clinical hold imposed on the sponsor by the FDA in the US.</li>\n</ol>\n<p style=\"margin-left: 0.5in;\">\n We expected about a rate of 25% screening failures and the final screening failure rate was 41%. About 30% of the screening failures were due to consent withdrawals by fathers before vaccination, and in most cases even before screening. The mothers had consented but when they reached home with the consent, fathers did not want their children to participate in the study, mostly because of the associated blood draws.</p>\n<p>\n <strong>Primary objectives Part 2</strong>:  <em>Safety and efficacy trial in infants (5-12M inclusive) living in an area of high malaria transmission: </em>1. Measure the safety, tolerability and immunogenicity of the highest safe and well tolerated dose of PfSPZ Vaccine administered by DVI in 3 doses to infants 5-12M inclusive of age.  Dosage has been determined to be 4.5x10⁵, 9.0x10⁵ and 1.8 x 10⁶ PfSPZ Vaccine during the age de-escalation and dose escalation trial (Part 1) based on safety and tolerability. 2. Determine whether PfSPZ Vaccine administered by DVI to infants 5-12M inclusive of age at a pre-specified well tolerated dose level provides high-level (point estimate <u>></u> 60%) protection against naturally acquired Pf infection, measured by blood smear microscopy, during 6 months following the last vaccine dose when compared to a control (placebo) group. </p>\n<ol style=\"list-style-type: lower-alpha;\">\n <li>\n <strong>Status: </strong> All primary vaccinations have been given as of 15 AUG2017. Twelve months of follow up for safety, immunogenicity and efficacy have been completed for all participants on 15AUG2018. Data lock occurred on 15OCT2018. Data analysis is ongoing. PCR assays to detect malaria are still ongoing at the KEMRI/CDC laboratories in Kisumu. Specific antibody assays and cell assays for assessment of parasite-specific T cell responses are ongoing at laboratories of our collaborators in the United States. Epstein Barr Virus serological assays are ongoing at the University of Massachusetts. Parasite genotyping is ongoing at the University of Maryland.</li>\n <li>\n <strong>Major findings/accomplishments:</strong></li>\n</ol>\n<p style=\"margin-left: 0.25in;\">\n <u>Recruitment:</u> In December 2016, multiple meetings with members of the communities in Siaya and Wagai (our satellite study clinic) took place. We concentrated on the issues we had encountered during Part 1 of the study and explained the blood draws and the vaccination procedure in detail. Study start for part 2 was on 03 January 2017. Consenting of the last participant took place on 10APR2017, and a total of 548 parents of potential participants were consented. Of these, 212 (38.7%) are confirmed screening failures. A total of 337 participants were enrolled and randomized, although one mother withdrew consent after randomization, leaving 336 participants who were vaccinated.</p>\n<p style=\"margin-left: 0.25in;\">\n <u>Vaccinations:</u>  Vaccinations in part 2 started on 23JAN2017, and the last enrolment (i.e. the last vaccination 1) took place on 13 April 2017.  The last vaccination 3 was given on 15AUG2017.</p>\n<p style=\"margin-left: 0.25in;\">\n <u>Safety:</u> Final unblinded safety evaluations showed no related serious adverse events; unrelated serious adverse events occurred in 38/252 (15.1%) of vaccine participants and in 8/84 (9.5%) of those who had received placebo. One child (placebo recipient) died at home due to bee attack. Grade 3 unsolicited adverse events included simple febrile seizures, considered to be adverse events of special interest which did not fulfil SAE criteria and were reported throughout the study period; at least one febrile seizure was reported in 14/252 (5.6%) of vaccinees compared to 4/84 (4.8%) of placebo recipients. Unsolicited adverse events which were considered possibly or probably related occurred in 15/252 (6%) of vaccine recipients compared to 4/84 (4.8%) of placebo recipients; all were of mild severity. Solicited local adverse events occurred in 11.9% of vaccine recipients and in 16.7% of placebo recipients after a total of 980 vaccinations: 2 participants(0.6%) one a vaccine recipient and the other a placebo recipient had severe swelling at the injection site, and one of those was withdrawn from further vaccination. There was a clear trend that injection site swelling was less common at vaccinations 2 and 3. Overall, 45.6% of vaccine recipients and 45.2% of placebo recipients experienced solicited systemic adverse events like fever, drowsiness, irritability or loss of appetite during the first week post vaccination, but most of these were related to other infections and thus unlikely related to the vaccine. Possibly and probably related solicited systemic reactions were observed in 24/252 (9.5%) of vaccine recipients and in 7/84 (8.3%) of placebo recipients after a total of 980 vaccinations, with one Grade 3 reaction in the placebo group (one spike of fever to 40.1 ⁰Celsius) which was considered possibly related in the absence of another explanation. There was no trend showing that solicited systemic events increased after second or third doses.</p>\n<p style=\"margin-left: 0.25in;\">\n <u>Feasibility:</u> In a total of 980 injections, 95.2% were successful with one needle stick. Children did not cry during 15.8% of injections with vaccine versus 18.2% of injections with placebo.</p>\n<p style=\"margin-left: 0.25in;\">\n <u>Efficacy: </u> The 6 month endpoint of vaccine efficacy (VE) by proportional analysis was 12% by proportional  analysis and 30.1% by survival analysis method in infants who had received 3 doses of 18 x 10⁵PfSPZ. In the 9.0 x 10⁵ PfSPZ group VE was -6.5% by proportional analysis and 3.3% by survival analysis, and in the 4.5 x 10⁵ PfSPZ group proportional analysis showed VE of 0.8% and survival analysis of 13.5%. None of these results were statistically significant. Thus the efficacy needed per protocol to allow for a booster dose was not reached.</p>\n<p style=\"margin-left: 0.25in;\">\n <u>Immunogenicity: </u>The vaccine was immunogenic in all 3 dose groups in terms of circumsporozoite antibody titers 2 weeks after vaccination 3. Those who did not become infected had significantly higher response to PfCSP in the 18x10⁵ and 4.5x10⁵ PfSPZ groups</p>\n<ol style=\"list-style-type: lower-alpha;\">\n <li value=\"3\">\n <strong>Significance of those findings/accomplishments:</strong></li>\n</ol>\n<p style=\"margin-left: 0.25in;\">\n Feasibility of intravenous inoculation by DVI in infants was assessed during all vaccinations. In total, several very experienced injectors managed to vaccinate 95.2% of the infants in Part 2 by 1 direct venous inoculation. This is an improvement compared to Part 1, where only 75% of the infants were vaccinated by 1 single injection. The injector performance improved significantly over time and this finding is important also for other future vaccinations which have to be given to infants via the intravenous route. </p>\n<p style=\"margin-left: 0.25in;\">\n The vaccine was overall safe and well tolerated, but the efficacy did not reach the expected levels while circumsporozoite antibody titers were increased in all dose groups 2 weeks after vaccination 3. Further immunological evaluation and parasite genotyping may provide the answer why the vaccination in infants did not show the same levels of efficacy as in malaria naïve adults. </p>\n<ol style=\"list-style-type: lower-alpha;\">\n <li value=\"4\">\n <strong>Challenges and lessons learned</strong>:</li>\n</ol>\n<p style=\"margin-left: 0.25in;\">\n Recruitment of participants was a challenge. Consent withdrawals before screening contributed in about 50% to the screening failures, mostly by fathers.  The original sample size of 416 participants was not reached, but the previously expected minimum number of 320 participants was exceeded and we enrolled 336 participants. 98.2% of the scheduled follow up visits were completed. We retained 303 children in the study, however only 260 participants remained in the ATP cohort, falling short of our original aim to retain 280 children in the ATP cohort.  46 participants have dropped out of the study for various reasons, including consent withdrawals (14) and migration out of the study area (26).</p>\n<div>\n  </div>\n
      • implication_results
      • quantity_imported136 Vials(450,000 PfSPZ/vial) + 2290 vials(150,000 PfSPZ/vial)
      • quantity_dispensed63 Vials(150,000 PfSPZ/vial) + 2123 vials(450,000 PfSPZ/vial)
      • quantity_destroyedNone
      • quantity_exported73 Vials(150,000 PfSPZ/vial) + 240 vials(450,000 PfSPZ/vial)
      • balance_siteNone
      • final_date0000-00-00
      • modified2025-01-28 11:57:45
      • created2015-10-22 10:52:37
      • total_sites(null)
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    • InvestigatorContact(array)
      • 0(array)
        • id291
        • application_id436
        • given_nameMartina
        • middle_name
        • family_nameOneko
        • qualificationMD
        • professional_addressKEMRI Center for Global Health Research, P.O.Box 1578-40100, Kisumu, Kenya
        • telephone+254 717 747279
        • emailmoneko@kemricdc.org
        • created2015-10-22 10:58:47
        • modified2020-12-15 14:25:12
      • 1(array)
        • id292
        • application_id436
        • given_nameMary
        • middle_nameJ
        • family_nameHamel
        • qualificationMD
        • professional_addressCenters for Disease Control and Prevention, Atlanta, GA, USA
        • telephone+ 1 404 3886811
        • emailmlh8@cdc.gov
        • created2015-10-22 11:05:01
        • modified2020-12-15 14:25:12
    • SiteDetail(array)
      • 0(array)
        • id349
        • application_id436
        • county_id41
        • site_nameSiaya County Referral Hospital
        • physical_addressSiaya Town
        • contact_details+254 717 747279
        • contact_personDr Martina Oneko
        • site_capacity(null)
        • misc(null)
        • created2015-10-22 10:58:47
        • modified2020-12-15 14:25:12
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 1(array)
        • id358
        • application_id436
        • county_id41
        • site_nameWagai Health Center
        • physical_addressWagai Market
        • contact_details+254 717 747279
        • contact_personDr Martina Oneko
        • site_capacity(null)
        • misc(null)
        • created2015-11-06 11:39:05
        • modified2020-12-15 14:25:12
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id227
        • application_id436
        • sponsorSanaria
        • sponsor_typeIndustry
        • contact_personStephen L. Hoffman
        • address9800 Medical Center Dr A209, Rockville, MD 20850, United States
        • telephone_number+1 301-770-3222
        • fax_number
        • cell_number+1 301-770-3222
        • email_addresssanaria@sanaria.com
        • created2015-10-22 10:58:47
        • modified2020-12-15 14:25:12
  • 1(array)
    • Application(array)
      • id452
      • user_id311
      • trial_status_id5
      • abstract_of_study<div>\n <h1>\n ABSTRACT </h1>\n</div>\n<p style=\"margin-left:.5in;\">\n <strong>Background</strong></p>\n<p style=\"margin-left:.5in;\">\n Spinal anesthesia is an effective regional anesthesia technique, which is preferred in almost 86% of cesarean sections in the United States and United Kingdom. At least 80% of cesarean sections done at the Aga Khan University hospital are under spinal anesthesia. Shivering is a common complication of spinal anesthesia; it occurs in 40%-64% of patients after neuraxial anesthesia. Shivering may cause maternal and fetal hypoxemia, maternal discomfort and a problem to the anesthesiologists when it comes to monitoring the patient during cesarean sections.</p>\n<p style=\"margin-left:.5in;\">\n Ondansetron a 5ht3 receptor antagonist is effective in treatment and prevention of post anesthesia shivering. In published studies use of fixed dose in patients with different weights in the various groups, masked the dose effect ondansetron in preventing shivering. Such that not adjusting the dose according to the weight of patients in the sample group resulted in a higher occurrence of shivering. No study compares different doses of ondansetron in preventing shivering in parturient women who have had spinal anesthesia for cesarean section.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p style=\"margin-left:.5in;\">\n <strong>Objectives: </strong>To determine if a weight-adjusted dose is better than a fixed dose of ondansetron in preventing shivering following spinal anesthesia for cesarean delivery<strong>.</strong></p>\n<p style=\"margin-left:.5in;\">\n <strong>Study design</strong><strong>:  </strong></p>\n<p style=\"margin-left:.5in;\">\n Double blinded Randomized Controlled Trial</p>\n<p style=\"margin-left:.5in;\">\n <strong>Method</strong>: This is a randomized, double-blinded controlled trial of 124 women scheduled for elective cesarean surgery. The Women will be allocated into two equal groups. The intervention group will receive intravenous ondansetron weight adjusted dosing at 0.1mg/kg and control group will get a fixed dose of 4mg before spinal anesthesia. The occurrence and severity of shivering and other outcomes, such as headache, pruritus will be assessed and recorded during the surgery and postoperative period.</p>\n<p style=\"margin-left:.5in;\">\n Data will be collected using questionnaires.Data analysis undertaken using the SPSS version 15. Chi-square tests, will be used to compare incidence of shivering between the two groups. To compare severity of shivering between the groups, the Wilcoxon sum rank test will be used. A significance level of 0.05 will be used for all hypothesis test.</p>\n<p style=\"margin-left:.5in;\">\n  </p>\n
      • study_title<p>\n <strong>COMPARISON OF WEIGHT ADJUSTED DOSE VERSUS FIXED DOSE ONDANSETRON IN PREVENTING SHIVERING FOLLOWING SPINAL ANESTHESIA FOR CESAREAN DELIVERIES. </strong></p>\n
      • laymans_summary(null)
      • short_titlecomparison of weight adjusted versus fixed dose ondansetron in preventing shivering following spinal anesthesia for cesarean deliveries
      • protocol_noECCT/16/02/04
      • version_no2015/REC-14(V2)
      • date_of_protocol11-08-2014
      • study_drugondansetron
      • disease_conditionshivering after spinal anesthesia
      • 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_nameondansetron
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressdrmokigi@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
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      • 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)
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      • applicant_hard_copies(null)
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      • declaration_applicantMOSES KIMURI GICHERU P.O.BOX 30270 (00100) GPO NAIROBI KENYA
      • declaration_date115-02-2016
      • declaration_principal_investigatorPROF VITALIS MUNGAYI P.O.BOX 30270 (00100) GPO NAIROBI KENYA
      • declaration_date215-02-2016
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<h2>\n <strong>ELIGIBILITY CRITERIA</strong></h2>\n<p style=\"margin-left:32.0pt;\">\n All ASA 1 and 2 healthy patients over 18 years scheduled for cesarean deliveries under spinal anesthesia.</p>\n
      • principal_exclusion_criteria<h2>\n <strong>EXCLUTION CRITERIA</strong></h2>\n<p style=\"margin-left:.5in;\">\n Pre-operative use of ondansetron, tramadol, pethidine, clonidine. This drugs have been used in the prevention and treatment of shivering.</p>\n<p style=\"margin-left:.5in;\">\n Allergy or intolerance to ondansetron.</p>\n<p style=\"margin-left:.5in;\">\n Presence of shivering before drug administration.</p>\n
      • primary_end_points<p>\n To compare the effectiveness of a weight adjusted dose and a fixed dose in preventing shivering, post spinal anesthesia for cesarean sections.</p>\n<p>\n Compare the grade of shivering between the groups. Occurrence of Pruritus and headache between the two group</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • 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_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n This study will be carried out at agakhan unversity hospital,</p>\n<p>\n <strong>SUPERVISORS</strong></p>\n<p>\n  </p>\n<p>\n <strong>Dr. VITALIS MUNG'AYI</strong></p>\n<p>\n MB ChB, MMED Anesthesia (Nairobi), FICM (South Africa),</p>\n<p>\n Asst. Professor, Department of Anesthesia,</p>\n<p>\n Aga Khan University, East Africa</p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n <strong>Dr. SAMINAR MIR</strong></p>\n<p>\n MBBS, MMED Anesthesia (Nairobi), Certificate obstetric Anesthesia (Israel)</p>\n<p>\n Consultant Anesthetist<strong>,</strong> senior instructor, Department of Anesthesia</p>\n<p>\n Aga Khan University,</p>\n<p>\n  </p>\n<p>\n <strong>DR. JIMMY KABUGI</strong></p>\n<p>\n MB ChB, MMED Anesthesia (Nairobi), Fellow cardiac anesthesia.</p>\n<p>\n Consultant Cardiac Anesthetist, Program director department of anesthesia.</p>\n<p>\n Aga Khan University, East Africa.</p>\n
      • other_details_explanation
      • other_details_regulatory_notapproved<p>\n PAN AFRICAN CLINICAL TRIAL REGISTRY APPIED ON 2/15/2016</p>\n
      • other_details_regulatory_approved<p>\n AGA KHAN UNIVERSTY, NAIROBI HEALTH RESEARCH ETHICS COMMITTEE APPROVED ON 10/08/2015</p>\n
      • other_details_regulatory_rejected
      • other_details_regulatory_halted
      • estimated_durationONE YEAR
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorweight adjusted dose vers
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaAGA kHAN UNIVERSITY HOSPITAL
      • single_site_physical_address3RD PARKLANDS NAIROBI
      • single_site_contact_personMOSES KIMURI GICHERU
      • single_site_telephone0723742091
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeNo
      • total_enrolment_per_siteONE HUNDRED AND TWENTY FOUR
      • total_participants_worldwideONE HUNDRED AND TWENTY FOUR
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenYes
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameprof mungayi
      • investigator1_middle_namevitalis
      • investigator1_family_namemungayi
      • investigator1_qualificationanesthesiologis
      • investigator1_professional_addressmungayi@gmail.com, 3rd Parklands Avenue P.O. Box 30270 GPO 00100, Nairobi, Kenya
      • investigator1_telephone+254 733 635554
      • investigator1_emailmungayi@gmail.com
      • organisations_transferred_No
      • number_participantsone hundred and twenty four
      • notification
      • approval_date11-03-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted15-02-2016
      • 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)
      • modified2016-10-10 15:03:59
      • created2015-11-23 10:09:41
      • total_sites(null)
      • ecitizen_invoice(null)
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        • application_id452
        • given_namemoses kimuri gicheru
        • middle_nameKIMURI
        • family_namegicheru
        • qualificationanesthesiology resident
        • professional_address3rd Parklands Avenue P.O. Box 30270 GPO 00100, Nairobi, Kenya
        • telephoneo723742091
        • emaildrmokigi@gmail.com
        • created2015-11-23 10:32:27
        • modified2016-02-15 08:34:00
    • SiteDetail(array)
      • 0(array)
        • id361
        • application_id452
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2015-11-23 10:32:27
        • modified2016-02-15 08:34:00
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id235
        • application_id452
        • sponsorAGA KHAN UNIVERSITY
        • sponsor_type(null)
        • contact_personKAMANDA CIRU
        • address3rd Parklands Avenue P.O. Box 30270 GPO 00100, Nairobi, Kenya
        • telephone_number0203662148
        • fax_number
        • cell_number0203662148
        • email_addressKAMANDA.CIRU@AKU.EDU
        • created2015-11-23 10:32:27
        • modified2016-02-15 08:34:00
  • 2(array)
    • Application(array)
      • id472
      • user_id310
      • trial_status_id(null)
      • abstract_of_study<p>\n <strong>ABSTRACT </strong></p>\n<p>\n <strong>Background </strong></p>\n<p>\n The use of pharmacological agents to attenuate the haemodynamic response to laryngoscopy and endotracheal intubation is the standard of care for elective surgery in most institutions worldwide. Current evidence is conflicting concerning the best agent and optimal dose for this purpose. Fentanyl is widely utilized to attenuate haemodynamic compromise. Ketamine, a widely available drug, has been scarcely studied in this regard at low doses and against varying doses of other common agents.</p>\n<p>\n <strong>Objective</strong></p>\n<p>\n The primary objective is to compare the overall incidence of hypertension and tachycardia immediately pre-intubation (post-induction) until 10 minutes post intubation between the study group receiving fentanyl at 1.0 mcg/kg and the group receiving Ketamine at 0.5 mg/kg.</p>\n<p>\n The secondary objectives are to compare the incidence of pre-laryngoscopy/intubation hypotension and of neuropsychiatric phenomena on emergence between the two groups.</p>\n<p>\n <strong>Primary outcome measure</strong><strong>:</strong> Increase of SBP of more than</p>\n<p>\n 20% from the baseline.</p>\n<p>\n <strong>Study Setting:</strong> The Aga Khan University Hospital, Nairobi</p>\n<p>\n <strong>Study Design</strong>:  A prospective, double blind, superiority, randomized control trial.</p>\n<p>\n <strong>Sample size:   </strong>A sample size of 88 participants, 44 in each arm.</p>\n<p>\n <strong>Study population</strong><strong>:</strong>  ASA I and II patients aged 18-65 years scheduled for theatre for non-emergent surgery</p>\n<p>\n <strong>Anaesthetic Procedure:</strong></p>\n<p>\n 88 adult patients will be randomly assigned to one of two groups corresponding to the agents applied for induction: (a) Fentanyl (1.0 µg/kg) added to Propofol (2.0 mg/kg) (F, n = 43) and (b) Ketamine (0.5 mg/kg) added to Propofol (2.0 mg/kg) (K, n = 43), and haemodynamic responses evaluated by determining heart rate and blood pressure immediately before laryngoscopy and at 2.5, 5, 7.5 and 10 min. This will be in addition to standard of care.</p>\n<p>\n  </p>\n<p>\n <strong>Data collection</strong></p>\n<p>\n Data will be collected using a data collection tool (see appendix).  Patients’ baseline characteristics, systolic blood pressure, mean arterial pressure, diastolic blood pressure and heart rate at baseline then at minute 1, 2.5, 5, 7.5 and 10 will be recorded.</p>\n<p>\n <strong>Data analysis</strong></p>\n<p>\n Data analysis will be undertaken using the SPSS version 15 with the input of a statistician. All data and results will be tabulated. P < 0.05 will be considered statistically significant for all data.</p>\n<p>\n Demographic characteristics will be expressed as the following: Age (years), Weight (kg) and Height (cm) as mean ± SD; Sex (male/female) and ASA Class (I/II) as a ratio; Neuropsychiatric phenomena on recovery [n(%)] as a percentage.</p>\n<p>\n A minimum 20% change in the continuous variables (heart rate, SBP. MAP and DBP) relative to the baseline between the groups will be considered significant. These variables will be expressed as appropriate measures of central tendency i.e. means ± SD (or medians if not normally distributed) then analysed statistically with student's unpaired t-test (means) and chi-square test (proportions). For non-parametric data the Mann-Whitney-Wilcoxon test will be used. Compound line graphs will be used to present these results.*</p>\n
      • study_title<p align=\"center\">\n <strong>EFFECT OF LOW-DOSE KETAMINE VERSUS FENTANYL ON ATTENUATING THE HAEMODYNAMIC RESPONSE TO LARYNGOSCOPY AND ENDOTRACHEAL INTUBATION IN PATIENTS UNDERGOING GENERAL ANAESTHESIA AT THE AGA KHAN UNIVERSITY HOSPITAL, NAIROBI</strong></p>\n
      • laymans_summary(null)
      • short_titleEFFECT OF LOW-DOSE KETAMINE VERSUS FENTANYL ON ATTENUATING THE HAEMODYNAMIC RESPONSE TO LARYNGOSCOPY AND ENDOTRACHEAL INTUBATION IN PATIENTS UNDERGOING GENERAL ANAESTHESIA
      • protocol_noECCT/16/02/03
      • version_no1
      • date_of_protocol05-11-2015
      • study_drugFentanyl, Ketamine
      • disease_conditionNot disease. Physiological response to laryngoscopy and endotracheal intubation
      • 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_nameFentanyl, Ketamine
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressangela.ongewe@aku.edu
      • 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_applicantAngela Ongewe
      • declaration_date122-01-2016
      • declaration_principal_investigatorAngela Ongewe
      • declaration_date222-01-2016
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<p style=\"margin-left:1.0in;\">\n ·         ASA I and II patients 18-65 years scheduled for non-emergent surgery.</p>\n
      • principal_exclusion_criteria<p style=\"margin-left:1.0in;\">\n ·         History of allergy or contraindications to any of the study drugs</p>\n<p style=\"margin-left:1.0in;\">\n ·         Patients scheduled for emergency surgery</p>\n<p style=\"margin-left:1.0in;\">\n ·         Hypertension – i.e. a known/previously diagnosed hypertensive as per the American Heart Association guidelines</p>\n<p style=\"margin-left:1.0in;\">\n ·         Pregnancy</p>\n<p style=\"margin-left:1.0in;\">\n ·         Known ischaemic heart disease</p>\n<p style=\"margin-left:1.0in;\">\n ·         Known raised intracranial pressure or intracranial pathology where a rise in intracranial pressure would pose a risk or patients scheduled for neurosurgical procedures</p>\n<p style=\"margin-left:1.0in;\">\n ·         History, indicator (Mallampati score) of or proven difficult ventilation/laryngoscopy/intubation</p>\n<p style=\"margin-left:1.0in;\">\n ·         Intubation time greater than 30 seconds</p>\n
      • primary_end_points<p>\n Increase of SBP/DBP/MAP/HR of more than 20% from the baseline </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic1
      • 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_other1
      • trial_other_specifyA superiority randomised controlled trial to compare the effect of low dose Ketamine with Fentanyl on attenuating the heamodynamic response to laryngoscopy and endotracheal intubation.
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <em><strong>Ref: www.aku.edu</strong></em></p>\n<p>\n  </p>\n<p>\n Attached are CVs of supervisors/study co-ordinators</p>\n<p>\n <span style=\"color: rgb(0, 0, 0); font-family: Arial; line-height: 18px;\">Aga Khan University Hospital, Nairobi provides comprehensive healthcare and support services of the highest international standard. There is an outstanding team of physicians and medical staff, state-of-the-art technologies, and modern facilities.</span></p>\n<p>\n Aga Khan Hospital has state of the art Operating Theatres, with up-to-date theatre equipment and highly qualified staff who provide 24-hour services. </p>\n<p class=\"ms-rteElement-P\" style=\"padding-right: 5px; font-family: Arial; margin-bottom: 18px !important; padding-left: 0px !important; font-stretch: normal !important; line-height: 18px !important;\">\n Aga Khan University Hospital, Nairobi provides world class accident and emergency services to patients from across the entire East and Central Africa region.</p>\n<p class=\"ms-rteElement-P\" style=\"padding-right: 5px; font-family: Arial; margin-bottom: 18px !important; padding-left: 0px !important; font-stretch: normal !important; line-height: 18px !important;\">\n Open 24 hours a day, our Accident and Emergency (A&E) Department ensures that each patient is initially assessed according to the Canadian Triage Acuity Scale (CTAS), which is a well recognized and validated triage system that prioritizes patient care by severity of illness. The dedicated team of doctors and nurses who staff our A&E Department are highly trained in accident and emergency medicine. AKUH,N also ensures that they are kept up-to-date with the most current knowledge and skills by actively supporting their continuing professional education.</p>\n<p class=\"ms-rteElement-P\" style=\"padding-right: 5px; font-family: Arial; margin-bottom: 18px !important; padding-left: 0px !important; font-stretch: normal !important; line-height: 18px !important;\">\n The A&E department is equipped with resuscitation bays for critically ill patients, procedure rooms for surgical emergencies, examination rooms equipped with piped oxygen and vacuum suction machines, and observation beds</p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n Nil</p>\n
      • other_details_regulatory_approved<p>\n Aga Khan University Hospital Nairobi Research Scientific and Ethics Committees.</p>\n<p>\n Date of Approval: 05.11.2015</p>\n<p>\n 1 site (the Aga Khan Universtiy Hospotal, Nairobi)</p>\n
      • other_details_regulatory_rejected<p>\n Nil</p>\n
      • other_details_regulatory_halted<p>\n Nil</p>\n
      • estimated_duration6 moths
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorFentanyl (versus Ketamine
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaAga Khan University Hospital, Nairobi
      • single_site_physical_address3rd Parklands Avenue, Nairobi
      • single_site_contact_personAngela Ongewe
      • single_site_telephone0723 624 595
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeNo
      • total_enrolment_per_site88
      • total_participants_worldwide88
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • 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_nameAngela
      • investigator1_middle_name
      • investigator1_family_nameOngewe
      • investigator1_qualificationMBChB (resident anaesthesiology)
      • investigator1_professional_addressP.O.Box 30270 - 00100 GPO Nairobi
      • investigator1_telephone0723 624 595
      • investigator1_emailangela.ongewe@gmail.com
      • organisations_transferred_No
      • number_participants88
      • notification
      • approval_date11-03-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted14-02-2016
      • 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)
      • modified2016-03-11 08:52:08
      • created2016-01-22 05:57:55
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id310
        • application_id472
        • given_nameAngela
        • middle_name
        • family_nameOngewe
        • qualificationMbCHb (resident anaesthesiology)
        • professional_addressP.O.BOx 30270 - 00100 GPO Nairobi
        • telephone0723 624 595
        • emailangela.ongewe@gmail.com
        • created2016-01-22 06:07:35
        • modified2016-02-14 16:37:36
    • SiteDetail(array)
      • 0(array)
        • id369
        • application_id472
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2016-01-22 06:07:35
        • modified2016-02-14 16:37:36
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id243
        • application_id472
        • sponsorAga Khan University Hospital
        • sponsor_type(null)
        • contact_person
        • address3rd Parklands Avenue. P.O.Box 30270-00100 GPO Nairobi
        • telephone_number+254 20 366 2263
        • fax_number
        • cell_number+254 711 09 2000
        • email_addressakuh.nairobi@aku.edu
        • created2016-01-22 06:07:35
        • modified2016-02-14 16:37:36
  • 3(array)
    • Application(array)
      • id477
      • user_id316
      • trial_status_id(null)
      • abstract_of_study<p>\n Acute respiratory infections (ARI) are a major cause of child morbidity and mortality globally. Pneumonia in particular is the leading cause of child mortality with developing countries accounting for majority of the deaths. In Kenya 17% of deaths among children below five years were caused by pneumonia. A total of 534,863 new cases of childhood pneumonia were registered in the year 2013 alone. The World Health Organization (WHO) recommends using respiratory rate cut-offs for diagnosis and classification of pneumonia in low-resource settings where chest radiology or blood tests are largely unavailable.  Accurate respiratory rate counting is thus critical in determining the subsequent management of childhood pneumonia. Therefore, it is crucial to improve ways of counting the respiratory rate. Having a better and more reliable device for accurate respiratory rate count is important for diagnosis and management of pneumonia in children. The Philips Research Group has developed an automated pneumonia diagnostic device named as “Children’s Automated Respiration Monitor (ChARM)”.The device automatically measures the respiratory rate and classifies according to the current WHO guidelines. This study aims at assessing the accuracy, usability and acceptability of the device as a step towards recommending it for large scale public use in the management of pneumonia in children.</p>\n
      • study_title<p>\n  </p>\n<p>\n  </p>\n<p>\n <strong>ASSESSING </strong><strong>THE ACCURACY, USABILITY AND ACCEPTABILITY OF CHILDREN’S AUTOMATED RESPIRATORY MONITOR AT SELECTED CLINICS IN  TURKANA COUNTY, KENYA ‘</strong></p>\n<p>\n <br />\n  </p>\n
      • laymans_summary(null)
      • short_titleASSESSING THE ACCURACY, USABILITY AND ACCEPTABILITY OF CHILDREN’S AUTOMATED RESPIRATORY MONITOR AT SELECTED CLINICS IN TURKANA COUNTY, KENYA ‘
      • protocol_noECCT/16/02/01
      • version_no7.0,
      • date_of_protocol10-12-2015
      • study_drugdevice for respiratory measurement
      • disease_conditionpneumonia
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device1
      • product_type_chemical_namenot applicable
      • product_type_medical_device_nameChild automated respiratory monitori
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressisaiahmwangi@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_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 ISAIAH MWANGI
      • declaration_date102-02-2016
      • declaration_principal_investigatorDR RASHID SHAH
      • declaration_date202-02-2016
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<ol>\n <li>\n Child <5 years of age who will be attending Lodwar county hospital, Turkana county in Kenya will be eligible for the accuracy aspect of the study.</li>\n <li>\n Parents/caregivers of a recruited child  stated above will be eligible for the acceptability aspect of the study</li>\n <li>\n Health care provider in the participating health facilities will be eligible for usability and quality of care aspects of the study.</li>\n</ol>\n
      • principal_exclusion_criteria<ol>\n <li>\n Child <5 years of age who will be attending Lodwar county hospital, Turkana county in Kenya will be eligible for the accuracy aspect of the study.</li>\n <li>\n Parents/caregivers of a recruited child  stated above will be eligible for the acceptability aspect of the study</li>\n <li>\n Health care provider in the participating health facilities will be eligible for usability and quality of care aspects of the study.</li>\n</ol>\n
      • primary_end_points<p>\n TOTAL RECRUITS REACH 120</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_specifyMEICAL DEVICE
      • trial_human_pharmacology1
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyDEVICE
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n RESEARCH ASSISTANT</p>\n<p>\n STUDY CO ORDINATOR</p>\n<p>\n LIAISON PERSON</p>\n
      • other_details_explanation<p>\n This device is meeant for poor resource countries and Kenya is one of them</p>\n
      • other_details_regulatory_notapproved<p>\n NONE</p>\n
      • other_details_regulatory_approved<p>\n SAVE THE CHILDREN,S FUND USA</p>\n
      • other_details_regulatory_rejected
      • other_details_regulatory_halted
      • estimated_duration3 MONTHS
      • 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_countriesNo
      • multiple_member_states
      • number_of_sites1
      • multi_country_list
      • data_monitoring_committeeNo
      • total_enrolment_per_site120
      • total_participants_worldwide120
      • 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_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_nameRASHID
      • investigator1_middle_name
      • investigator1_family_nameSHAH
      • investigator1_qualificationPHD
      • investigator1_professional_addressKENYA MEDICAL RESEARCH INSTITE
      • investigator1_telephone+1 443 683 6236
      • investigator1_emailmshah@savethechildren.org
      • organisations_transferred_Yes
      • number_participants120
      • notification
      • approval_date21-03-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted18-02-2016
      • 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)
      • modified2016-03-21 19:32:37
      • created2016-02-02 10:02:11
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id319
        • application_id477
        • given_nameISAIAH
        • middle_name
        • family_nameMWANGI
        • qualificationMSC
        • professional_addressKENYA MEDICAL RESEARCH INSTITUTE
        • telephone+ 254 724 568 332
        • emailisaiahmwangi@gmail.com
        • created2016-02-02 10:04:36
        • modified2016-02-18 17:05:15
    • SiteDetail(array)
      • 0(array)
        • id380
        • application_id477
        • county_id23
        • site_namelodwar hospital
        • physical_address po box 20 lodwar
        • contact_detailsTel 0703677168
        • contact_personDave EKWAM
        • site_capacity(null)
        • misc(null)
        • created2016-02-02 10:04:36
        • modified2016-02-18 17:05:15
        • County(array)
          • id23
          • county_nameTurkana
          • created2012-06-15 10:24:43
          • modified2012-06-15 10:24:43
    • Sponsor(array)
      • 0(array)
        • id252
        • application_id477
        • sponsorPHILIPS MEDICAL
        • sponsor_type(null)
        • contact_personPavan Evan
        • addressPHILIPS MEDICAL NETHERLANDS
        • telephone_number+ 41 278 443 9877
        • fax_number
        • cell_number+ 41 278 5569265
        • email_addressinfo@philipsmedical.com
        • created2016-02-02 10:04:36
        • modified2016-02-18 17:05:15
  • 4(array)
    • Application(array)
      • id424
      • user_id32
      • trial_status_id5
      • abstract_of_study<div>\n Background and rationale: Children hospitalised with severe anaemia in Africa are at high risk of readmission or death within 6 months after discharge. No strategy specifically addresses this post-discharge period. In Malawi, 3 months of post-discharge malaria chemoprevention (PMC) with monthly 3-day treatment courses of artemether-lumefantrine (AL) in children with severe malarial anaemia prevented 31% of deaths and readmissions. The effect was in addition to the effect of insecticide-treated bednets. These promising findings now need to be confirmed in other settings before the World Health Organisation can consider PMC for the post-discharge management of severe anaemia.</div>\n<div>\n  </div>\n<div>\n Primary efficacy objective: To determine if 3 months of post-discharge malaria chemoprevention with monthly 3-day treatment courses of dihydroartemisinin-piperaquine (DP) (PMC-DP) is safe and superior to the standard single 3-day treatment course with artemether-lumefantrine provided as part of standard in-hospital care in reducing all-cause readmissions and deaths by 6 months in the post-discharge management of children less than 5 years of age admitted with severe anaemia.</div>\n<div>\n  </div>\n<div>\n Hypothesis: An additional three months of malaria chemoprevention with monthly 3-day treatment courses with DHA-piperaquine (each providing about 4 weeks of post-treatment prophylaxis) provided during the post-discharge period to children recently admitted with severe anaemia is superior to reduce all-cause readmission and mortality rates by 6 months compared with 2 weeks of post-treatment prophylaxis provided by the single course of oral artemether-lumefantrine when given as part of the standard in-hospital care around the time of discharge.</div>\n<div>\n  </div>\n<div>\n Study Type: Multi-centre, 2-arm, placebo-controlled, individually randomized, trial of 3 courses of monthly PMC-DP in Uganda and Kenya, using randomisation stratified by age and study centre.</div>\n<div>\n  </div>\n<div>\n Sites: 7 hospitals, 4 in western Kenya and 3 in Uganda, in areas with moderate to intense malaria transmission. The number of hospitals will be expanded if recruitment if so required.</div>\n<div>\n  </div>\n<div>\n Study Population: Inclusion criteria: convalescent children aged less than 5 years and weighing >5 kg admitted with severe anaemia (haemoglobin<5g/dL / Ht<15%); clinically stable, able to take or switch to oral medication; post-transfusion Hb >5g/dL. Exclusion criteria: blood loss due to trauma, malignancy, known bleeding disorders or sickle cell trait, known hypersensitivity to study drug, known heart conditions, non-resident in study area, previous participation in study, known need at enrolment for prohibited medication and scheduled surgery during the 6-month course of the study. HIV infection and cotrimoxazole prophylaxis are not exclusion criteria.</div>\n<div>\n  </div>\n<div>\n Study Interventions: Children in both arms will receive standard in-hospital care for severe anaemia (blood transfusion, often combined with quinine or artesunate IV/IM). All children will then receive a 3-day course of AL (whether they initially had malaria or not), which will be started in-hospital assoon as they are able to take oral medication, and will be completed at home after discharge. At 2 weeks after enrolment surviving children will be randomized to receive either a standard 3-day courses of DP (Duo-Cotecxin®, HolleyCotec) or an identical placebo regimen at 2, 6 and 10 weeks after enrolment.</div>\n<div>\n  </div>\n<div>\n Outcome Measures: Primary: Death or all-cause re-admission between randomisation and 6 months from enrolment (composite primary outcome). Key secondary: 1) all-cause mortality, 2) all-cause hospital readmission, 3) readmissions due to severe anaemia or severe malaria (requiring parenteral quinine or artesunate), 4) non-severe all-cause sick-child clinic visits, 5) clinic visit because of RDT or microscopy confirmed non-severe malaria.</div>\n<div>\n  </div>\n<div>\n Follow-up procedures: Children will be followed for 6 months by passive case detection in 3 phases: Pre-PMC (2 weeks between discharge and randomisation); PMC (2-14 weeks post-discharge); post-PMC (extended follow period from 15 to 26 weeks post-discharge).</div>\n<div>\n Sample size: A sample size of 1106 children per arm (2212 total children) allows detection of a 30% reduction from 17.6% to 12.3% with 10% loss to follow-up (power 90%, α=0.05).</div>\n<div>\n  </div>\n<div>\n Data Analysis: Primary analysis will be by intention to treat, and include all events to capture the potential effect of PMC on reducing first and repeat events. The protective efficacy (95% CI) will be calculated as 100 multiplied by (1–hazard ratio) and covariate-adjusted for prognostic factors at baseline. Incidence rates per child-year and absolute rate reductions will also be calculated. To assess how long any initial beneficial effect of PMC is sustained, the observation time will also be divided into a) PMC period (1-3 months); and b) Extended follow-up period (4–6 months).</div>\n<div>\n  </div>\n<div>\n Partners institutions: University of Bergen; University of Malawi; Makerere University; KEMRI-CDC, Kenya; University of Minnesota; Liverpool School of Tropical Medicine; London School of Hygiene & Tropical Medicine; Imperial College London; University of Amsterdam; US Centers for Disease Control and Prevention, University of North Carolina, and University of Massachusetts.</div>\n
      • study_title<p>\n <span style=\"font-size:12px;\">Malaria Chemoprevention with monthly treatment with dihydroartemisinin-piperaquine for the post-discharge management of severe anaemia in children aged less than 5 years in Uganda and Kenya: A 3-year, multi-centre, parallel-group, two-arm randomised placebo controlled superiority trial</span></p>\n
      • laymans_summary<p>\n N/A</p>\n
      • short_titlePost-discharge Malaria Chemoprevention(PMC) study
      • protocol_noECCT/15/12/05
      • version_no2
      • date_of_protocol27-11-2014
      • study_drugPMC (DHA-Piperaquine)
      • disease_conditionMalaria
      • 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_nameDihydroartemisinin-piperaquine
      • product_type_medical_device_name
      • 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_data0
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter0
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african0
      • applicant_hard_copies(null)
      • applicant_signed_checklist0
      • statistical_analysis_plan1
      • applicant_contractual_agreement0
      • declaration_applicantDr Tony Sang
      • declaration_date115-12-2015
      • declaration_principal_investigatorDr Titus Kwambai
      • declaration_date215-12-2015
      • placebo_presentYes
      • study_objectives<p>\n <u> Primary objective</u></p>\n<ul>\n <li>\n To determine if 3 months of post-discharge malaria chemoprevention with monthly 3-day treatment courses of dihydroartemisinin-piperaquine (DP) (PMC-DP) is safe and superior to the standard single 3-day treatment course with artemether-lumefantrine provided as part of standard in-hospital care in reducing all-cause readmissions and deaths by 6 months in the post-discharge management of children less than 5 years of age admitted with severe anaemia.</li>\n</ul>\n<div>\n  </div>\n<div>\n <u>Secondary objectives</u></div>\n<ul>\n <li>\n To determine the cost-effectiveness of PMC-DP compared to current standard of care.</li>\n</ul>\n
      • principal_inclusion_criteria<div>\n Pre-study screening</div>\n<div>\n 1. Haemoglobin <5.0 g/dl or PCV < 15%, or requirement for blood transfusion for other clinical reasons on or during admission to the hospital</div>\n<div>\n 2. Aged less than 59.5 months</div>\n<div>\n 3. Body weight >5 kg</div>\n<div>\n 4. Resident in catchment area</div>\n<div>\n  </div>\n<div>\n Enrolment in study (t=0)</div>\n<div>\n 1. Fulfilled the pre-study screening eligibility criteria</div>\n<div>\n 2. Aged < 59.5 months</div>\n<div>\n 3. Clinically stable, able to take oral medication</div>\n<div>\n 4. Subject completed blood transfusion(s) or became clinically stable without transfusion</div>\n<div>\n 5. Able to feed (for breastfeeding children) or eat (for older children)</div>\n<div>\n 6. Absence of know cardiac problems</div>\n<div>\n 7. Provision of informed consent by parent or guardian</div>\n<div>\n  </div>\n<div>\n Randomisation (t=2 weeks)</div>\n<div>\n 1. Fulfilled enrolment eligibility criteria and was enrolled during recent admission</div>\n<div>\n 2. Aged <60 months</div>\n<div>\n 3. Still clinically stable, able to take to oral medication, able to feed (for breastfeeding children) or eat (for older children) and able to sit unaided (for older children who were already able to do so prior to hospitalisation)</div>\n
      • principal_exclusion_criteria<div>\n Pre-study screening</div>\n<ol>\n <li>\n Recognised specific other cause of severe anaemia (e.g. trauma, haematological malignancy, known bleeding disorder)</li>\n <li>\n Known sickle cell disease</li>\n <li>\n Anticipated to reach the 5th birthday (60 months of age) within 2 weeks from enrolment (i.e. prior to randomization)</li>\n <li>\n Child will reside for more than 25% of the 6 months study period (i.e. 6 weeks or more) outside of catchment area</li>\n</ol>\n<div>\n  </div>\n<div>\n Enrolment in study (t=0)</div>\n<ol>\n <li>\n Previous enrolment in the present study</li>\n <li>\n Known hypersensitivity to study drug</li>\n <li>\n Sickle cell disease</li>\n <li>\n Use or known need at the time of enrolment for concomitant prohibited medication (see section 8.5.7.2, page 34) during the 14 weeks PMC treatment period (see section 8.5.7.2, page 34).</li>\n <li>\n Ongoing or planned participation in another clinical trial involving ongoing or scheduled treatment with prohibited medicinal products or active follow-up during the course of the study (6 months from enrolment)</li>\n <li>\n A known need at the time of enrolment for scheduled surgery during the subsequent course of the study (6 months from enrolment)</li>\n <li>\n Suspected non-compliance with the follow-up schedule</li>\n <li>\n Know heart conditions, or family history of congenital prolongation of the QTc interval.</li>\n <li>\n Taking medicinal products that are known to prolong the QTc interval</li>\n</ol>\n<div>\n <div>\n  </div>\n <div>\n Randomisation (t=2 weeks)</div>\n <ol>\n <li>\n Used DP since enrolment</li>\n <li>\n Use or known need at the time of randomisation for concomitant prohibited medication (see section 8.5.7.2, page 34) during the 14 weeks PMC treatment period (see section 8.5.7.2, page 34).</li>\n <li>\n Enrolled, or known agreement to enrol into another clinical trial involving ongoing or scheduled treatment with medicinal products during the course of the study (6 months from enrolment)</li>\n <li>\n A known need at the time of randomisation for scheduled surgery during the subsequent course of the study (6 months from enrolment)</li>\n <li>\n Suspected non-compliance with the follow-up schedule</li>\n <li>\n Withdrawal of consent since enrolment</li>\n </ol>\n <div>\n  </div>\n</div>\n<p>\n  </p>\n
      • primary_end_points<p>\n Primary Outcome:</p>\n<ol>\n <li>\n All-cause deaths or all-cause re-admissions by 26 weeks from randomization (composite primary outcome)</li>\n</ol>\n<div>\n Key Secondary efficacy outcomes</div>\n<ol>\n <li>\n Readmission due to severe malaria (defined as any treatment with parenteral quinine or artesunate, or presence of severe anaemia and treatment with oral antimalarials) by 26 weeks from randomization</li>\n <li>\n Readmissions due to severe anaemia (defined as Hb <5g/dL or PCV <15% or requirement for blood transfusion based on other clinical indication) by 26 weeks from randomization</li>\n <li>\n Readmission due to severe malarial anaemia (severe anaemia plus parenteral or oral antimalarial treatment) by 26 weeks from randomization</li>\n <li>\n Readmission due to severe anaemia or severe malaria (composite outcome) by 26 weeks from randomization</li>\n <li>\n All-cause mortality by 26 weeks from randomization</li>\n <li>\n All-cause hospital readmission by 26 weeks from randomization</li>\n <li>\n Clinic visits because of smear of RDT confirmed non-severe malaria</li>\n</ol>\n<div>\n Safety outcomes</div>\n<ol>\n <li>\n Serious adverse events, excluding primary and secondary efficacy outcomes, by 26 weeks from randomization</li>\n <li>\n Serious adverse events within 7 days after the start of each course of PMC, excluding primary and secondary efficacy outcomes.</li>\n <li>\n Adverse events by 26 weeks from randomization</li>\n <li>\n Adverse events within 7 days after start of each course of PMC.</li>\n <li>\n QTc prolongation measured by electro cardio gram (ECG) 4-6 hours after 3rd dose of each course</li>\n</ol>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic1
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Th e study will beconducted  in four hospitals in western Kenya chosen from a list of Government or private (e.g. mission) hospitals in the previous Western and Nyanza Provinces, based on patient numbers, available infrastructure and malaria transmission and planned malaria control interventions in the catchment area.</p>\n<p>\n Study staff will include the following:</p>\n<ul>\n <li>\n Coordinating Investigator - Prof Feiko ter Kuile, MD, PhD</li>\n <li>\n PI - Dr Simon Kariuki, PhD</li>\n <li>\n PI - Dr Titus Kwambai, MBChB, MSc</li>\n <li>\n Co-Investigator - Dr Martina Oneko, MD (Paed)</li>\n <li>\n Co-Investigator - Dr Grace Nalwa, MD (Paed)</li>\n <li>\n Co-Investigator - Dr Magdalene Kuria, MD (Paed)</li>\n <li>\n Study Coordinator - Elizabeth Nyothach</li>\n <li>\n Pharmacist - Dr Tony Sang, BPharm</li>\n <li>\n Data manager - Wycliffe Odongo</li>\n <li>\n Clinical officers x 8 persons</li>\n <li>\n Community Interviewers x 9 persons</li>\n</ul>\n
      • other_details_explanation
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n KEMRI Scientific & Ethics Review Unit approved the trial on 20-Nov-2015</p>\n<p>\n Makerere School of Medicine Research Ethics Commitee approved the trial on 20-Oct-2015</p>\n<p>\n Liverpool School of Tropical Medicine(LSTM) Research Ethics Commitee approved the trial on 14-Dec-2015</p>\n<p>\n  </p>\n
      • other_details_regulatory_rejected
      • other_details_regulatory_halted
      • estimated_duration2.5 years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • 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_states2
      • number_of_sites4
      • multi_country_listKenya\nUganda
      • data_monitoring_committeeYes
      • total_enrolment_per_siteEnrollment expected to be 250 participants for each Kenyan site.\n
      • total_participants_worldwide2212
      • 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_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyMinor participants i.e. below 18 years of age for whom Informed Consent Form will be signed by their legally acceptable representative. In addition, in accordance with local regulation, minors ≥13 years old with capacity for writing could will sign off on an assent Form.
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameProf Feiko
      • investigator1_middle_name
      • investigator1_family_nameter Kuile
      • investigator1_qualificationMD, PhD
      • investigator1_professional_addressKEMRI/CDC and LSTM, P.O. Box 1578, Kisumu 40100,
      • investigator1_telephone+254 708 739 228
      • investigator1_emailfeiko.terkuile@lstmed.ac.uk
      • organisations_transferred_No
      • number_participants1000
      • notification
      • approval_date24-02-2016
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted26-01-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p align=\"center\">\n <strong><u>FINAL STUDY SUMMARY/ END OF STUDY REPORT</u></strong></p>\n<p>\n <strong>Title of Proposal:</strong> <em>Malaria Chemoprevention with monthly treatment with dihydroartemisinin-piperaquine for the post-discharge management of severe anaemia in children aged less than 5 years in Uganda and Kenya: A 3-year, multi-centre, parallel-group, two-arm randomized placebo controlled superiority trial</em></p>\n<p>\n <strong>Principal Investigator(s):</strong> <em>Dr Titus Kwambai (co-PI) and Dr Simon Kariuki (co-PI), and </em><em>Prof Feiko ter Kuile (CI)</em></p>\n<p>\n <strong>Centre:</strong> <em>KEMRI, Centre for Global Health Research, Kisumu</em></p>\n<p>\n  </p>\n<p>\n <strong>SERU/NON-SERU/SSC/NON-SSC No.:</strong></p>\n<ol style=\"list-style-type:lower-alpha;\">\n <li>\n <em><strong>SERU:</strong></em><em> KEMRI SERU Protocol No: 2965 </em></li>\n <li>\n <em><strong>NON-SERU:</strong></em>\n <ul>\n <li>\n <em>Liverpool School of Tropical Medicine (LSTM) Research Ethics Committee, UK, Research Protocol No: 14.034 </em></li>\n <li>\n <em>School of Medicine, Research and Ethics Committee (SOMREC), Makerere University College of Health Sciences, Makerere, Uganda.</em></li>\n </ul>\n </li>\n</ol>\n<p style=\"margin-left:54.0pt;\">\n  </p>\n<p>\n <strong>1. Date of scientific and ethics (SERU/SSC/NON-SSC) approval: </strong></p>\n<ol style=\"list-style-type:lower-alpha;\">\n <li>\n <em><strong>SERU:</strong></em>\n <ol>\n <li>\n <em>08 Sep 2015: Protocol (v1.2-25Aug15)</em></li>\n <li>\n <em>20 Nov 2015: Protocol amendment (v2-[amendment]-12Nov15)</em></li>\n <li>\n <em>11 Nov 2016: Protocol amendment (v3-[amendment]-28Oct16)</em></li>\n <li>\n <em>04 Feb 2018: Protocol amendment (v4-[amendment]-06Feb18)</em></li>\n </ol>\n </li>\n <li>\n <em><strong>NON-SERU:</strong></em>\n <ol>\n <li>\n <em>Liverpool School of Tropical Medicine (LSTM) Research and Ethics Committee, Liverpool UK (trial sponsor).</em>\n <ol style=\"list-style-type:lower-roman;\">\n <li>\n <em>14 Dec 2015: Protocol amendment (v2-[amendment]- </em></li>\n <li>\n <em>05 Dec 2016: Protocol amendment (v3-[amendment]-28Oct16)</em></li>\n <li>\n <em>13 Apr 2018: Protocol amendment (v4-[amendment]-06Feb18</em></li>\n </ol>\n </li>\n <li>\n <em>School of Medicine, Research and Ethics Committee (SOMREC), Makerere University College of Health Sciences.</em>\n <ol style=\"list-style-type:lower-roman;\">\n <li>\n <em>05 Feb 2016: Protocol amendment (v2-[amendment]-12Nov15)</em></li>\n <li>\n <em>13 Dec 2016: Protocol amendment (v3-[amendment]-28Oct16)</em></li>\n <li>\n <em>27 Jul 2018: Protocol amendment (v4-[amendment]-06Feb18)</em></li>\n </ol>\n </li>\n </ol>\n </li>\n</ol>\n<p style=\"margin-left:18.0pt;\">\n  </p>\n<ol style=\"list-style-type:lower-roman;\">\n <li>\n <strong>Date the study stopped collecting data where applicable:</strong></li>\n</ol>\n<ul>\n <li>\n Date for the last participant was recruited (and enrolment): 24 Apr 2018</li>\n <li>\n Date the last follow up was made. 06 Nov 2018</li>\n</ul>\n<p style=\"margin-left:54.0pt;\">\n  </p>\n<p>\n <strong>2. The copy the last continuing review approval or initial approval if this is the first request for renewal:</strong></p>\n<p>\n <em>See attachments of the last annual approval by SERU dated Sep 05, 2018; this was for protocol v4 (amendment) 06Feb18. Please also find included a copy of the SERU approval (dated 15 Mar 2018) of the currently active protocol (v4-[amendment]-06Feb18).</em></p>\n<p>\n  </p>\n<p>\n <strong>3.Project period covered: </strong><em>This report covers the period between: 20 Sep 2018 to 19 Sep 2019.</em></p>\n<p>\n  </p>\n<p>\n <strong>4. Research objectives: </strong></p>\n<p>\n <em><strong>Objective: </strong></em><em>To determine if 3 months of post-discharge malaria chemoprevention with monthly, 3-day treatment courses of dihydroartemisinin-piperaquine (DP) (PMC-DP) is safe and superior to the standard single 3-day treatment course with artemether-lumefantrine provided as part of standard in-hospital care in reducing all-cause readmissions and deaths by 6 months in the post-discharge management of children less than 5 years of age admitted with severe anaemia.</em></p>\n<p>\n <em><strong>Study Location:</strong></em><em> This is a two-country trial conducted in hospitals in Kenya and Uganda.</em></p>\n<p>\n  </p>\n<p>\n <strong>5. Research progress summary: </strong></p>\n<p style=\"margin-left:18.0pt;\">\n <em>Participant enrolment and follow-up completed</em></p>\n<p style=\"margin-left:18.0pt;\">\n  </p>\n<p style=\"margin-left:18.0pt;\">\n  </p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:100.0%;\" width=\"100%\">\n <tbody>\n <tr>\n <td colspan=\"4\" style=\"width:77.86%;height:36px;\">\n <ol>\n <li>\n <strong><em>Site Information and Recruitment</em></strong></li>\n </ol>\n </td>\n <td style=\"width:22.14%;height:36px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:30.52%;height:36px;\">\n <p>\n <strong><em>Number of sites</em></strong></p>\n </td>\n <td style=\"width:21.36%;height:36px;\">\n <p>\n <em>2</em></p>\n </td>\n <td style=\"width:25.98%;height:36px;\">\n <p>\n <strong><em>Recruitment status</em></strong></p>\n </td>\n <td style=\"width:22.14%;height:36px;\">\n <p>\n <em>Recruiting</em></p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:30.52%;height:36px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:21.36%;height:36px;\">\n <p>\n <strong><em>Uganda</em></strong></p>\n </td>\n <td style=\"width:25.98%;height:36px;\">\n <p>\n <strong><em>Kenya</em></strong></p>\n </td>\n <td style=\"width:22.14%;height:36px;\">\n <p>\n <strong><em>Total</em></strong></p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:30.52%;height:36px;\">\n <p>\n <strong><em>Target recruitment</em></strong></p>\n </td>\n <td style=\"width:21.36%;height:36px;\">\n <p>\n <em>Competitive recruitment</em></p>\n </td>\n <td style=\"width:25.98%;height:36px;\">\n <p>\n <em>Competitive recruitment</em></p>\n </td>\n <td style=\"width:22.14%;height:36px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:30.52%;height:36px;\">\n <p>\n <strong><em>Randomized</em></strong></p>\n </td>\n <td style=\"width:21.36%;height:36px;\">\n <p>\n <em>692</em></p>\n </td>\n <td style=\"width:25.98%;height:36px;\">\n <p>\n <em>357</em></p>\n </td>\n <td style=\"width:22.14%;height:36px;\">\n <p>\n <em>1049</em></p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:30.52%;height:36px;\">\n <p>\n <strong><em>Follow-up Status</em></strong></p>\n </td>\n <td style=\"width:21.36%;height:36px;\">\n <p>\n <em> completed</em></p>\n </td>\n <td style=\"width:25.98%;height:36px;\">\n <p>\n <em> completed</em></p>\n </td>\n <td style=\"width:22.14%;height:36px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:3.88%;height:36px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:26.64%;height:36px;\">\n <p>\n <strong><em>Completed 6m</em></strong></p>\n </td>\n <td style=\"width:21.36%;height:36px;\">\n <p>\n <em>661</em></p>\n </td>\n <td style=\"width:25.98%;height:36px;\">\n <p>\n <em>282</em></p>\n </td>\n <td style=\"width:22.14%;height:36px;\">\n <p>\n <em>943</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:3.88%;height:36px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:26.64%;height:36px;\">\n <p>\n <strong><em>Died</em></strong></p>\n </td>\n <td style=\"width:21.36%;height:36px;\">\n <p>\n <em>20</em></p>\n </td>\n <td style=\"width:25.98%;height:36px;\">\n <p>\n <em>10</em></p>\n </td>\n <td style=\"width:22.14%;height:36px;\">\n <p>\n <em>30</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:3.88%;height:36px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:26.64%;height:36px;\">\n <p>\n <strong><em>Lost to follow-up (LTFU)</em></strong></p>\n </td>\n <td style=\"width:21.36%;height:36px;\">\n <p>\n <em>7</em></p>\n </td>\n <td style=\"width:25.98%;height:36px;\">\n <p>\n <em>52</em></p>\n </td>\n <td style=\"width:22.14%;height:36px;\">\n <p>\n <em>59</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:3.88%;height:36px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:26.64%;height:36px;\">\n <p>\n <strong><em>Consent withdrawn</em></strong></p>\n </td>\n <td style=\"width:21.36%;height:36px;\">\n <p>\n <em>4</em></p>\n </td>\n <td style=\"width:25.98%;height:36px;\">\n <p>\n <em>5</em></p>\n </td>\n <td style=\"width:22.14%;height:36px;\">\n <p>\n <em>9</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:3.88%;height:36px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:26.64%;height:36px;\">\n <p>\n <strong><em>Screening error withdrawal</em></strong></p>\n </td>\n <td style=\"width:21.36%;height:36px;\">\n <p>\n <em>0</em></p>\n </td>\n <td style=\"width:25.98%;height:36px;\">\n <p>\n <em>8</em></p>\n </td>\n <td style=\"width:22.14%;height:36px;\">\n <p>\n <em>8</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:3.88%;height:36px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:26.64%;height:36px;\">\n <p>\n <strong><em>Total LTFU/withdrawn</em></strong></p>\n </td>\n <td style=\"width:21.36%;height:36px;\">\n <p>\n <em>11</em></p>\n </td>\n <td style=\"width:25.98%;height:36px;\">\n <p>\n <em>65</em></p>\n </td>\n <td style=\"width:22.14%;height:36px;\">\n <p>\n <em>76</em></p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n <strong>6. Amendments: </strong></p>\n<p>\n <em>Three amendments have so far been made and approved by all ethics committees.</em></p>\n<ul>\n <li>\n <em>The first amendment to the protocol (v2-12Nov15) was made before participant recruitment was commenced. The amendment included a change in the brand of dihydroartemisinin-piperaquine from Duo-Cotecxin (Holley Cotec, China) to the GMP formulation Eurartesim® from Sigma Tau, Italy. The dosing schedule for dihydroartemisinin-piperaquine was also updated to follow the revised dose recommendation made by the World Health Organization. </em></li>\n <li>\n <em>The second amended Protocol (v3-[amendment]-28Oct16), was reviewed by SERU on 29 Nov 2016. The amendment included expansion of the number of study sites, clarifications on the participant information sheets, consent forms and minor typological errors in the protocol.</em></li>\n <li>\n <em> The third amended Protocol (v4-[amendment]-06Feb18), was reviewed by SERU on 13 Mar 2018. This included the revision of sample size from 2212 to 1040 overall; 1106 to 520 per arm. This was based on DMEC and TSC recommendation due to a lower than expected rate of loss to follow-up and a higher than expected pooled event rate of the composite primary endpoint across both arms.</em></li>\n</ul>\n<p>\n  </p>\n<p>\n <strong>7. Adverse events reports: (</strong><em>See attached SAE line list)</em></p>\n<p>\n <em>We expected to generate >500 SAEs in this study. This was due to the nature of the study which involved a high-risk study population (children admitted with severe anaemia are at high risk of post-discharge events) and a primary endpoint that itself fulfilled the criteria of an SAE (i.e. death or rebound hospital admission by 6 month). </em></p>\n<p>\n  </p>\n<p>\n <em>By the end of participant follow-up on 6^th Nov, 2018 there was a total of 581 serious adverse events (SAEs) overall from Kenya and Uganda, including 30 deaths. In summary, the SAEs were as following:</em></p>\n<ul>\n <li>\n <em>No fatalities were reported to be related to the study intervention</em></li>\n <li>\n <em>No SUSAR was reported </em></li>\n <li>\n <em>2 events (anaemia) were reported by investigators as possibly related to the study drug dihydroartemisinin-piperaquine (DHA‐PQ).</em></li>\n <li>\n <em>All other SAEs were reported as unrelated to DHA-PQ</em></li>\n</ul>\n<p>\n <em>All events from both countries were reported in an expedited manner to the Data Safety Monitoring Board (DSMB) and the Research and Ethics Committee (REC) of LSTM (the sponsor), and all events in Kenya were also reported to SERU (KEMRI) and all events in Uganda were reported to SOMREC (Makerere). All SAEs were expected given the high-risk study population.  </em></p>\n<p>\n  </p>\n<p>\n <strong>8. Projects outputs: </strong><em>No project outputs yet, the manuscript is nearly completd.</em></p>\n<p>\n  </p>\n<p>\n <strong>9. Constraints: </strong></p>\n<ol style=\"list-style-type:lower-alpha;\">\n <li>\n <em>Our recruitment rate was lower than expected due to </em>\n <ol style=\"list-style-type:lower-roman;\">\n <li>\n <em>acute shortage of blood for transfusion in Western Kenya. This is mainly due to inadequate number of donations especially during the school holiday seasons and occasional shortage of reagents used for screening the blood at the regional blood Banks. Low numbers of potential participants are therefore seen at the study hospitals (referral centres) possibly due to low referral rates from peripheral facilities. Some are referred to private facilities if they have blood for transfusion. We have assisted in blood drives to collect blood for Migori, Homa Bay and Siaya referral hospitals. </em></li>\n <li>\n <em>Following the roll-out of the indoor residual spraying activities in Migori County, we prematurely closed the Migori site because of the drastic reduction in the number of potential participants and event rates. </em></li>\n </ol>\n </li>\n</ol>\n<p>\n  </p>\n<p>\n <strong>10. Any other relevant information: </strong></p>\n<p>\n <em>A continuation approval is not required.</em></p>\n<p>\n  </p>\n<p>\n <strong>11. Plans for the next project year: </strong></p>\n<ol style=\"list-style-type:lower-alpha;\">\n <li>\n <em>Completion of manuscript writing and publication of results</em></li>\n <li>\n <em>Dissemination of study findings to various groups </em>\n <ol style=\"list-style-type:lower-alpha;\">\n <li>\n <em>Health management teams of the 4 host counties and study participants</em></li>\n <li>\n <em>Presentation of findings to the division of malaria control at the ministry of health and other partners</em></li>\n <li>\n <em>Presentation of finding at major conferences e.g American Society of Tropical Health and Hygiene (ASTMH 2019).</em></li>\n </ol>\n </li>\n</ol>\n<p>\n  </p>\n
      • implication_results
      • quantity_imported22,242 x DHA-Piperaquine tabs/placebo 20/160mg and 7,980 x DHA-Piperaquine tabs/placebo 40/320mg
      • quantity_dispensed2,951 x DHA-Piperaquine tabs/placebo 20/160mg and 1,563 x DHA-Piperaquine tabs/placebo 40/320mg
      • quantity_destroyedNone
      • quantity_exportedNone
      • balance_site19,291 x DHA-Piperaquine tabs/placebo 20/160mg and 6,417 x DHA-Piperaquine tabs/placebo 40/320mg
      • final_date0000-00-00
      • modified2021-03-01 11:15:20
      • created2015-10-01 13:53:50
      • total_sites(null)
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        • application_id424
        • given_nameTitus
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        • family_nameKwambai
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        • professional_addressKEMRI Centre for Global Health Research (CGHR), P.O. Box 1578, Kisumu 40100
        • telephone+254 723354238
        • emailtkkwambai@gmail.com
        • created2015-10-01 14:05:13
        • modified2021-01-26 12:14:49
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        • given_nameSimon
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        • family_nameKariuki
        • qualificationPhD
        • professional_addressKEMRI Centre for Global Health Research (CGHR), P.O. Box 1578, Kisumu 40100
        • telephone+ 254 725 389 246
        • emailskariuki@kemricdc.org
        • created2015-10-21 12:41:46
        • modified2021-01-26 12:14:49
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        • created2015-10-01 14:05:13
        • modified2021-01-26 12:14:49
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          • modified2012-06-15 10:26:56
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          • created2012-06-15 10:27:10
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        • created2015-10-21 12:56:47
        • modified2021-01-26 12:14:49
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        • site_nameBusia County Referral Hospital
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        • contact_detailsP.O. Box 87-50400
        • contact_personDr Barnabas Kigen
        • site_capacity(null)
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        • created2015-11-05 16:06:02
        • modified2021-01-26 12:14:49
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          • created2012-06-15 10:26:51
          • modified2012-06-15 10:26:51
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        • id224
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        • sponsorLiverpool School of Tropical Medicine (LSTM)
        • sponsor_typeResearch Institution
        • contact_person
        • addressPembroke Place, Liverpool L3 5QA, UK
        • telephone_number+44 0151 7053212
        • fax_number
        • cell_number+44 0151 7053212
        • email_addressS.Roberts@liverpool.ac.uk
        • created2015-10-01 14:05:13
        • modified2021-01-26 12:14:49
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