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      • id1248
      • user_id828
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      • abstract_of_study<div class=\"page\" title=\"Page 3\">\n <div class=\"section\">\n <div class=\"layoutArea\">\n <div class=\"column\">\n <p>\n <span style=\"font-size: 12.000000pt; font-family: \'TimesNewRomanPSMT\'\">Our solution will aim at clinical use for epilepsy diagnosis and the main innovation is delivering an EEG device that is usable by non-experts with minimal training paired with an EEG recording service, not only the EEG device. We will provide an easy-to-use and end-to- end solution for epilepsy diagnostic support. Our solution is aimed at the ~70% of epilepsy cases that can be diagnosed “easily” (Smith, 2005; WHO, 2019). Our recording system, the BrainCapture-1 (BC-1) consists of 4 parts: An electrode cap in 3 sizes, an amplifier, an app, and cloud storage. This intervention is an affordable solution that 1) allows nurses with minimal extra training to perform recordings at remote locations and 2) assists local doctors to make diagnosis and treatment decisions by providing an EEG report. To make this happen, the solution will be robust to all kinds of conditions, like weather and cultural difficulties in interpreting the user interface. </span></p>\n </div>\n </div>\n </div>\n</div>\n<p>\n  </p>\n
      • study_title<div class=\"page\" title=\"Page 1\">\n <div class=\"layoutArea\">\n <div class=\"column\">\n <p>\n <span style=\"font-size: 12.000000pt; font-family: \'TimesNewRomanPS\'; font-weight: 700\">Usability and efficacy of an affordable, smartphone-connected EEG device to bridge the global gap in epilepsy diagnosis </span></p>\n </div>\n </div>\n</div>\n<p>\n  </p>\n
      • laymans_summary<div class=\"page\" title=\"Page 3\">\n <div class=\"section\">\n <div class=\"layoutArea\">\n <div class=\"column\">\n <p>\n <span style=\"font-size: 12.000000pt; font-family: \'TimesNewRomanPSMT\'\">One percent of the population worldwide has epilepsy (Fiest, et al., 2017). EEG is the most important diagnostic tool for patients with seizures and suspected epilepsy. However, it is unavailable to the majority of the global population because the equipment is expensive (in the order of tens of thousands of Euros) and expertise for data-capture and interpretation is lacking (Mehndiratta & Wadhai, 2015). Around 80% of people with epilepsy live in resource-poor countries (Leonardi & Ustun, 2002), and around 75% are not treated (Meyer, Dua, Ma, Saxena, & Birbeck, 2010). The World Health Organization (WHO) estimates that up to 70% of these people live seizure free life if properly diagnosed and treated (Smith, 2005; WHO, 2019). To bridge this diagnostic and treatment gap and improve the quality of care for most of the world’s inhabitants, the study team has developed an easy-to-use, portable, smartphone connected EEG device that uses a smart phone to facilitate data collection and remote interpretation. This intervention has been tested previously in Sub- Saharan Africa, specifically in the Republic of Guinea (Williams et al.., 2019). In this trial, we target non-expert medical workers at the Aga Khan University Hospital in Nairobi, specifically nurses as a user group. If this group is able to use our device to take high-quality EEG, then our device can effectively address a large portion of disease burden by separating data collection and interpretation. </span></p>\n </div>\n </div>\n </div>\n</div>\n<p>\n  </p>\n
      • short_titleBrainCapture EEG Validation
      • protocol_noECCT/23/05/03
      • version_no1
      • date_of_protocol10-02-2023
      • study_drugnone
      • disease_conditionEpilepsy
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device1
      • product_type_chemical_name
      • product_type_medical_device_nameEEG
      • comparatorYes
      • comparator_nameNihon Khoden
      • comparator_registeredYes
      • comparator_countriesKenya and all other countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressp.loomis@braincapture.dk
      • applicant_covering_letter1
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      • declaration_applicantPaul Loomis
      • declaration_date105-05-2023
      • declaration_principal_investigatorDr. Dilraj Sokhi
      • declaration_date205-05-2023
      • placebo_presentNo
      • study_objectives<p>\n To demonstrate the usability and efficacy of an affordable, easy-to-use portable electroencephalography (EEG) device that yields essential electrodiagnostics for patients with seizures and suspected epilepsy in settings with limited access to experts. We have already developed a portable, Bluetooth enabled amplifier device that has obtained technical CE-mark approval in the European Union, is FDA-approved, and has been tested in a Sub-Saharan African setting (the Republic of Guinea; Williams et al., 2019). In this project, we aim to assess the usability and efficacy of the device by evaluating the quality of recordings completed by non-expert health workers.</p>\n
      • principal_inclusion_criteria<p>\n <strong><em>Phase I:</em></strong></p>\n<p>\n <em>Inclusion criteria:</em></p>\n<p>\n 1)    Meeting the International League Against Epilepsy (ILAE) definition of epilepsy;</p>\n<p>\n 2)    Ages 2 to 80 years;</p>\n<p>\n 3)    Willingness to undergo two separate EEG exams;</p>\n<p>\n 4)    Ability to provide informed consent (either self or as legal representative of subject)</p>\n<p>\n  </p>\n<p>\n <strong><em>Phase II:</em></strong></p>\n<p>\n <em>Inclusion criteria:</em></p>\n<p>\n 1)    presenting to Aga Khan at first seizure with a clinical suspicion of epilepsy</p>\n<p>\n 2)    Ages 2 to 80 years;</p>\n<p>\n 3)    Willingness to undergo two separate EEG exams;</p>\n<p>\n 4)    Ability to provide informed consent (either self or as legal representative of subject)</p>\n
      • principal_exclusion_criteria<p>\n Phase 1:</p>\n<p>\n <em>Exclusion criteria:</em></p>\n<p>\n 1)    Any other diagnosis that can better explain the symptoms, making the diagnosis of epilepsy unlikely; unable to undergo the study procedures;</p>\n<p>\n 2)    Age <2 years old due to lack of electrode cap for small head size;</p>\n<p>\n 3)    Health or practical issues impeding data collection as determined at the discretion of the examiner (e.g., hairstyle that precludes electrode contact with scalp or undue risk presented by photic stimulation);</p>\n<p>\n  </p>\n<p>\n Phase II:</p>\n<p>\n <em>Exclusion criteria:</em></p>\n<p>\n 1)    Any other diagnosis that can better explain the symptoms, making the diagnosis of epilepsy unlikely; unable to undergo the study procedures;</p>\n<p>\n 2)    Age <2 years old due to lack of electrode cap for small head size;</p>\n<p>\n 3)    Health or practical issues impeding data collection as determined at the discretion of the examiner (e.g., hairstyle that precludes electrode contact with scalp or undue risk presented by photic stimulation)</p>\n<p>\n Because eligibility criteria for Phases I and II are mutually exclusive, we do not expect any participants from Phase I to be eligible nor participate in Phase II of this trial.</p>\n
      • primary_end_points<p>\n Phase I is expected to commence in October 2022. Phase II will commence after data has been completely collected and undergone analysis from Phase I, expected to be between January and June 2023. The trial endpoint will be considered when the intended sample size is achieved for each phase of the trial. We anticipate recruitment, enrollment, data collection, and data analysis for both phases of the trial will take approximately 15 months to complete.</p>\n
      • scope_diagnosis1
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      • trial_human_pharmacology0
      • trial_administration_humans0
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      • trial_other1
      • trial_other_specifyValidation of a diagnostic
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n STUDY SITE<br />\n <br />\n The study will be conducted at the Aga Khan University Hospital, Nairobi, 3rd Parklands Avenue Nairobi.<br />\n <br />\n The Neurology section at AKUHN, under the department of Medicine, is well- staffed by trained personnel with expertise in the following research-related tasks<br />\n <br />\n <br />\n •                           Clinical Nursing: Collect medical information; Vital signs; Collect adverse events; Collect lab samples; Participant recruitment and retention.<br />\n <br />\n •                           Pharmacy Technologist: Manage IP receipt/return;<br />\n <br />\n - Neurologists: all GCP certified and compliant with institutional research ethics and conduct requirements. Obtain Informed Consent; Assess eligibility; Make CRF entries/resolve Queries; Medical decisions/review; Collect medical information; Vital signs; Assess Ordinal Scale; Collect/Assess Adverse Events; Administer IP; Conduct Physical Exam; Collect Lab Samples; Maintain Essential Documents; IP processes<br />\n <br />\n •                           Contracts and Budgets: Maintain legal and financial documents; Ensure appropriate invoicing to the sponsor; Ensure appropriate processes for research covered procedures versus patients’ standard of care<br />\n <br />\n • The neurology section has specialists who provide quality care to patients with a variety of neurological complaints such as; headache, epilepsy, strokes, change in behavior and cognition, neurological infections, Parkinson’s disease, dementia including Alzheimer’s disease, spinal cord injury, neuromuscular disorders including myopathy and myasthenia gravis, and neuro-inflammatory disorders including multiple sclerosis and sleep disorders.<br />\n <br />\n <br />\n The team of neurologists works closely with other allied healthcare professionals in physiotherapy, occupational therapy, speech and language therapy and nutritionists to deliver comprehensive care for their patients.<br />\n <br />\n <br />\n The Neurological teams work in close relationship with our other sections, including the Departments of Radiology, Pathology, Nutrition and Laboratory, ensuring a multidisciplinary and expedited approach to patient care.<br />\n <br />\n <br />\n All patients treated at AKUHN have access to psychosocial and support counselling as part of AKUH, N best practice. This is not limited to non-study patients and thus is available to study patients as well.<br />\n <br />\n <br />\n <br />\n The AKUH, N approach to care is guided by core principles of Quality, Access, Impact and Relevance and its healthcare practices are of the highest quality, as benchmarked against international standards including accreditation by:<br />\n <br />\n •                           Joint Commission International (JCI)<br />\n <br />\n •                           College of American Pathologists (CAP)<br />\n <br />\n •                           International Quality Assurance 9001:2008<br />\n <br />\n •                           South African National Accreditation Service (SANAS)</p>\n
      • other_details_explanation<p>\n Capture develops products and technology that target emerging markets. The EEG diagnostic is rare in much of the world, but not in Braincapture's home market of Denmark, where traditional EEG devices and experts are plentiful. Therefore, this validation study seeks to demonstrate and validate BrainCapture's approach to EEG in a market which it tends to address with its product.</p>\n
      • other_details_regulatory_notapproved<p>\n None </p>\n
      • other_details_regulatory_approved<p>\n None</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration6 Months
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorAga Khan EEG Lab
      • 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 Ave
      • single_site_contact_personDilraj Sokhi
      • single_site_telephone+254 710 559 541
      • multiple_sites_member_stateNo
      • multiple_countriesNo
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      • data_monitoring_committeeNo
      • total_enrolment_per_site200
      • total_participants_worldwide200
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
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      • investigator1_given_nameDiraj Sokhi
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      • investigator1_professional_address3rd Parklands Ave, Nairobi, Kenya
      • investigator1_telephone+254 710 559 541
      • investigator1_emaildilraj.sokhi@aku.edu
      • organisations_transferred_No
      • number_participants200
      • notification
      • approval_date20-12-2023
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      • date_submitted29-09-2023
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      • modified2023-12-20 09:24:22
      • created2023-04-03 17:35:12
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        • given_nameDiraj Sokhi
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        • professional_address3rd Parklands Ave, Nairobi, Kenya
        • telephone+254 710 559 541
        • emaildilraj.sokhi@aku.edu
        • created2023-04-12 10:50:02
        • modified2023-09-29 14:10:53
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        • id658
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        • sponsorBrainCapture Aps
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        • contact_personPaul Loomis
        • addressFuturebox, DTU, Elektrovej 331, DK-2800 Kongens Lyngby, Denmark
        • telephone_number0799920707
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        • email_addressp.loomis@braincapture.dk
        • created2023-04-12 10:50:02
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      • abstract_of_study<div>\n DESIGN</div>\n<div>\n A5384 is a Phase II randomized, open-label trial to compare a 6-month regimen of high-dose rifampicin (RIF), high-dose isoniazid (INH), linezolid (LZD), and pyrazinamide (PZA) to the World Health Organization (WHO) 9-month standard of care (SOC) regimen for the treatment of tuberculous meningitis (TBM).</div>\n<div>\n  </div>\n<div>\n DURATION</div>\n<div>\n 72 weeks</div>\n<div>\n  </div>\n<div>\n SAMPLE SIZE</div>\n<div>\n 330 participants</div>\n<div>\n  </div>\n<div>\n POPULATION</div>\n<div>\n Participants living with and without HIV co-infection, with definite, probable, or possible TBM, aged ≥15 years.</div>\n<div>\n  </div>\n<div>\n STRATIFICATION</div>\n<div>\n Participants will be stratified by HIV status and TBM disease stage, as defined by the modified British Medical Research Council (BMRC) Classification TBM Grade.</div>\n<div>\n Grade I: Glasgow Coma Score 15, no focal neurological deficits</div>\n<div>\n Grade II: Glasgow Coma Score 11-14 or 15 with focal neurological deficits</div>\n<div>\n Grade III: Glasgow Coma Score ≤10</div>\n<div>\n  </div>\n<div>\n REGIMEN</div>\n<div>\n Participants will be randomized 1:1 to one of two arms:</div>\n<div>\n <u>Arm A:</u> RIF 35 mg/kg + INH 15 mg/kg + LZD 1200 mg + PZA 25 mg/kg for 2 weeks, followed by RIF 35 mg/kg + INH 10 mg/kg + LZD 1200 mg + PZA 25 mg/kg for 6 weeks, and then RIF 35 mg/kg and INH 10 mg/kg for 16 weeks, for a total of 24 weeks of study treatment.</div>\n<div>\n <u>Arm B:</u> WHO SOC: RIF 10 mg/kg + INH 5 mg/kg + ethambutol (EMB) 20 mg/kg + PZA 25 mg/kg for 8 weeks, followed by RIF 10 mg/kg and INH 5 mg/kg for 28 weeks, for a total of 36 weeks of study treatment. Up to 15 mg/kg or a maximum of 900 mg daily of oral RIF will be permitted in this arm at clinician’s discretion.</div>\n<div>\n All participants will receive pyridoxine, while on INH, and adjunctive corticosteroids (as provided by standard of care [SOC], not provided by the study) according to disease severity for at least 6 weeks.</div>\n
      • study_title<p>\n A Phase II, Randomized, Open-Label Trial of a Six-Month Regimen of High-Dose Rifampicin, High-Dose Isoniazid, Linezolid, and Pyrazinamide versus a Standard Nine-Month Regimen for the Treatment of Adults and Adolescents with Tuberculous Meningitis: Improved Management with Antimicrobial AGents Isoniazid rifampiciN LinEzolid for TBM (IMAGINE-TBM)</p>\n
      • laymans_summary<p>\n TBM is a devastating illness with high risk of mortality and severe neurologic morbidity. Although recent data suggest that significant dose increases in RIF may improve outcomes in TBM, mortality remains high, and enhanced treatment strategies are needed. In addition, limited data are available to guide treatment duration in adults with TBM. The overall goal of the proposed trial is to assess the PK, safety, and longitudinal treatment outcomes of an optimized 6-month regimen of high-dose RIF, high-dose INH, LZD, and PZA to the WHO 9-month SOC regimen for the treatment of TBM.</p>\n
      • short_titleA5384
      • protocol_noECCT/23/05/02
      • version_no1.0
      • date_of_protocol03-11-2021
      • study_drugRifampicin, Isoniazid, Linezolid, Pyrazinamide
      • disease_conditionTuberculous Meningitis
      • 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_nameRifampicin, Isoniazid, Linezolid, Pyrazinamide
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressviola.kirui@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
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      • applicant_complete_form(null)
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      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantFlorence Njulu
      • declaration_date105-05-2023
      • declaration_principal_investigatorAbraham M. Siika
      • declaration_date205-05-2023
      • placebo_presentNo
      • study_objectives<div>\n 1.2 Primary Objective</div>\n<div>\n To determine if a regimen of high-dose RIF, high-dose INH, LZD, and PZA improves functional outcomes measured by the modified Rankin Scale (mRS) at 48 weeks compared with WHO SOC for the treatment of TBM.</div>\n<div>\n  </div>\n<div>\n 1.3 Secondary Objectives</div>\n<div>\n 1.3.1 To determine if a regimen of high-dose RIF, high-dose INH, LZD, and PZA improves functional outcomes measured by the mRS at 12, 24, 36, and 72 weeks compared with WHO SOC for the treatment of TBM.</div>\n<div>\n 1.3.2 To determine if a regimen of high-dose RIF, high-dose INH, LZD, and PZA improves longitudinal functional outcomes compared with WHO SOC for the treatment of TBM.</div>\n<div>\n 1.3.3 To determine if a regimen of high-dose RIF, high-dose INH, LZD, and PZA improves mortality at 48 and 72 weeks compared with WHO SOC for the treatment of TBM.</div>\n<div>\n 1.3.4 To determine the safety and tolerability of administration of high-dose RIF, high-dose INH, LZD, and PZA at 8 weeks for the treatment of TBM.</div>\n<div>\n 1.3.5 To compare neurocognitive outcomes at 24 and 48 weeks in participants randomized to high-dose RIF, high-dose INH, LZD, and PZA versus WHO SOC.</div>\n<div>\n 1.3.6 To evaluate the effect of high-dose RIF on the cerebrospinal fluid (CSF) and plasma pharmacokinetics (PK) of LZD.</div>\n<div>\n 1.3.7 To determine if RIF, INH, LZD, and PZA exposures in CSF and plasma predict functional outcomes and mortality.</div>\n<div>\n 1.3.8 To compare Patient Health Questionnaire (PHQ-9) total score and WHO Disability Assessment Schedule (WHO DAS) score at 24, 48, and 72 weeks.</div>\n<div>\n <div>\n 1.3.9 To compare change in BMRC TBM grade at week 1.</div>\n <div>\n 1.3.10 To compare time to coma clearance, which is defined as Glasgow Coma Score of 15 for ≥48 hours for hospitalized participants over 4 weeks.</div>\n <div>\n 1.3.11 To compare time to new neurological event, which is defined as fall in Glasgow Coma Score of ≥2 points for ≥48 hours for hospitalized participants or since last visit for non-hospitalized participants, new onset seizures, new focal neurologic deficit over 48 weeks.</div>\n <div>\n 1.3.12 To determine if a regimen of high-dose RIF, high-dose INH, LZD, and PZA improves functional outcomes measured by the mRS at 48 weeks compared with WHO SOC for the treatment of TBM among those with definite TB meningitis and among those with definite or probable TB meningitis.</div>\n <div>\n 1.4 Exploratory Objectives</div>\n <div>\n 1.4.1 To compare relapse rates 12 weeks after completion of study treatment between a 24-week treatment regimen versus the 36-week WHO SOC regimen.</div>\n <div>\n 1.4.2 To evaluate the CSF microbiologic, molecular and inflammatory response to high-dose RIF, high-dose INH, LZD, and PZA versus WHO SOC at 2 weeks and 6-8 weeks in TBM.</div>\n <div>\n 1.4.3 To investigate the value of Xpert Ultra and semiquantitative testing for lipoarabinomannan (LAM) in CSF and urine for the diagnosis and treatment monitoring of TBM.</div>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n 4.1.1 Definite, probable, or possible TBM diagnosis wherein the participant is being committed to a full course of SOC anti-TB treatment for TBM in the setting of routine care. CSF, imaging, laboratory, and other results used to determine definite, probable, or possible TBM can be from testing performed as part of routine care, as long as obtained within 21 days prior to study entry.</p>\n<div>\n 4.1.2 Persons aged ≥15 years</div>\n<div>\n 4.1.3 Absence of HIV-1 infection, as documented by any licensed rapid HIV test or HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit, within 30 days prior to study entry,</div>\n<div>\n OR</div>\n<div>\n HIV-1 infection, documented by any licensed rapid HIV test or HIV-1 E/CIA test kit at any time prior to entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load. Two or more HIV-1 RNA viral loads of >1,000 copies/mL are also acceptable as documentation of HIV-1 infection, or documentation of HIV diagnosis in the medical record by a healthcare provider.</div>\n<div>\n <div>\n 4.1.4 Documentation within 3 days prior to study entry of stage of disease using BMRC TBM grade:</div>\n <div>\n Grade I: Glasgow Coma Score 15, no focal neurological deficits</div>\n <div>\n Grade II: Glasgow Coma Score 11-14 or 15 with focal neurological deficits</div>\n <div>\n Grade III: Glasgow Coma Score ≤10</div>\n <div>\n 4.1.5 The following laboratory values obtained within 3 days prior to study entry:</div>\n <div>\n • Serum creatinine ≤1.8 times upper limit of normal (ULN)</div>\n <div>\n • Hemoglobin ≥8.0 g/dL for men, ≥7.5 g/dL for women</div>\n <div>\n • Absolute neutrophil count ≥600/mm3</div>\n <div>\n • Platelet count ≥60,000/mm3</div>\n <div>\n • Alanine aminotransferase (ALT) ≤3 x ULN</div>\n <div>\n • Total bilirubin ≤2 x ULN</div>\n <div>\n 4.1.6 For participants of reproductive potential who have not been post-menopausal for at least 24 consecutive months (i.e., no menses within the preceding 24 months), or participants who have not undergone surgical sterilization, hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal ligation, documentation of a serum or urine pregnancy test result (positive or negative; see section 6.3.6 for test sensitivity requirement) within 21 days prior to study entry.</div>\n <div>\n Note: Acceptable documentation of lack of reproductive potential is oral or written documentation from the participant.</div>\n <div>\n 4.1.7 Participants with documentation of a positive pregnancy test will be consented using the consent form for pregnant participants (Appendix V).</div>\n <div>\n  </div>\n</div>\n<div>\n 4.1.8 Ability and willingness of participant or parent or legally authorized representative (for adolescents or participants unable to provide consent) to provide informed consent/assent.</div>\n<div>\n 4.1.9 Ability to comply with the protocol requirements in the opinion of the site investigator.</div>\n
      • principal_exclusion_criteria<div>\n 4.2.1 More than 14 cumulative days of first-line TB medications, including but not limited to INH, RIF, EMB, and PZA, received within 90 days prior to study entry.</div>\n<div>\n Note: INH used as prophylaxis is allowed.</div>\n<div>\n 4.2.2 Known current or previous drug resistant TB infection (i.e., resistance to one or more first-line TB medications, including but not limited to INH, RIF, EMB, LZD and PZA).</div>\n<div>\n 4.2.3 Known allergy/sensitivity or any hypersensitivity to components of study TB drugs (INH, RIF, LZD, PZA, and EMB) or their formulation.</div>\n<div>\n 4.2.4 For participants who are able to undergo the Brief Peripheral Neuropathy Screen (BPNS) within 21 days prior to study entry, Grade 3 subjective peripheral neuropathy score on the BPNS AND EITHER vibratory loss OR absent ankle jerks.</div>\n<div>\n <div>\n 4.2.5 Expected concomitant use or use up to 21 days prior to study entry of monoamine oxidase inhibitors or selective serotonin reuptake inhibitors, or concomitant use of any other drug with significant interaction with the study drugs (see section 5.4.2).</div>\n <div>\n 4.2.6 For participants with HIV and ART-naïve, planned initiation of ART during the first 4 weeks after randomization.</div>\n <div>\n 4.2.7 For participants with HIV and on ART that includes a protease inhibitor, nevirapine, or other prohibited ART (see section 5.4.2), contraindication to switching to an acceptable alternative regimen (e.g., efavirenz, high-dose raltegravir or dolutegravir with nucleoside reverse transcriptase inhibitors, as per local SOC) prior to randomization. TB treatment, including study drugs, should be started as soon as possible.</div>\n <div>\n 4.2.8 Contraindication to LP at discretion of treating clinician (e.g., unequal pressures between intracranial compartments due to mass lesion, non-communicating hydrocephalus).</div>\n <div>\n 4.2.9 Positive cryptococcal antigen, gram stain, bacterial culture, or other test result obtained from a CSF specimen collected within 21 days prior to entry as part of routine care indicating CNS infection with a pathogen other than Mtb (e.g.,</div>\n <div>\n cryptococcal meningitis, bacterial meningitis). Refer to section 14 of the A5384 MOPS.</div>\n</div>\n<p>\n  </p>\n
      • primary_end_points<p>\n Modified Rankin Scale (6-death, 5-severe disability, 4-moderately severe disability, 3-moderate disability, 2-slight disability, 1-no significant disability, 0-no symptoms) at 48 weeks</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • 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<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Prof. Abraham M. Siika                                 Site Leader/ Principal Investigator</li>\n <li style=\"line-height: 20px;\">\n Dr. Charity Wamboi                                         Co- Investigator</li>\n <li style=\"line-height: 20px;\">\n Getrude Jerop Kiptoo                                              Study Clinician          </li>\n <li style=\"line-height: 20px;\">\n Vincent KIpchirchir                                                Study Clinician                      </li>\n <li style=\"line-height: 20px;\">\n Philemon Kipchirchir Mutai                                     Study Nurse</li>\n <li style=\"line-height: 20px;\">\n Chris Sande                                                   Study Nurse</li>\n <li style=\"line-height: 20px;\">\n Damaris Lagat                                           Quality Assurance/Control officer</li>\n <li style=\"line-height: 20px;\">\n Shauri Gona                                              Recruitment officer</li>\n <li style=\"line-height: 20px;\">\n Julie Choge                                                     Recruitment officer</li>\n <li style=\"line-height: 20px;\">\n Florence Njulu                                            regulatory Officer</li>\n <li style=\"line-height: 20px;\">\n Wilson Ekiru                                                  Assistant data manger</li>\n <li style=\"line-height: 20px;\">\n Martha Mokaya                                             Data manger           </li>\n <li style=\"line-height: 20px;\">\n Natalie Sang                                         Pharmacist of record</li>\n <li style=\"line-height: 20px;\">\n Beatrice Jakait                                               Backup pharmacist</li>\n <li style=\"line-height: 20px;\">\n Salina Cherutich                                            Pharmaceutical technologist</li>\n <li style=\"line-height: 20px;\">\n Vincent Onyango                                           Phlebotomist</li>\n</ol>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">The outcome of this trial will have major public health implications for areas of the world with high burdens of TBM. The sponsor Country (US) does not fall in this category.</span></p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Moi Teaching and Referral Hospital/Moi University Institutional Research and Ethics Committee (IREC). Approval granted on January 26 2023 for the Eldoret site.</span></p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration72 Weeks per participant
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorStandard of Care
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states5
      • number_of_sites2
      • multi_country_listMalawi, Brazil,\nSouth Africa, Peru
      • data_monitoring_committeeYes
      • total_enrolment_per_site0 - 330
      • total_participants_worldwide330
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenYes
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifySome participnats may be enrolled while incapacitated.
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameAbraham
      • investigator1_middle_nameMosigisi
      • investigator1_family_nameSiika
      • investigator1_qualificationMBCHB, MMed, MSc
      • investigator1_professional_addressP.O.BOX 4606-30100
      • investigator1_telephone+254721280785
      • investigator1_emailabrahamsiika@gmail.com
      • organisations_transferred_No
      • number_participants40 at the Eldoret site
      • notification
      • approval_date12-10-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted05-05-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-01-22 15:05:25
      • created2023-03-28 12:12:59
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id916
        • application_id1241
        • given_nameAbraham
        • middle_name
        • family_nameSiika
        • qualificationMBChB, MMed, MSc
        • professional_addressP.O Box 4606-30100 Eldoret Kenya
        • telephone254721280785
        • emailabrahamsiika@gmail.com
        • created2023-03-28 12:39:01
        • modified2023-05-05 13:26:44
    • SiteDetail(array)
      • 0(array)
        • id1465
        • application_id1241
        • county_id27
        • site_nameMoi University Clinical Research Centre
        • physical_addressChandaria Cancer and Chronic Diseases Centre at MTRH
        • contact_detailsP.O. BOX 4606-30100
        • contact_personFlorence Njulu
        • site_capacity(null)
        • misc(null)
        • created2023-03-28 12:39:01
        • modified2023-05-05 13:26:44
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
      • 1(array)
        • id1466
        • application_id1241
        • county_id35
        • site_nameKEMRI Walter Reed Project
        • physical_addressKericho County Hospital Grounds
        • contact_details0722941525
        • contact_personMary Lelgo
        • site_capacity(null)
        • misc(null)
        • created2023-03-28 13:09:24
        • modified2023-05-05 13:26:44
        • County(array)
          • id35
          • county_nameKericho
          • created2012-06-15 10:26:16
          • modified2012-06-15 10:26:16
    • Sponsor(array)
      • 0(array)
        • id653
        • application_id1241
        • sponsorNational Institute of Allergy and Infectious Diseases
        • sponsor_typeOthers
        • contact_personGavin Churchyard, MBBCh, MMed, FRCP, FCP(SA), PhD
        • addressPostnet Suite 300, Private Bag X30500, Houghton, 2041 SOUTH AFRICA
        • telephone_number+27 (0) 10 590 1306
        • fax_number
        • cell_number+27 (0) 10 590 1306
        • email_addressgchurchyard@auruminstitute.org
        • created2023-03-28 12:39:01
        • modified2023-05-05 13:26:44
  • 2(array)
    • Application(array)
      • id1234
      • user_id21
      • trial_status_id2
      • abstract_of_study<p style=\"margin-left:99.0pt;\">\n <u>DESIGN</u>                   A5356 is a phase II, prospective, randomized, two-arm, open-label, multicenter clinical trial to evaluate the anti-tuberculosis (TB) activity, safety, and tolerability of an injectable-free short course regimen for treatment of multidrug-/rifampicin-resistant (MDR-/RR-), pre-extensively drug-resistant (pre-XDR-), and extensively drug-resistant (XDR-) TB comparing two dosing strategies of linezolid (LZD) combined with bedaquiline (BDQ), delamanid (DLM), and clofazimine (CFZ).</p>\n<p>\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <u>DURATION</u>              72 weeks total: at least 26 weeks (6 months) of anti-TB treatment, with up to 46 weeks of follow-up.</p>\n<p>\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <u>SAMPLE SIZE</u>         132 participants (66 per treatment arm)</p>\n<p>\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <u>POPULATION</u>          Participants aged 18 years and older, with or without HIV, with newly diagnosed pulmonary MDR/RR-TB, pre-XDR-TB, or XDR-TB (collectively noted as DR-TB in the protocol).</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n Participants may be enrolled with a positive rapid diagnostic test for MDR/RR-TB such as Cepheid Xpert MTB/RIF, Cepheid Xpert MTB/RIF Ultra, Hain GenoType MTBDR<em>plus</em>, Hain GenoType MTBDR<em>sl</em>, or other World Health Organization (WHO)-endorsed rapid diagnostic test or with screening phenotypic drug susceptibility testing (DST) from a sputum specimen collected within 60 days prior to entry.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n Participants living with HIV are required to either be on ART or be willing to start ART within 30 days after entry.</p>\n<p>\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <u>REGIMENS</u>              At entry, all participants will be randomized 1:1 to one of two treatment arms (Arm A or Arm B). The only difference in treatment between the two arms is the dosing schedule for LZD, as shown below.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <u>Arm A</u></p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 1-26: LZD 600 mg once daily (QD)</p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 1-2: BDQ 200 mg QD + DLM 300 mg QD + CFZ 300 mg QD</p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 3-8: BDQ 200 mg QD + DLM 300 mg QD + CFZ 100 mg QD</p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 9-26 or -38: BDQ 100 mg QD + DLM 300 mg QD + CFZ 100 mg QD</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <u>Arm B</u></p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 1-4: LZD 1200 mg QD</p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 5-26: LZD 1200 mg three times per week (TIW)</p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 1-2: BDQ 200 mg QD + DLM 300 mg QD + CFZ 300 mg QD</p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 3-8: BDQ 200 mg QD + DLM 300 mg QD + CFZ 100 mg QD</p>\n<p style=\"margin-left:99.0pt;\">\n Weeks 9-26 or -38: BDQ 100 mg QD + DLM 300 mg QD + CFZ 100 mg QD</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n Participants who do not achieve sputum culture conversion by 16 weeks of treatment will extend their treatment by an additional 12 weeks for a total treatment duration of 38 weeks.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n
      • study_title<p align=\"center\">\n A Phase II, Prospective, Randomized, Multicenter Trial to Evaluate the Efficacy and Safety/Tolerability of Two Linezolid Dosing Strategies in Combination with a Short Course Regimen for the Treatment of Drug-Resistant Pulmonary Tuberculosis</p>\n
      • laymans_summary<p>\n This is a research study. Participants who will be  approached regarding this research study will have tuberculosis (TB) that is resistant to some of the drugs generally used to treat it. The purpose of the study is to evaluate the efficacy (how well the medicines work) and tolerability (the level and type of side effects from a drug or treatment) of two different treatment regimens that contain the same four anti-TB medicines: linezolid (LZD), bedaquiline (BDQ), delamanid (DLM), and clofazimine (CFZ). This study will also measure the level of these medicines in your blood.</p>\n<div>\n <div>\n <p>\n Hypothesis;  Linezolid (LZD) administered at an initial dose of 1200 mg daily for 4 weeks followed by 1200 mg three times per week (TIW), plus bedaquiline (BDQ), delamanid (DLM), and clofazimine (CFZ) will be associated with more rapid sputum culture conversion and acceptable rates of treatment discontinuations due to adverse events (AEs), intolerance, and death compared to LZD administered at a dose of 600 mg daily in combination with BDQ, DLM, and CFZ.</p>\n <div>\n The 2 primary objectives are to 1.Compare time to sputum culture conversion in liquid media between treatment arms. And 2 To estimate the occurrence of permanent discontinuation of at least one anti-TB drug due to AEs, intolerance, or death within each treatment arm.</div>\n <p>\n  </p>\n </div>\n <div>\n <div>\n  </div>\n <div>\n <div>\n  </div>\n <div>\n  </div>\n </div>\n </div>\n</div>\n<p>\n  </p>\n
      • short_titleA5356
      • protocol_noECCT/23/05/01
      • version_no1.0
      • date_of_protocol05-04-2021
      • study_drugLinezolid
      • disease_conditionDrug-Resistant Pulmonary Tuberculosis
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameLinezolid
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressviola.kirui@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantFlorence Njulu
      • declaration_date104-05-2023
      • declaration_principal_investigatorAbraham M. Siika
      • declaration_date204-05-2023
      • placebo_presentNo
      • study_objectives<h2>\n  </h2>\n<p>\n <span style=\"font-size:12px;\">   Primary Objectives</span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:times new roman,times,serif;\">1. To compare time to sputum culture conversion in liquid media between treatment arms.</span></span></p>\n<p>\n <span style=\"font-size: 12px;\"><span style=\"font-family:times new roman,times,serif;\">2. To estimate the occurrence of permanent discontinuation of at least one anti-TB drug due to AEs, intolerance, or death within each treatment arm</span>.</span></p>\n<p>\n  Secondary Objectives</p>\n<p>\n 1. To compare proportion with sputum culture conversion in liquid media at 8, 16, 26, and 38 weeks between treatment arms.</p>\n<p>\n 2.To compare permanent discontinuation of LZD due to AEs, intolerance, or death, temporary discontinuation of LZD for any reason, and dose reductions for LZD between treatment arms.</p>\n<p>\n 3. To compare the occurrence of treatment-related AEs between treatment arms.</p>\n<p>\n 4. To compare the occurrence of unfavorable TB treatment outcome at weeks 26, 38 (for those who extend treatment by 12 weeks), and 72 between treatment arms.</p>\n<p>\n 5. To determine LZD pharmacokinetic (PK) parameters for each LZD dosing strategy.</p>\n<p>\n 6.To determine DLM PK parameters within each treatment arm.</p>\n<p>\n 7. To compare adherence to LZD, BDQ, DLM, and CFZ between treatment arms as determined by recording of the number of observed doses based on directly observed therapy (DOT).</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n
      • principal_inclusion_criteria<p style=\"margin-left:72.0pt;\">\n 1    Aged ≥18 years of age at screening.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 2    Newly diagnosed pulmonary drug-resistant TB (DR-TB), with resistance to at least RIF as determined by either genotypic (such as Cepheid Xpert MTB/RIF, Cepheid Xpert MTB/RIF Ultra, Hain GenoType MTBDR<em>plus</em>, Hain GenoType MTBDR<em>sl</em>, or other WHO-endorsed rapid diagnostic test) or with the results of phenotypic drug susceptibility testing (DST) from a sputum specimen collected within 60 days prior to entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE: DR-TB diagnosis for purposes of meeting inclusion criteria can be from a network-approved study testing laboratory or from an outside laboratory.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 3    HIV-1 infection status documented as either absent or present, as defined below:</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n Absence of HIV-1 infection, as documented by any licensed rapid HIV test or HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit, within 60 days prior to entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n OR</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n HIV-1 infection, documented by any licensed rapid HIV test or HIV-1 E/CIA test kit at any time prior to entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load. Two or more HIV-1 RNA viral loads of >1,000 copies/mL are also acceptable as documentation of HIV infection.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE A: The term “licensed” refers to a US FDA-approved kit, which is recommended. For sites that are unable to obtain an FDA-approved kit, a kit that has been certified or licensed by an oversight body within the country and validated internally is acceptable.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE B: WHO and US Centers for Disease Control and Prevention (CDC) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 4    For participants living with HIV, either currently on an ART regimen or willing and able to start ART within 30 days after entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE: For a list of excluded ARV medications, refer to <a href=\"#_APPENDIX_I:_A5356\">Appendix I</a>.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 5    Efavirenz or etravirine must be discontinued prior to a participant’s starting anti‑TB medications. For participants on efavirenz or etravirine, they must be willing and able to discontinue these at least 7 days prior to initiating study TB medications.</p>\n<p style=\"margin-left:36.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 6    For participants living with HIV, CD4+ cell count ≥50 cells/mm³obtained within 60 days prior to study entry at any network-approved non-US laboratory that is Immunology Quality Assurance (IQA) certified. </p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 7    For females of reproductive potential, negative serum or urine pregnancy test within 7 days prior to entry at any network-approved laboratory or clinic that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs.</p>\n<p style=\"margin-left:108.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE: Urine test must have a sensitivity of ≤25 mIU/mL.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 8    Females of reproductive potential who are participating in sexual activity that could lead to pregnancy must agree to use two of the following forms of birth control while receiving TB study medications and for 30 days after stopping study medications:</p>\n<ul>\n <li>\n Male or female condoms</li>\n <li>\n Diaphragm or cervical cap (with spermicide, if available)</li>\n <li>\n Intrauterine device (IUD) or intrauterine system (IUS)</li>\n <li>\n Hormone-based birth control (e.g., oral contraceptives, Depo-Provera, NuvaRing, implants) </li>\n</ul>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE: Females who are not of reproductive potential are eligible without requiring the use of contraceptives. Self-reported history is acceptable documentation of menopause (i.e., at least 1 year amenorrheic), hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; these candidates are all considered not of reproductive potential.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 9    The following laboratory values obtained within 14 days prior to entry at any network-approved laboratory that operates in accordance with Good Clinical Laboratory Practice (GCLP) standards and participates in appropriate external quality assurance programs:</p>\n<ol style=\"list-style-type:lower-alpha;\">\n <li>\n Creatinine ≤1.5 x upper limit normal (ULN)</li>\n <li>\n Absolute neutrophil count (ANC) ≥800/mm³</li>\n <li>\n Hemoglobin level of >8.5 gm/dL for females and >9.0 gm/dL for males </li>\n <li>\n Platelet count ≥100,000 cells/mm³</li>\n <li>\n Alanine aminotransferase (ALT) <2.5 x ULN</li>\n <li>\n Alkaline phosphatase (ALP) <2.5 x ULN; ≥2.5 – 8.0 x ULN <strong>may enroll per the investigator’s discretion after discussion with </strong>the team</li>\n <li>\n Total bilirubin ≤2.0 x ULN, or ≤1.50 x ULN if AST, ALT or ALP is above the ULN but no higher than a Grade 1 level</li>\n <li>\n Potassium level ≥3.4 mEq/L</li>\n <li>\n Negative for HBsAg and HCV antibody</li>\n <li>\n Calculated creatinine clearance (CrCl) >50 mL/min, as estimated by the Cockcroft-Gault equation.</li>\n</ol>\n<p style=\"margin-left:36.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE A: Calculator for the Cockcroft-Gault equation is available at <u>https://www.frontierscience.org/apps/cfmx/apps/common/Portal/index.cfm.</u></p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE B: Any laboratory value that excludes the candidate may be repeated to confirm eligibility. The repeated laboratory value will be excluded from the required >24‑hour window between screening and entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 10  Karnofsky performance score ³50 within 30 days prior to entry.</p>\n<p style=\"margin-left:36.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 11  Ability and willingness of candidate and/or legal guardian/representative to provide informed consent and meet requirements for the study.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 12  Chest X-ray obtained within 30 days prior to entry.</p>\n
      • principal_exclusion_criteria<p style=\"margin-left:72.0pt;\">\n 1    Documentation of clinically significant (as judged by the site investigator) active infections (including HIV-related opportunistic infections) other than TB and HIV requiring treatment within 30 days prior to entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 2    Evidence of clinically significant (as judged by the site investigator) metabolic, gastrointestinal, cardiovascular, musculoskeletal, ophthalmological, pulmonary, neurological, psychiatric, endocrine diseases, malignancy, or other abnormalities (other than the indication being studied) that would interfere with study medications or procedures.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 3    Inability to take oral medications.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 4    Suspected or documented TB involving the central nervous system, clinically significant renal TB or TB pericarditis, or current extrapulmonary TB involving other organ systems that might interfere with study medications or procedures, as judged by the site investigator.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 5    Prior treatment with LZD, DLM, BDQ, or CFZ at any time in the past for an episode of DR-TB that is not the qualifying episode <u>or</u> treatment for more than 7 cumulative days with one or more of LZD, DLM, BDQ, or CFZ within <u>30</u> days prior to entry for the qualifying episode of DR-TB.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE: For the qualifying episode of DR-TB, candidates may receive up to 7 cumulative days of presumptive TB treatment that includes LZD, DLM, BDQ, or CFZ within 30 days prior to entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 6    History of allergy or hypersensitivity to any of the study drugs or medications in the same class as the study drugs.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 7    Known or suspected current alcohol and/or drug abuse that is, in the opinion of the site investigator, sufficient to compromise the safety and/or cooperation of the participant.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 8    Receipt of any investigational drugs within 60 days prior to entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 9    Known history of prolonged QT syndrome or current QTcF interval >450 ms on screening ECG.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 10  Known history of clinically significant cardiac arrhythmia requiring medication or clinically significant ECG abnormality, in the opinion of the site investigator, within 60 days prior to entry, including but not limited to second or third degree atrioventricular (AV) block or prolongation of the QRS complex interval over 120 ms.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 11  Pregnancy or current breastfeeding, or intent to become pregnant and/or breastfeed while on study treatment.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 12  Current use of monoamine oxidase inhibitors or use within 30 days prior to entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 13  Current use of serotonergic agents including SSRI/SNRI antidepressants or prior use within 30 days prior to entry.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 14  Known history of optic neuropathy of any grade as diagnosed by an ophthalmologist.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n 15  Current peripheral neuropathy Grade ≥2.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:36.0pt;\">\n               16  Weight <35 kg.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:36.0pt;\">\n               17 Currently taking other prohibited medications.</p>\n<p style=\"margin-left:72.0pt;\">\n  </p>\n<p style=\"margin-left:72.0pt;\">\n NOTE: Refer to <a href=\"#_APPENDIX_I:_A5356\">Appendix I</a> for a list of prohibited medications.</p>\n
      • primary_end_points<h2 style=\"page-break-after:auto\">\n <span lang=\"EN-US\" style=\"font-size: 11pt; font-family: Arial, sans-serif;\">Anticipated Outcomes<o:p></o:p></span></h2>\n<p>\n The pharmacologic evaluations will provide information on the steady-state PK of the LZD, DLM, and other TB regimen components in both study arms. The measures of drug exposure determined from the PK data will be used to evaluate the relationship between the PK parameters achieved in two study arms and study outcomes</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Prof. Abraham M. Siika                                 Site Leader/ Principal Investigator</li>\n <li style=\"line-height: 20px;\">\n Dr. Charity Wamboi                                         Co- Investigator</li>\n <li style=\"line-height: 20px;\">\n Getrude Jerop Kiptoo                                              Study Clinician          </li>\n <li style=\"line-height: 20px;\">\n Vincent KIpchirchir                                                Study Clinician                      </li>\n <li style=\"line-height: 20px;\">\n Philemon Kipchirchir Mutai                                     Study Nurse</li>\n <li style=\"line-height: 20px;\">\n Chris Sande                                                   Study Nurse</li>\n <li style=\"line-height: 20px;\">\n Damaris Lagat                                           Quality Assurance/Control officer</li>\n <li style=\"line-height: 20px;\">\n Shauri Gona                                              Recruitment officer</li>\n <li style=\"line-height: 20px;\">\n Julie Choge                                                     Recruitment officer</li>\n <li style=\"line-height: 20px;\">\n Florence Njulu                                            regulatory Officer</li>\n <li style=\"line-height: 20px;\">\n Wilson Ekiru                                                  Assistant data manger</li>\n <li style=\"line-height: 20px;\">\n Martha Mokaya                                             Data manger           </li>\n <li style=\"line-height: 20px;\">\n Natalie Sang                                         Pharmacist of record</li>\n <li style=\"line-height: 20px;\">\n Beatrice Jakait                                               Backup pharmacist</li>\n <li style=\"line-height: 20px;\">\n Salina Cherutich                                            Pharmaceutical technologist</li>\n <li style=\"line-height: 20px;\">\n Vincent Onyango                                           Phlebotomist</li>\n</ol>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">The outcome of this trial will have major public health implications for areas of the world with high burdens of MDR-TB. The sponsor Country (US) does not fall in this category.</span></p>\n
      • other_details_regulatory_notapproved<p>\n <font color=\"#333333\" face=\"Trebuchet MS, Tahoma, Verdana, Arial, sans-serif\"><span style=\"font-size: 12.5px;\">n/a</span></font></p>\n
      • other_details_regulatory_approved<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Moi Teaching and Referral Hospital/Moi University Institutional Research and Ethics Committee (IREC). Approval granted on 15 December 2022 for the Eldoret site.</span></p>\n
      • other_details_regulatory_rejected<p>\n n/a</p>\n
      • other_details_regulatory_halted<p>\n n/a</p>\n
      • estimated_duration72 weeks
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorbedaquiline, delamanid, c
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaMOI UNIVERSITY CLINICAL RESEARCH CENTRE
      • single_site_physical_addressP.O.BOX 4606-30100
      • single_site_contact_personViola Kirui
      • single_site_telephone+254711729856
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states7
      • number_of_sites
      • multi_country_listSOUTH AFRICA, BRAZIL, BOTSWANA, HAITU, THAILAND, PHILIPINES, PERU
      • data_monitoring_committeeYes
      • total_enrolment_per_siten/a
      • total_participants_worldwide132
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameAbraham
      • investigator1_middle_nameMosigisi
      • investigator1_family_nameSiika
      • investigator1_qualificationMBCHB, MMed, MSc
      • investigator1_professional_addressP O BOX 4606-30100
      • investigator1_telephone+254721280785
      • investigator1_emailabrahamsiika@gmail.com
      • organisations_transferred_No
      • number_participants30
      • notification
      • approval_date06-03-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted04-05-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-03-13 13:13:49
      • created2023-03-07 13:43:59
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id915
        • application_id1234
        • given_nameAbraham
        • middle_nameMosigisi
        • family_nameSiika
        • qualificationMBCHB, MMed, MSc
        • professional_addressP O BOX 4606-30100
        • telephone+254721280785
        • emailabrahamsiika@gmail.com
        • created2023-03-28 10:18:03
        • modified2023-05-04 15:30:25
    • SiteDetail(array)
      • 0(array)
        • id1464
        • application_id1234
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2023-03-28 10:18:03
        • modified2023-05-04 15:30:25
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id652
        • application_id1234
        • sponsorNational Institute of Allergy and Infectious Diseases
        • sponsor_typeOthers
        • contact_personGavin Churchyard, MBBCh, MMed, FRCP, FCP(SA), PhD
        • addressPostnet Suite 300, Private Bag X30500, Houghton, 2041 SOUTH AFRICA
        • telephone_number+27 (0) 10 590 1306
        • fax_number+27 (0) 86 613 3718
        • cell_number+27 (0) 10 590 1306
        • email_addressgchurchyard@auruminstitute.org
        • created2023-03-28 10:18:03
        • modified2023-05-04 15:30:25
  • 3(array)
    • Application(array)
      • id1257
      • user_id81
      • trial_status_id5
      • abstract_of_study<p>\n SARS-C-oV-2 infection driven COVID-19 cases and associated deaths continue to be reported around the world, indicating a persistent risk for waves of increased transmission, previously characterised by high levels of hospitalisations with severe disease, and death. SARS-CoV-2 virus also continues to evolve, with the Omicron (and it’s sub-lineages), now being the dominant variant globally. The sequential changes in SARS-CoV-2 virus are associated with structural modifications that confer the newly evolved variants the ability for immune escape from vaccine induced immunity. Indeed, there is now evidence that Omicron variants and their sub-lineages can escape from neutralisation of antibodies induced from either prior immunisation with the original BNT162b2 (Pfizer-BioNTech) vaccine, implying a causal link with a reduction in vaccine effectiveness. Furthermore, the original BNT162b2 (similar with other COVID-19) vaccine(s) induced protection is also short-lived, necessitating the sequential administrations of additional vaccine doses (now called “booster immunisations”) to extend and broaden protection from the primary vaccination series. One way to overcome these challenges of the reducing vaccine efficacy associated with either SARS-CoV-2 evolution, and/or a rapidly decaying immune response, is to add components of the current dominant Omicron variant to the original vaccine, as this would extend the initial protection to last longer, whilst also broadening it to cover more SARS-CoV-2 variants. Therefore, the new generation of COVID-19 vaccines are bivalent: combining components of the original Wuhan-Hu-1 and at least one or more of the current Omicron variants. The Pfizer bivalent BNT162b2 COVID-19 vaccine (containing components of the Wuhan-Hu-1 and Omicrons BA.4 and BA.5), being tested here, is currently approved for booster vaccinations in high income countries. However, it has not been formerly tested in unvaccinated individuals. While there are many regional variations in COVID-19 epidemiology, most of Africans are seropositive for SARS-CoV-2 owing to natural infection rather than vaccination. Concurrently, COVID-19 vaccination coverage remains very low in Africa. It is unclear if one dose of the bivalent vaccine will be sufficient to provide protection against Omicron variants and their sub-lineages in sub–Saharan African populations. We propose a clinical trial comparing safety and immunogenicity of the bivalent BNT162b2 COVID-19 vaccine with the corresponding original BNT162b2 (monovalent) COVID-19 vaccine in previously unvaccinated sub-Saharan Africa adults. The evidence generated will guide policies for the rational use of bivalent and the original mRNA vaccines in COVID-19 control. </p>\n
      • study_title<p>\n <span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">A randomised, controlled clinical trial to assess and compare the immunogenicity, safety and reactogenicity of the bivalent</span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\"> </span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">Omicron </span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">BA.4/BA.5</span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\"> </span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">adapted</span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">,</span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\"> and the </span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">original </span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">Wuhan-Hu-1-strain</span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">,</span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\"> BNT162b2 COVID-19 vaccine</span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\"> formulations</span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\"> in healthy unvaccinated East African </span><span class=\"NormalTextRun SCXW36608480 BCX8\" data-ccp-parastyle=\"Title\" style=\"margin: 0px; padding: 0px; user-select: text; -webkit-user-drag: none; -webkit-tap-highlight-color: transparent; font-family: "Times New Roman", "Times New Roman_EmbeddedFont", "Times New Roman_MSFontService", serif; font-size: 16px; font-variant-ligatures: none; font-weight: 700; white-space: pre-wrap;\">adults.</span></p>\n
      • laymans_summary<p align=\"left\">\n COVID-19 virus infections and cases continue to be reported from most regions around the world, including Africa. Thus, waves of increased COVID-19 virus spreading, which are often characterised by high levels of hospitalisations with severe disease and deaths will remain a major risk for now, and in the future. Besides the large numbers of COVID-19 attributable hospitalisations and deaths that occurred in large cities like Nairobi and Dar es Salaam in 2020 and 2021, data from the Kilifi Demographic Surveillance show increased mortality among older adults since the beginning of the pandemic suggesting that increased vaccination coverage in rural areas may enhance their protection, as well as those with underlying chronic diseases.</p>\n<address>\n COVID-19 virus also continues to evolve, with the Omicron variant now being the dominant strain globally. Sequential changes (over time) in the virus makeup are associated with structural modifications that increase its transmissibility, and in the case of Omicron, immune escape from vaccine induced immunity. Because the currently available COVID-19 vaccines were optimized for protection against the originally described (ancestral) COVID-19 virus strain, it is likely that they will be rendered less effective against COVID-19 associated with Omicron and other future variants.  Furthermore, the vaccine induced protection also wanes with time, necessitating the administrations of additional vaccine doses to fully vaccinated people to extend the protection afforded by the primary immunisation series.</address>\n<address>\n One way to overcome the challenges of waning vaccine efficacy, owing to the introduction of new COVID-19 virus variants and passage of time, is to add components of the Omicron variant to the original vaccines, so that the new generation of “bivalent” vaccines are also optimised to protect against the more recently evolved COVID-19 virus variants. Vaccine manufacturers are now making these bivalent vaccines, and the one from Pfizer-BioNTech is already approved for use in some countries, and already in the market for COVID-19 control.  Until now, this vaccine has only been tested in previously COVID-19 vaccinated individuals, as additional booster vaccine doses.</address>\n<address>\n For now, it also unclear if two doses of the new bivalent vaccines are necessary to provide sufficient protection against Omicron variants in populations where exposure to COVID-19 virus infection has been very high but with very low vaccine coverage, like in Kenya and Tanzania. Thus, this study will generate data indicating whether unvaccinated, but SARS-CoV-2 exposed adults can be sufficiently protected by single doses of the new vaccine. Importantly, if the new bivalent vaccines can be used as a single dose, this information may encourage increased vaccine use and coverage in regions with low vaccine uptake, as a simplified vaccination programme relying on a single dose will likely be more acceptable than the current two doses for a primary series. Thus, results from the trial will guide local policy recommendations for the rational use of available vaccines, outside of high-income countries.</address>\n<address>\n We would now like to compare the performance and safety profiles of the Pfizer-BioNTech Omicron-adapted bivalent COVID-19 vaccine, with that of the corresponding original Pfizer-BioNTech vaccine in previously COVID-19 unvaccinated adults in East African adults, to determine whether it induces a bigger immune response, while retaining a similar safety profile. The present trial is planned in Kilifi, Kenya and in Dar es Salaam, Tanzania.</address>\n<address>\n <p>\n  </p>\n <address>\n <p>\n <br />\n <!-- /--></p>\n <p align=\"left\">\n  </p>\n </address>\n <p>\n  </p>\n</address>\n
      • short_titleBiMVaC01
      • protocol_noECCT/23/04/05
      • version_noV.1.0
      • date_of_protocol06-03-2023
      • study_drugBivalent BNT162b2 COVID-19 vaccine
      • disease_conditionCOVID-19
      • product_type_biologicals0
      • product_type_proteins1
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameBivalent BNT162b2
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameOriginal BNT162b2 COVID-19 vaccine
      • comparator_registeredyes
      • comparator_countriesWHO emergency use approval -world wide
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressCGMRCCSC@kemri-wellcome.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantStella Mwakio
      • declaration_date118-04-2023
      • declaration_principal_investigatorProf. Francis Ndungu
      • declaration_date218-04-2023
      • placebo_presentNo
      • study_objectives<p>\n To determine superiority of the immune response against the Omicron BA.4/BA.5 sub lineage of SARS-CoV-2, measured as day 28 neutralising antibodies (Nabs) GMT in previously COVID-19 unvaccinated healthy East African adults following vaccinations with two doses of the Omicron BA.4/BA.5 adapted Bivalent BNT162b2 COVID-19 vaccine (28 days apart), versus two doses of the Original BNT162b2 COVID-19 vaccine.</p>\n<p>\n To determine non-inferiority of the immune response against the Omicron BA.4/BA.5 sublinage of SARS-CoV-2, measured as day 28 NAbs GMT in previously COVID-19 unvaccinated healthy adults following vaccinations with one dose of the Bivalent BNT162b2 COVID-19 vaccine, versus two doses (28 days apart) of the Original BNT162b2 COVID-19 vaccine.</p>\n<p>\n To assess and compare the safety and reactogenicity between the two trial vaccination arms following each of two successive doses of the Bivalent BNT162b2 and the Original BNT162b2vaccines in previously COVID-19 unvaccinated adults.</p>\n
      • principal_inclusion_criteria<p>\n 1) Adult (18 years of age) males, or non-pregnant females.</p>\n<p>\n 2) Able and willing to comply with trial requirements.</p>\n<p>\n 3) For females only, a negative pregnancy test within 24 hours prior to administration of each of the two vaccine doses and willing to take contraception till 28 days after the second vaccine dose.</p>\n<p>\n 4) Provide written informed consent.</p>\n
      • principal_exclusion_criteria<p>\n 1) Documented history of any COVID-19 vaccination.</p>\n<p>\n 2) Prior receipt of an investigational, or licensed vaccine within the last 30 days.</p>\n<p>\n 3) Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the first vaccine dose.</p>\n<p>\n 4) Any confirmed, or suspected immunosuppressive, or immunodeficient state, including HIV infection; asplenia; recurrent severe infections and use of immunosuppressant medication within the past 6 months, except topical steroids or short-term oral steroids (course lasting <14 days).</p>\n<p>\n 5) History of allergic disease, or reactions that could be exacerbated by any component of study vaccine.</p>\n<p>\n 6) Any history of angioedema or anaphylaxis.</p>\n<p>\n 7) Any history of myocarditis and pericarditis.</p>\n<p>\n 8) Pregnancy or lactation at the time of screening</p>\n
      • primary_end_points<p>\n Primary</p>\n<p>\n • Geometric mean titres (GMTs) of Omicron-specific NAbs at 28 days following 2 doses of Bivalent BNT162b2 COVID-19 vaccine and 2 doses of Original BNT162b2COVID-19 vaccine.</p>\n<p>\n Secondary immunogenicity</p>\n<p>\n • GMTs of Omicron specific NAbs at 28 days following 1 dose of Omicroncontaining COVID-19 vaccine and 1 dose of original BNT162b2 monovalent COVID-19 vaccine.</p>\n<p>\n • GMTs of BAbs at 28 days following each dose of bivalent Omicron-containing COVID-19 vaccine and each dose of original BNT162b2 monovalent COVID19 vaccine.</p>\n<p>\n • GMTs of Omicron-specific NAbs at 6 months following last vaccine dose in each treatment arm.</p>\n<p>\n • GMTs of BAbs at 6 months following the last vaccine dose in each treatment arm. • GMTs of NAbs against ancestral strain of SARS-CoV-2 at 28 days following each vaccine dose in each treatment arm.</p>\n<p>\n • GMTs of NAbs against ancestral strain of SARS-CoV-2 at 6 months following last vaccine dose in each treatment arm.</p>\n<p>\n • Geometric mean fold rise (GMFR) of BAbs, Omicron-specific NAb and NABs against ancestral strain of SARS-CoV-2 at</p>\n<p>\n -28 days post dose 1 as compared to baseline titres for each treatment arm.</p>\n<p>\n -28 days post dose 2 as compared to baseline and pre-dose 2 titres for each treatment arm.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence1
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study1
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div ccp_infra_copy_id=\"e22fa8c7-c0eb-4ca0-a3ca-408b47b3bb2d\" ccp_infra_timestamp=\"1681799652268\" ccp_infra_user_hash=\"211019686\" ccp_infra_version=\"3\" data-ccp-timestamp=\"1681799652268\">\n <table style=\"border-collapse: collapse; width: 414pt;\" width=\"552\">\n <colgroup>\n <col style=\"width: 179pt;\" width=\"238\" />\n <col style=\"width: 236pt;\" width=\"314\" />\n </colgroup>\n <tbody>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Principal Investigator (Francis Ndungu)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204); width: 236pt;\" width=\"314\">\n Overal Trial supervision</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Medical officer(Makobu Kimani)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Principal assitant to P.I and head clinical section</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Project Manager (Stella Mwakio)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Day-to-day Project supervision</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Grant manager (Keith Kipoto</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n project accountant </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Clinical officer (Two)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Provide clinical services including vaccine administration </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Nurse (five)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Clinical Services and Emergence care</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Pharmacist (Mwaganyuma Mwatasa)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Vaccine handling management </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Pharmaceutical technologist (Two)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Vaccine prepration (Unblinded)</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Research counselor (one)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n HIV testing and counselling </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Community facilitator (one)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Link between clinical and community teams </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Research officer (Post Doc Entry)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Principal assitant to P.I on immunology work </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Laboratory Technician (two)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Day-to-day sample handling </td>\n </tr>\n <tr height=\"42\" style=\"height: 31.5pt;\">\n <td class=\"xl139\" height=\"42\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 31.5pt;\" width=\"238\">\n Assistant Research officer (Jennifer Musyoki's)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Supervision of lab technitians</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Field Supervisor (Juliana)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Supervision of field teams</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Data Manager (Stanely Cheriot)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Data quality assurance </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Data Clerk (four)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Data entry</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Field Worker (six)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Recruitment of volunteers </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Administrative Assistant (one)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n General administration of the project</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Lab Archivist (One)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Store samples & Maintain sample data</td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Biostatician (Benedict Orinid)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Data analaysis </td>\n </tr>\n <tr height=\"42\" style=\"height: 31.5pt;\">\n <td class=\"xl139\" height=\"42\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 31.5pt;\" width=\"238\">\n Monitors (two: Maureen Gacemba, Siti Ndaa)</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n Internal monitoring of study procedures </td>\n </tr>\n <tr height=\"21\" style=\"height: 15.75pt;\">\n <td class=\"xl139\" height=\"21\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); background: rgb(255, 242, 204); width: 179pt; height: 15.75pt;\" width=\"238\">\n Grants Officer Oxford</td>\n <td class=\"xl109\" style=\"padding-top: 1px; padding-right: 1px; padding-left: 1px; font-size: 11pt; font-family: Calibri, sans-serif; vertical-align: bottom; border-width: 0.5pt; border-style: solid; border-color: rgb(217, 217, 217); white-space: nowrap; background: rgb(255, 242, 204);\">\n post award management</td>\n </tr>\n </tbody>\n </table>\n</div>\n<p>\n <strong>Site Facility</strong></p>\n<p>\n Clinical Trial facility located within the KEMRI-CGMRC Kilifi is well equiped with Offices for Clinical Trials Staff and Principal investiagtors.</p>\n<p>\n It is well equiped with Resources and personnel for Data management, clinical trial laboartory, clinical trial Phamacy and the Clinical areas.</p>\n<p>\n <strong>Emergency Preparedness</strong></p>\n<p>\n <span class=\"ui-provider gz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Individual vaccinees will be closely monitored for symptoms and signs including chest pain, fatigue, swelling of the legs, ankles and feet, unexplained shortness of breath, light-headedness and flu-like symptoms during the 30 minutes following each vaccination at the clinic and will be monitored closely by the study staff via daily phone calls for the subsequent 7 days for such occurrences. KEMRI-CGMR-C has the capacity to diagnose and refer such cases to specialists like the Kilifi County, and the Aga Khan and Premier Hospitals at the coast of Kenya</span></p>\n
      • other_details_explanation<p>\n <span class=\"ui-provider gz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">The sponsor (Oxford University), has sub-contracted the KWTRP as one of two sites to conduct the study. There currently is no data on the bivalent vaccine in African populations. The vaccine manufacturer (Pfizer), will soon discontinue production of the original monovalent vaccine. Consequently, it is imperative that data on the bivalent vaccine from African populations are availed.</span></p>\n
      • other_details_regulatory_notapproved<p>\n TMDA TANZANIA</p>\n
      • other_details_regulatory_approved<p>\n None</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n none</p>\n
      • estimated_duration16months
      • 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_comparatorstandard of care arm
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI-CGMRC Kilifi
      • single_site_physical_address230
      • single_site_contact_personKimani Makobu
      • single_site_telephone+254722258102
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states2
      • number_of_sites
      • multi_country_listKenya \nTanzania
      • data_monitoring_committeeYes
      • total_enrolment_per_site290 each site
      • total_participants_worldwide580
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameMac
      • investigator1_middle_nameMakobu
      • investigator1_family_nameKimani
      • investigator1_qualificationMBChB
      • investigator1_professional_address230
      • investigator1_telephone+254722258102
      • investigator1_emailKMakobu@kemri-wellcome.org
      • organisations_transferred_No
      • number_participants580
      • notification<p>\n None</p>\n
      • approval_date06-07-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted06-07-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe reviewer comments have been addressed.
      • final_report<p>\n This was a phase 3 multicounty, randomized controlled, double blind, trial is with two arms</p>\n<p>\n -  arm 1: randomized to receive the monovalent Pfizer COVID-19 vaccine; optimized for the ancestral Wuhan strain of SARS-CoV-2. Containing 30µg of the S protein from the ancestral Wuhan-Hu-1 strain </p>\n<p>\n -  arm 2: randomized to receive the bivalent Pfizer vaccine; optimized against the Omicron BA4/5 and Wuhan strains of SARS-CoV-2. mRNA vaccine containing 15/15 µg (each) of the S-protein from the ancestral strain & Omicron BA.4/BA.5 sub-lineages.</p>\n<p>\n The study was designed to demonstrate the non-inferiority of the Bivalent vaccine compared to the monovalent one. Non-inferiority was compared for safety, reactogenicity and immunogenicity.</p>\n<p>\n Participants were randomized in a 1:1 ration to either study arm. They each received two (2) doses of either vaccine. The dosing schedules were identical (28 days apart).</p>\n<p>\n Two hundred and ninety (290) were enrolled from the Kilifi Health and Demographic Surveillance System (HDSS). Enrollment began on 26^th September 2023 and the last participant received their last vaccine dose on 29^th December 2023.</p>\n<p>\n There was one withdrawal just prior to administration of the second vaccine dose. The participant opted not to have the vaccine administered out of personal choice. He did not exit the study, however.  There were also four (4) participants who were lost to follow-up despite all efforts to locate them. One of the participants is in legal custody while three moved outside the study area for work. The last participant last visit (LPLV) was on the 31^st of August 2024.  Participants made a total of seven study visits including screening, enrollment, vaccination, safety and reactogenicity visits, booster vaccination visit, repeat safety, immunogenicty and reactogenicity visits. Additionally, study staff had virtual contact with participants in the seven days following a vaccination visit. </p>\n<p>\n Safety profile of both vaccine regimens was evaluated through the collection and reporting of both solicited and unsolicited adverse reaction in the three months subsequent to administration of the investigational products. Information and follow-up for serious adverse events (SAE’s) was collected for the entire duration of a participant’s study involvement.</p>\n<p>\n There were two SAEs at the Kenyan site and a SUSAR (resulting in death of a participant), reported at the Tanzanian site. Neither the SAEs nor the SUSAR were related to study procedures or participation. All safety reports were submitted to the respective ethical and regulatory authorities as well as the DSMB.</p>\n<p>\n There was one substantive protocol amendment made in May 2024. The amendment sought to set up an additional cohort that would receive a vaccine optimized against the Omicron XBB 1.5 variant of SARS-CoV-2. However, this arm of the study did not proceed as the funder opted not to continue with that study arm.  The the declaration by WHO that COVID-19 was no longer a public health emergency of international concern, informed the decision by the funder.  There was one pregnancy reported and resulted in a positive outcome with a healthy child delivered with no congenital anomalies.</p>\n<p>\n The data safety monitoring board (DSMB) had three meetings and recommended the study procced without any changes.</p>\n<p>\n All protocol deviations and violation that occurred in the study were reported and uploaded onto the PPB portal. Response letters were received from SERU for all reported protocol deviations /violation.</p>\n<p>\n In conclusion, both the original monovalent and the bivalent studied vaccine were well tolerated. Preliminary data point to a robust humoral immune response against the vaccine antigens. Unblinded data will soon be available to compare the immune responses of each vaccine</p>\n
      • implication_results<p>\n <span data-teams=\"true\">The safety profile for both vaccines is comparable. There were no safety signals in the entire cohort. As soon as immunogenicity data are available we will update on the impact to policy around vaccination against COVID-19. </span></p>\n
      • quantity_imported500 BNT162B2 Monovalent,687 BNT162b2 Bivalent,250 XBB1.5
      • quantity_dispensed293 Monovalent,288 Bivalent ,0 XXB
      • quantity_destroyedAwaiting Feedback from the PPB Inspector
      • quantity_exported0
      • balance_site207 Monovalent,399 bivalent and 250 XBB
      • final_date0000-00-00
      • modified2025-03-21 23:37:55
      • created2023-04-14 11:56:10
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id925
        • application_id1257
        • given_nameNDUNGU
        • middle_name
        • family_nameFRANCIS
        • qualificationPh.D.in immunology
        • professional_address230
        • telephone+254715279268
        • emailFNdungu@kemri-wellcome.org
        • created2023-04-14 14:02:21
        • modified2023-07-06 12:01:13
      • 1(array)
        • id926
        • application_id1257
        • given_nameSaid
        • middle_name
        • family_nameJongo
        • qualificationMMed,PHD
        • professional_address78373
        • telephone+255714939831
        • emailSaid Jongo <sjongo@ihi.or.tz>
        • created2023-04-18 08:21:23
        • modified2023-07-06 12:01:13
    • SiteDetail(array)
      • 0(array)
        • id1486
        • application_id1257
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2023-04-14 14:02:21
        • modified2023-07-06 12:01:13
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id660
        • application_id1257
        • sponsorUniversity of Oxford
        • sponsor_typeResearch Institution
        • contact_personProf. Phillip Bejon
        • address230
        • telephone_number+254 709 983 549
        • fax_number
        • cell_number+254 709 983 549
        • email_addresspbejon@kemri-wellcome.org
        • created2023-04-14 14:02:21
        • modified2023-07-06 12:01:13
  • 4(array)
    • Application(array)
      • id982
      • user_id32
      • trial_status_id1
      • abstract_of_study<p>\n L-arginine is an essential amino acid in pregnancy and a key mediator of placental development and function. In many low-resource settings, widespread protein undernutrition contributes to L-arginine deficiency in pregnancy which is associated with an increased risk of adverse pregnancy outcomes. Using a preclinical model, we have previously shown that dietary L-arginine supplementation enhances placental vascular development and improves pregnancy outcomes. L-citrulline is an amino acid that is efficiently converted to L-arginine in the body and has a more palatable flavour profile.</p>\n<p>\n PRIMARY OBJECTIVE: To determine if daily antenatal oral supplementation with L-citrulline can reduce adverse pregnancy outcomes (defined as a composite of fetal loss, infants born preterm, small for gestational age or with low birthweight) among pregnant women at high risk of malaria and protein undernutrition in Kenya.</p>\n<p>\n OVERVIEW OF STUDY DESIGN: This is an individually randomized, two-arm, parallel-group, placebo-controlled clinical trial involving 2,960 pregnant women randomly assigned (1:1) to one of two study arms: i) L-citrulline arm –twice daily 6.0 g sachet, each containing 5.00 g of quality-assured L-citrulline powder, 0.66 g maltodextrin and 0.30 g lactose anhydrous, 0.03 g citric acid, 0.01 g lemon flavour + antenatal standard of care with enhanced monitoring (n=1,480); or ii) Placebo arm: 6.0 g sachet of quality-assured placebo, each consisting of 3.6 g maltodextrin and 2.4 g lactose monohydrate, 0.03 g citric acid, 0.01 g lemon flavour + antenatal standard of care with enhanced monitoring (n=1,480). All participants will continue to take the assigned product for 6 weeks after delivery and will receive an enhanced antenatal standard of care. The primary outcome is the clinical composite ‘adverse pregnancy outcome’. Secondary outcomes include longitudinal assessments of physiological and molecular markers of endothelial function, angiogenesis, inflammation, placental function, L-arginine metabolism, neonatal sepsis, mortality, and early childhood neurocognitive development to age 24 months. The effect of L-citrulline supplementation on the composition of the participants’ vaginal microbiota and the intestinal microbiota of both the participants and their newborns will be analysed in a subset of 132 mother/infant dyads. All maternal participants of the AGREE trial will be followed for 6 weeks post-partum and the children will be followed until age 2 years. Written informed consent will be obtained.</p>\n
      • study_title<div>\n Oral antenatal L-citrulline supplementation to reduce adverse pregnancy outcomes: a two-arm, randomized, placebo-controlled multi-site trial in Kenya</div>\n
      • laymans_summary<p>\n STUDY AIMS AND OBJECTIVES: The goal of the AGREE trial is to test whether a dietary supplement containing a common food component, an amino acid called L-citrulline, can help pregnant Kenyan women at risk of malaria have healthier pregnancies and healthier babies.</p>\n<p>\n METHODS: 2,960 pregnant Kenyan women will be enrolled and randomly assigned to take either a twice daily dietary supplement containing L-citrulline or a placebo supplement without additional L-citrulline. The intervention consists of sachets containing a powder formulation of either L-citrulline or a matching placebo that is nearly tasteless and can easily be mixed with food or added to drinks. Maternal participants will be seen every month until delivery and at weeks 1 and 6 after birth. The newborns will be seen at birth, around 1 and 6 weeks after birth, and then at ages 6, 12, 18, and 24 months. The main outcome of the study is ‘adverse pregnancy outcome’, which includes loss of the baby (miscarriage or stillbirth), or if the baby is born too early or too small. The study will monitor factors in the mother’s blood that indicate how well the placenta and mother’s blood vessels are working, how much inflammation is in her body, and how her body is using L-citrulline and its impact on her breastmilk. The researchers will also examine the effect of the supplements on the baby’s survival after birth, the bacterial flora of the mother’s vagina and in her and her baby’s gut (microbiome), the impact of COVID-19 on the effect of nutritional supplements, and the child’s neurologic development in the first two years of life.</p>\n<p>\n POTENTIAL APPLICATIONS AND BENEFITS: There are few safe, effective, and affordable interventions to improve pregnancy outcomes in low resource settings where the highest rates of poor birth outcomes occur. L-citrulline is naturally found in many foods and is changed into another important amino acid, L-arginine, in the body. L-arginine is important for the growth of a healthy placenta and healthy baby. Adding L-citrulline to the diets of pregnant women may be an effective and affordable way to improve the health of their babies. The results of the AGREE trial could help to guide obstetric and public health policy and provide a sustainable solution that could be implemented at the community level.</p>\n
      • short_titleAGREE
      • protocol_noECCT/23/04/04
      • version_no3.0
      • date_of_protocol30-09-2022
      • study_drugL-citrulline
      • disease_conditionPregnancy; Malaria; Nutrition; placental development; preterm birth, fetal growth restriction
      • product_type_biologicals1
      • product_type_proteins1
      • product_type_immunologicals0
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      • comparatorNo
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      • email_addresstonysangke@gmail.com
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      • declaration_applicantDr. Ruth Njoroge
      • declaration_date117-04-2023
      • declaration_principal_investigatorDr. Hellen Barsosio
      • declaration_date217-04-2023
      • placebo_presentYes
      • study_objectives<div>\n The overall aim of the study is to provide definitive evidence that twice daily oral antenatal supplementation with L-citrulline is a viable strategy to reduce adverse pregnancy outcomes among pregnant women living in areas with high rates of undernutrition and malaria transmission in sub-Saharan Africa.</div>\n<div>\n  </div>\n<div>\n Primary objective</div>\n<div>\n To determine if twice daily antenatal oral supplementation with 5 g L-citrulline can reduce adverse pregnancy outcomes (defined as a composite of fetal loss, infants born small for gestational age (SGA) or with low birth weight (LBW), or preterm birth) among pregnant women at high risk of malaria and protein undernutrition in Kenya.</div>\n<div>\n  </div>\n<div>\n Secondary objectives</div>\n<div>\n 1. To determine the efficacy of twice daily oral antenatal L-citrulline supplementation on:</div>\n<div>\n • L-arginine bioavailability and nitric oxide biogenesis, as indicated by maternal and umbilical cord plasma concentrations of key circulating markers including L-arginine, ADMA, SDMA.</div>\n<div>\n • pregnancy outcomes such as the individual components of the primary composite outcome, as well as preterm premature rupture of membranes (PPROM), pre-eclampsia or eclampsia, and mean newborn birthweight, gestational age, weight-for-gestational age, and maternal haemoglobin at delivery</div>\n<div>\n • maternal and umbilical cord blood circulating markers of endothelial function, angiogenesis, inflammation, intestinal barrier function, and placental function</div>\n<div>\n • maternal physiological indicators of endothelial function including blood pressure, peripheral vascular function, and proteinuria</div>\n<div>\n • Vertical transmission of infections, including SARS-CoV-2, across the placenta to the fetus</div>\n<div>\n • The microbial diversity richness and abundance in the maternal vaginal microbiota and maternal + newborn intestinal microbiota, and nutritional and microbial composition of breast milk</div>\n<div>\n • Neonatal sepsis and mortality up to 6 weeks of age</div>\n<div>\n • Early childhood neurocognitive development up to 2 years of age</div>\n<div>\n 2. To determine the safety and tolerability of twice daily antenatal oral supplementation with L-citrulline by monitoring adverse supplement reactions and adverse/severe adverse events.</div>\n
      • principal_inclusion_criteria<p>\n Pregnant women aged 16-40 years, inclusive to 24 weeks gestational age as confirmed by ultrasound, who have a viable singleton pregnancy, are residents of the study area, willing to adhere to scheduled and unscheduled study visit procedures, and willing to deliver in a study clinic or hospital</p>\n
      • principal_exclusion_criteria<p>\n Includes: multiple pregnancies (i.e. twin/triplets); pre-existing hypertension, renal disease and/or diabetes, or severe anaemia (Hb < 5 g/dL); HIV-positive or HIV status unknown; malformations or nonviable pregnancy observed on enrolment ultrasound; known allergy or contraindication to any of the study supplements including lactose intolerance and/or observing a lactose-free diet ; unable to give consent; or concurrent participation in any other clinical trial</p>\n
      • primary_end_points<p>\n The primary outcome is ‘adverse pregnancy outcome’ defined as a composite of fetal loss (spontaneous abortion or stillbirth), singleton live births born SGA or with LBW, or preterm birth (PTB). ‘Small for gestational age’ will be defined using the INTERGROWTH population reference’s 10th percentile.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
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      • trial_other0
      • trial_other_specify
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      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div>\n The study will be conducted in Kisumu and Busia for a start and later expand to Siaya county. Each of these towns has a county paediatric ward on which this study will be based, and the adjacent facilities will act as satellite sites for recruitment and referral. </div>\n<div>\n  </div>\n<div>\n The key study staff will include the following:</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Chief Investigator – Prof Feiko ter Kuile, MD, PhD1,2</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Co-PI - Dr Hellen Barsosio, MD, MSc (Kenya)</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Co-PI - Dr Kevin Kain, MD (Canada)</div>\n<div>\n •<span style=\"white-space:pre\"> </span>CO-Investigator- Dr Simon Kariuki, PhD2</div>\n<div>\n •<span style=\"white-space:pre\"> </span>CO-Investigator- Dr Chloe McDonald, MSc, PhD</div>\n<div>\n •<span style=\"white-space:pre\"> </span>CO-Investigator- Dr Julie Wright, MD, MSc</div>\n<div>\n •<span style=\"white-space:pre\"> </span>CO-Investigator- Prof Maia Lesosky, PhD</div>\n<div>\n •<span style=\"white-space:pre\"> </span>CO-Investigator- Ms Evelyne Delylah Ondieki, MSc</div>\n<div>\n •<span style=\"white-space:pre\"> </span>CO-Investigator- Mr Kephas Otieno, M</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Pharmacist - Dr Ruth Njoroge, BPharm</div>\n<div>\n  </div>\n<div>\n Additionally, each of the sites will have the following personnel:</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Clinical Officers - 3</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Lab Technicians/ Phlebotomist -1</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Field workers- 5</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Data Officers -1</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Data clerks-1</div>\n<div>\n •<span style=\"white-space:pre\"> </span>QA/QC officers -1</div>\n<div>\n  </div>\n<div>\n Site capacity</div>\n<div>\n All the sites have the required capacity to conduct clinical trials. In addition, these sites are also KEMRI/CDC research sites in which we have invested in capacity development, infrastructure and have existing Memorandum of Understanding (MoUs) over the years.</div>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n N/A</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration60 months
      • 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 for L-citrulline
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
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      • multiple_sites_member_stateYes
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites3
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site2,960 (1,480 per arm)
      • total_participants_worldwide2,960 (1,480 per arm)
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionNo
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      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameFeiko
      • investigator1_middle_nameter
      • investigator1_family_nameKuile
      • investigator1_qualificationMD, PhD
      • investigator1_professional_addressLiverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
      • investigator1_telephone+254 (0)708 739 228
      • investigator1_emailfeiko.terkuile@lstmed.ac.uk
      • organisations_transferred_No
      • number_participants2,960 (1,480 per arm)
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      • approval_date24-08-2023
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      • date_submitted17-04-2023
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      • modified2025-01-09 15:28:54
      • created2021-03-02 11:06:44
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        • emailhellen.barsosio@lstmed.ac.uk
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