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      • abstract_of_study<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td>\n <p>\n Full title</p>\n </td>\n <td>\n <p>\n Implementation of WHO recommendations for drugs and approaches to prevent and treat postpartum hemorrhage: a multi-country feasibility, acceptability and cost-effectiveness study</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Short title</p>\n </td>\n <td>\n <p>\n AMPLI-PPHI implementation research protocol</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Countries</p>\n </td>\n <td>\n <p>\n Democratic Republic of the Congo, Guinea, India, Kenya    </p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Timeline</p>\n </td>\n <td>\n <p>\n 24 months (anticipated January 2024 – December 2025)</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Goal</p>\n </td>\n <td>\n <p>\n To generate evidence on the feasibility, acceptability and cost-effectiveness of expanding the package of drugs and approaches available to implement WHO recommendations for postpartum hemorrhage prevention and treatment in high-burden countries</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Research objectives</p>\n </td>\n <td>\n <ol>\n <li>\n Assess the feasibility and acceptability of advance distribution of misoprostol for self-administration to prevent postpartum hemorrhage at births outside of health facilities in selected project sites;</li>\n </ol>\n <p style=\"margin-left:14.4pt;\">\n  </p>\n <ol>\n <li value=\"2\">\n Assess the feasibility and acceptability of introducing heat-stable carbetocin for postpartum hemorrhage prevention and tranexamic acid for postpartum hemorrhage treatment at health centers and hospitals in selected project sites;</li>\n </ol>\n <p style=\"margin-left:14.4pt;\">\n  </p>\n <ol>\n <li value=\"3\">\n Assess the cost-effectiveness of the combined implementation of advance distribution of misoprostol for self-administration to prevent postpartum hemorrhage at births outside of health facilities, as well as heat-stable carbetocin for postpartum hemorrhage prevention and tranexamic acid for postpartum hemorrhage treatment at health facilities; and</li>\n </ol>\n <p>\n  </p>\n <ol>\n <li value=\"4\">\n Examine how and why barriers and enablers to expanding the package of drugs and approaches for postpartum hemorrhage prevention and treatment vary within and across selected project sites in four countries.</li>\n </ol>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Methods</p>\n </td>\n <td>\n <p style=\"margin-left:-.9pt;\">\n The proposed study is a multi-country mixed-methods implementation research study. Convergent qualitative and quantitative methods will be used to address each objective. For objectives 1 and 2, the feasibility and acceptability of expanding the package of drugs and approaches available to prevent and treat postpartum hemorrhage in each study site will be assessed through secondary analysis of routine health service statistics and program documentation, complemented by primary qualitative data collection to capture the experiences and perspectives of those involved in the introduction and operationalization of updated PPH prevention and treatment protocols. For objective 3, an economic evaluation will be conducted to determine the incremental cost-effectiveness of an expanded package of PPH drugs and approaches compared with the current standard of care for PPH prevention and treatment in each country.  For objective 4, within and cross-country variation in barriers and enablers to expanding the package of drugs and approaches for PPH prevention and treatment will be explored through secondary analysis of program documentation, complemented by primary qualitative data collection at the community, facility and health system levels.</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Expected Outcomes</p>\n </td>\n <td>\n <p>\n AMPLI-PPHI will support Ministries of Health in each country to use study findings to update national policies/guidelines/protocols (where applicable) and catalyze adoption of WHO-recommendations for PPH prevention and treatment.  Study findings will also be disseminated through learning exchanges organized with the Ministry of Health, health professional associations and other stakeholders in neighboring countries to accelerate adoption of recommendations and translation of policies into practice. Wider dissemination of findings will be done through scientific meetings or conferences as well as publications in peer reviewed journals, and aim to inform iterative updates of WHO guidance relating to PPH as well as investments in addressing bottlenecks in implementing evidence-based interventions to address maternal mortality and morbidity.</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • study_title<p>\n Implementation of WHO recommendations for drugs and approaches to prevent and treat postpartum hemorrhage: a multi-country feasibility, acceptability and cost-effectiveness study</p>\n
      • laymans_summary<div>\n Jhpiego through the Accelerating Measurable Progress and Leveraging Investments for Postpartum Hemorrhage Impact (AMPLI_PPHI) project in collaboration with Division of reproductive and maternal health and Makueni county (department of health) plans to carry out a multi-country study to assess implementation of WHO recommendations for drugs and approaches to prevent and treat postpartum hemorrhage.</div>\n<div>\n The purpose of this study is to assess feasibility and acceptability of expanding the package of drugs and approaches available to prevent and treat postpartum hemorrhage in 36 select health facilities in Makueni county. The study participants will involve postpartum women, community representatives, healthcare providers and key MNH stakeholders who have been consented to be in the study. An inclusion and exclusion criteria will be used to determine the eligibility of the study participants.</div>\n<div>\n The findings from this study will be used inform government decisions on where and how to introduce an expanded package of WHO-recommended drugs and approaches for PPH prevention and treatment. Study participants and people living in study locations may benefit from improved health services if study findings stimulate policy change and resource allocation. Research findings are also intended to inform WHO guidance on operationalizing PPH-related recommendations</div>\n
      • short_titleAP Implementation Research
      • protocol_noECCT/24/01/02
      • version_no2
      • date_of_protocol27-09-2023
      • study_drug1. Heat-stable carbetocin (Carbetocin Ferring), 2. Tranexamic Acid (TEXAKIND) and 3. Misoprostol(MISOCLEAR)
      • disease_conditionPost-partum Haemorrhage
      • 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_name1. Carbetocin Ferring, 2. Texakind and 3. Misoclear
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresschristine.muia@jhpiego.org
      • applicant_covering_letter1
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      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum0
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      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
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      • applicant_hard_copies(null)
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      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicant0708822611
      • declaration_date121-12-2023
      • declaration_principal_investigatorDr. Daisy Ruto
      • declaration_date222-12-2023
      • placebo_presentNo
      • study_objectives<p>\n General objective</p>\n<p>\n The general objective is to <strong>generate evidence on the feasibility, acceptability and cost-effectiveness of expanding the package of drugs and approaches available to implement WHO recommendations for PPH prevention and treatment</strong> in selected high-burden countries.</p>\n<p>\n  </p>\n<p>\n Specific objectives</p>\n<ol>\n <li>\n Assess the feasibility and acceptability of advance distribution of misoprostol for self-administration to prevent PPH at births outside of health facilities in selected project sites;</li>\n <li>\n Assess the feasibility and acceptability of introducing heat-stable carbetocin (HSC) for PPH prevention and tranexamic acid (TXA) for PPH treatment at health centers and hospitals in selected project sites;</li>\n <li>\n Assess the cost-effectiveness of the combined implementation of advance distribution of misoprostol for self-administration to prevent PPH at births outside of health facilities, as well as HSC for PPH prevention and TXA for PPH treatment at health facilities; and</li>\n <li>\n Examine how and why barriers and enablers to expanding the package of drugs and approaches for PPH prevention and treatment vary within and across selected project sites in four countries</li>\n</ol>\n
      • principal_inclusion_criteria<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td>\n <p>\n <strong>Data collection tool</strong></p>\n </td>\n <td>\n <p>\n <strong> Inclusion criteria</strong></p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Tool 1</strong>: Key informant interview guide for ANC providers involved in advance distribution of misoprostol for PPH prevention</p>\n </td>\n <td>\n <ul>\n <li>\n ANC providers at facilities supporting advance distribution of misoprostol for PPH prevention</li>\n <li>\n In role for at least 3 months</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Tool 2:</strong> Focus group discussion guide for community health workers in areas targeted for advanced distribution of misoprostol for PPH prevention</p>\n </td>\n <td>\n <ul>\n <li>\n Community health workers in catchment area of facilities supporting advance distribution of misoprostol for PPH prevention</li>\n <li>\n In role for at least 3 months</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Tool 3:</strong> Key informant interview guide for community leaders and organizations in areas targeted for advance distribution of misoprostol for PPH prevention</p>\n </td>\n <td>\n <ul>\n <li>\n Community leaders identified by local authorities or community health workers</li>\n </ul>\n <p style=\"margin-left:7.0pt;\">\n OR</p>\n <ul>\n <li>\n Representatives of civil society organization collaborating with the AMPLI-PPHI project</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Tool 4:</strong> In-depth interview guide for women who received advance distribution of misoprostol for PPH prevention</p>\n </td>\n <td>\n <ul>\n <li>\n Postpartum women aged 18+ who received advance distribution of misoprostol to prevent PPH</li>\n <li>\n Gave birth within 2 months prior to data collection</li>\n <li>\n Are willing to be contacted by study team members</li>\n <li>\n No apparent cognitive disabilities (able to personally provide informed consent)</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Tool 5:</strong> Structured survey for maternity care providers at facilities introducing heat-stable carbetocin for PPH prevention and/or tranexamic acid for PPH treatment</p>\n </td>\n <td>\n <ul>\n <li>\n Skilled health personnel responsible for labor & delivery care at facilities using HSC and/or TXA</li>\n <li>\n In role for at least 3 months</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Tool 6:</strong> Key informant interview guide for maternity care providers at facilities introducing heat-stable carbetocin for PPH prevention and/or tranexamic acid for PPH treatment</p>\n </td>\n <td>\n <ul>\n <li>\n Skilled health personnel responsible for labor & delivery care at facilities using HSC and/or TXA</li>\n <li>\n In role for at least 3 months</li>\n </ul>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Tool 7:</strong> Key informant interview guide for health facility management</p>\n </td>\n <td>\n <ul>\n <li>\n Officer in-charge of health facility (e.g., hospital director, head of health center) OR in-charge of ANC and/or maternity unit at project-supported facility</li>\n <li>\n In role for at least 3 months</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Tool 8:</strong> Key informant interview guide for national and sub-national policymakers and other project stakeholders</p>\n </td>\n <td>\n <ul>\n <li>\n Stakeholder with a position of responsibility related to maternal health, regulatory and/or procurement of PPH drugs, and/or programming</li>\n <li>\n In role, or related role, for at least 3 months</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • principal_exclusion_criteria<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td>\n <p>\n <strong>Data collection tool</strong></p>\n </td>\n <td>\n <p>\n <strong>Exclusion criteria</strong></p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Tool 1</strong>: Key informant interview guide for ANC providers involved in advance distribution of misoprostol for PPH prevention</p>\n </td>\n <td>\n <ul>\n <li>\n Students, interns or temporary staff at project-supported facilities</li>\n </ul>\n <ul>\n <li>\n ANC providers working at facility less than 3 months</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Tool 2:</strong> Focus group discussion guide for community health workers in areas targeted for advanced distribution of misoprostol for PPH prevention</p>\n </td>\n <td>\n <ul>\n <li>\n Community health workers in role less than 3 months</li>\n </ul>\n <ul>\n <li>\n Community health workers residing outside of the catchment areas of project-supported facilities for advance distribution of misoprostol for PPH prevention</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Tool 3:</strong> Key informant interview guide for community leaders and organizations in areas targeted for advance distribution of misoprostol for PPH prevention</p>\n </td>\n <td>\n <ul>\n <li>\n Community leaders and organization representatives outside of catchment areas of facilities selected to be demonstration sites for advance distribution of misoprostol for PPH prevention</li>\n </ul>\n <ul>\n <li>\n Individuals under age 18</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Tool 4:</strong> In-depth interview guide for women who received advance distribution of misoprostol for PPH prevention</p>\n </td>\n <td>\n <ul>\n <li>\n Postpartum women under age 18</li>\n <li>\n Women who did not receive advance distribution of misoprostol for PPH prevention</li>\n <li>\n Women who gave birth more than 2 months prior to data collection</li>\n <li>\n Women recently experiencing stillbirth or newborn death; women with severely ill infant</li>\n </ul>\n <ul>\n <li>\n Women unable to provide informed consent</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Tool 5:</strong> Structured survey for maternity care providers at facilities introducing heat-stable carbetocin for PPH prevention and/or tranexamic acid for PPH treatment</p>\n </td>\n <td>\n <ul>\n <li>\n Students, interns or temporary staff at project-supported facilities for HSC and/or TXA</li>\n </ul>\n <ul>\n <li>\n Maternity care providers working at facility less than 3 months</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Tool 6:</strong> Key informant interview guide for maternity care providers at facilities introducing heat-stable carbetocin for PPH prevention and/or tranexamic acid for PPH treatment</p>\n </td>\n <td>\n <ul>\n <li>\n Students, interns or temporary staff at facilities selected as demonstration sites</li>\n <li>\n Maternity care providers working at facility less than 3 months</li>\n </ul>\n <ul>\n <li>\n Facility, ANC and/or maternity ward in-charges</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Tool 7:</strong> Key informant interview guide for health facility management</p>\n </td>\n <td>\n <ul>\n <li>\n In role at facility less than 3 months</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n <strong>Tool 8:</strong> Key informant interview guide for national and sub-national policymakers and other project stakeholders</p>\n </td>\n <td>\n <ul>\n <li>\n In role less than 3 months</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • primary_end_points<p>\n Study findings related to feasibility and acceptability of expanding the package of drugs and approaches available for PPH prevention and treatment, as well as barriers and facilitators to implementation in different settings, will be used for iterative learning and adaptation of AMPLI-PPHI activities over the life of the project. Learning will be made available to national and sub-national decision-makers, health professional associations, community actors and participants.</p>\n<p>\n AMPLI-PPHI will support Ministry of Health to use study findings to update national policies/guidelines/protocols (where applicable) and catalyze adoption of WHO-recommendations for PPH prevention and treatment.  Study findings will also be disseminated through learning exchanges organized with the Ministry of Health, health professional associations and other stakeholders in neighboring countries to accelerate adoption of recommendations and translation of policies into practice. Wider dissemination of findings will be done through scientific meetings or conferences as well as publications in peer reviewed journals and aim to inform iterative updates of WHO guidance relating to PPH as well as investments in addressing bottlenecks in implementing evidence-based interventions to address maternal mortality and morbidity</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyThe study is an implementation research, focusing on feasibility, acceptability and cost-effectives on implementing WHO recommendations on PPH prevention and treatment medicines.
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyThe study is an implementation research, focusing on feasibility, acceptability and cost-effectives on implementing WHO recommendations on PPH prevention and treatment medicines.
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <thead>\n <tr>\n <th>\n <p>\n <strong>Study Team Member</strong></p>\n </th>\n <th>\n <p>\n <strong>Roles/Responsibilities</strong></p>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td>\n <p>\n Daisy Ruto, MMD Obs/Gyn, MBChB<strong> (Principal investigator) </strong></p>\n </td>\n <td>\n <p>\n AMPLI-PPHI Kenya Technical Advisor; <em><u>Responsibilities</u></em>: Contribute to study design; in Kenya provide leadership for all research activities and ensure compliance with study protocols, related SOPs and relevant policies (e.g., donor, IRB, government); manage study tool piloting, training of data collectors and oversee day-to-day study management, quality assurance; and data management and analysis; lead interpretation of findings; support dissemination of findings. Manage localIRB correspondence and requirements.  She will provide overall technical guidance and clinical advice on research related activities during implementation of the study. Responsible for sharing technical updates that reflect latest global guidance on PPH leading to improved knowledge among team members in the area of PPH. She will support team to conceptualize and write publications, articles, abstracts and presentations. She will support the national stakeholder meetings</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\">\n <p>\n <strong>Co-Investigators </strong></p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Christine Muia, MSc (c), BS</p>\n </td>\n <td>\n <p>\n AMPLI-PPHI Kenya Program Manager; <em><u>Responsibilities</u></em>: Contribute to the study design, tools and protocol development, manage study tools piloting, training of data collectors, day-to-day study management, quality assurance and ensuring compliance with study protocol and local IRB correspondence</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Christina Maly, MPH, BA</p>\n </td>\n <td>\n <p>\n Senior Technical Advisor (Monitoring, Evaluation, Research & Learning). <em><u>Responsibilities</u></em>: Provide overall technical leadership for the study design, including protocol and tool development, data collector training, data analysis and interpretation and dissemination of results, overall quality assurance and compliance with JHU, WHO and in-country IRB procedures.</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Doris Mbithi, MMed, MBChB</p>\n </td>\n <td>\n <p>\n Makueni County Department of Health County Obstetrician/ Gynecologist; <em><u>Responsibilities</u></em>: Contribute to the study design, tools and protocol development, offer technical leadership in the implementation of the study, day-to-day study implementation, lead in dissemination of findings at county level, quality assurance and ensure compliance with study protocol including government IRB policies and procedures.</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Edward Serem, MMed, MBChB</p>\n </td>\n <td>\n <p>\n Ministry of Health Division of Reproductive and Maternal Health Unit Head <em><u>Responsibilities</u></em>: Support the study design, tools and protocol development, offer technical leadership in the implementation of the study, contribute to the study interpretation of findings, support dissemination of the findings and day-to-day study implementation to ensure compliance with study protocol including government IRB policies and procedures.</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Elly Odongo, MMed, MBChB</p>\n </td>\n <td>\n <p>\n Kenya Obstetrical and Gynecological Society President Emeritus: <em><u>Responsibilities</u></em>: Contribute to the study design, tools and protocol development, offer technical leadership in the implementation of the study, day-to-day study implementation, support dissemination of findings, quality assurance and ensure compliance with study protocol including government IRB policies and procedures.</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Freda Nyaga, MA (c), BSC</p>\n </td>\n <td>\n <p>\n AMPLI-PPHI Kenya Monitoring, Evaluation & Research Manager; <em><u>Responsibilities: </u></em></p>\n <p>\n Contribute to the study design, tools and protocol development, manage study tools piloting, training of data collectors, data management, day-to-day study management, quality assurance and compliance with study protocol including government IRB policies and procedures</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:108px;height:20px;\">\n <p>\n Hannah Tappis DrPH, MPH, BA</p>\n </td>\n <td style=\"width:516px;height:20px;\">\n <p>\n AMPLI-PPHI Senior Technical Advisor (Research); <em><u>Responsibilities: </u></em></p>\n <p>\n Provide technical and methodology guidance in study design and implementation, including protocol and tool development, SOP establishment, data collector training, data management, data analysis and interpretation and publication of results, support country study leads and co-investigators in research methods; support PI in overall quality assurance and compliance with JHU, WHO and in-country IRB procedures</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:108px;height:20px;\">\n <p>\n <strong>Jim Kelly Mugambi, BSN</strong></p>\n </td>\n <td style=\"width:516px;height:20px;\">\n <p>\n <strong>AMPLI-PPHI Kenya Technical Officer; Responsibilities:  Contribute to the KEMRI protocol review, manage study tools piloting, support training of data collectors, offer technical support on the study implementation, day-to-day study management, quality assurance and ensuring compliance with study protocol</strong></p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Mary Muthengi, MSN, BSN</p>\n </td>\n <td>\n <p>\n AMPLI-PPHI Kenya Technical Officer; <em><u>Responsibilities</u></em>: Contribute to the study design, tools and protocol development, manage study tools piloting, training of data collectors, offer technical support on the study implementation, day-to-day study management, quality assurance and ensuring compliance with study protocol</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Morris Kiio, BSC</p>\n </td>\n <td>\n <p>\n AMPLI-PPHI Kenya Data Analyst; <em>Responsibilities:</em> Contribute to the study design, tools and protocol development, manage study tools piloting, training of data collectors, data management, day to day study management, quality assurance, data analysis and ensuring compliance with study protocol and all agencies including government IRB policies and procedures.</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Michael Muthamia, MSc (c), BSN</p>\n </td>\n <td>\n <p>\n AMPLI-PPHI Kenya Program Manager; <em><u>Responsibilities</u></em>: Contribute to the study design, protocol development, manage study tools piloting, training of data collectors, data management, data analysis, interpretation of the study findings, dissemination of findings, day-to-day study management, quality assurance and adherence of the study protocol</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Ruth Wamae, MMed, MSc, MBChB</p>\n </td>\n <td>\n <p>\n Kenya Obstetrical and Gynecological Society PPH National Champion; <em><u>Responsibilities</u></em>: Contribute to the study design, tools and protocol development, offer technical leadership in the implementation of the study, day-to-day study implementation, support study findings interpretation and dissemination of findings, quality assurance and ensure compliance with study protocol including government IRB policies and procedures</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Stephen Mwatha, MSc, MBChB</p>\n </td>\n <td>\n <p>\n Makueni County Department of Health Partner Liaison; <em><u>Responsibilities</u></em>:</p>\n <p>\n Support the study design, tools and protocol development, provide study approval at the county level, offer technical leadership in the implementation of the study, contribute to the study interpretation of findings, support dissemination of the findings and day-to-day study implementation to ensure compliance with study protocol including government IRB policies and procedures</p>\n </td>\n </tr>\n <tr>\n <td>\n <p>\n Dr. Caroline Mwanthi, MSc</p>\n </td>\n <td>\n <p>\n Makueni County Department of Health County Research and Knowledge Management Coordinator; <em><u>Responsibilities</u></em>: Contribute to the study design, tools and protocol development, offer technical support in the implementation of the study, day-to-day study implementation, support study findings interpretation and dissemination of findings and ensuring compliance with study protocol and all agencies including government IRB policies and procedures.</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n N/A.</p>\n<p>\n The study is not a clinical trial study.</p>\n<p>\n Ethical Review committee in Kenya, KEMRI  and respective ERC in India, Guinea and DRC have approved the protocol.</p>\n<p>\n NACOSTI has issued the research permit for this study, Licennse No (NACOSTI/P/23/31018)</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_durationN/A
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_area36 public health facilities in Makueni County
      • single_site_physical_addressMakueni County
      • single_site_contact_personDr. Caroline Kaeni
      • single_site_telephone+254725776613
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites
      • multi_country_listKenya, Democratic Republic of Congo (DRC), Guinea and India
      • data_monitoring_committeeYes
      • total_enrolment_per_siteTool 1: 16-20 participants (KII for ANC providers involved in ADMSA for PPH prevention\nTool 2: 32-40 participants (FGD for Community Health workers in targeted areas for ADMSA)\nTool 3: 6-12 participants (KII for community leaders and organization in areas targeted for ADMSA)\nTool 4: 20-30 participants (IDI for women who received advance distribution of misoprostol for PPH prevention)\nTool 5: Maximum 282 participants (Structured survey for maternity providers)\nTool 6: 20-24 participants (KII for maternity care providers at facilities)\nTool 7: 20-24 participants (KII for health facility management)\nTool 8: 12-20 participants (KII for National and sub-national policy makers and other project stakeholders
      • total_participants_worldwide2205
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenYes
      • subjects_nursing_womenYes
      • subjects_emergency_situationYes
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameFreda Nyaga
      • investigator1_middle_nameKalema
      • investigator1_family_nameNyaga
      • investigator1_qualificationMonitoring and Evaluation Manager
      • investigator1_professional_addressJhpiego Kenya, 14 Riverside Arlington Block, 2nd Floor
      • investigator1_telephone+254721936891
      • investigator1_emailFredaKalema.Nyaga@jhpiego.org
      • organisations_transferred_No
      • number_participants452
      • notification
      • approval_date30-05-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted20-03-2024
      • is_child0
      • unsubmitted1
      • initial_date_submitted16-01-2024
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been resolved.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-05-30 11:02:40
      • created2023-12-19 14:27:05
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1026
        • application_id1360
        • given_nameDaisy Ruto
        • middle_nameJerop
        • family_nameRuto
        • qualificationMMED OBS/GYN, MBChB
        • professional_addressJhpiego Kenya, 14 Riverside Arlington Block, 2nd Floor
        • telephone0708822611
        • emaildaisy.ruto@jhpiego.org
        • created2023-12-19 16:00:08
        • modified2024-03-20 16:36:25
    • SiteDetail(array)
      • 0(array)
        • id1655
        • application_id1360
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2023-12-19 16:00:08
        • modified2024-03-20 16:36:25
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id715
        • application_id1360
        • sponsorJhpiego Corporation
        • sponsor_typeOthers
        • contact_personPaul Nyachae
        • address14 Riverside
        • telephone_number0111013400
        • fax_number
        • cell_number0722337625
        • email_addresspaul.nyachae@jhpiego.org
        • created2023-12-19 16:00:08
        • modified2024-03-20 16:36:25
  • 1(array)
    • Application(array)
      • id294
      • user_id38
      • trial_status_id7
      • abstract_of_study<p>\n Less than a year after Artemisinin-based combination therapies (ACTs) were recommended for the treatment of falciparum malaria, concerns about artemisinin resistance development along the Cambodian-Thai border were voiced. Artemisinin resistance has been poorly characterized, and is difficult to detect by classical laboratory approaches.  In-vitro tests have not consistently detected reduced pharmacodynamic responses to artemisinin drugs, and molecular markers conferring artemisinin resistance have not yet been determined.  This study aims to assess the degree of artemisinin resistance in adult and pediatric subjects presenting with uncomplicated falciparum malaria in Western Kenya. The study treatments will be Artemether Lumefantrine (AL) and Artesunate Mefloquine (ASMQ). In order to accurately evaluate the artemisinin derivative without the confounding influence of the partner drug, ASMQ will be sequentially administered. In-vivo and in-vitro methodologies, including pharmacokinetic methods, will be employed. Data generated from this study, both on its own and when compared to and pooled with data from similar studies that will be conducted in Ghana, Peru and Thailand, will potentially enable the identification of key markers that may assist in the early detection of resistance, and also to better understand the development of resistance to ACTs, and thus inform both local and international policy regarding ACT use.</p>\n
      • study_title<p>\n In vivo and in vitro efficacy of artemisinin combination therapy in Kisumu County, Western Kenya.</p>\n
      • laymans_summary(null)
      • short_titleInvivo I study
      • protocol_noECCT/14/05/02
      • version_no3.5
      • date_of_protocol10-02-2014
      • study_drugArtemether Lumefantrine and Artesunate Mefloquine
      • disease_conditionMalaria
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameArtemether Lumefantrin and Artesunate Mefloquine
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressvictorine.owira@usamru-k.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantVictorine Owira
      • declaration_date114-05-2014
      • declaration_principal_investigatorDr Ben Andagalu
      • declaration_date214-05-2014
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<ul>\n <li>\n Adult/child aged between 6 months and 65 years inclusive (minimum weight 11kg), presenting with a measured temperature of ≥37.5⁰C, or history of fever within 24 hours prior to presentation</li>\n <li>\n Mono-infection with Plasmodium falciparum (refer to section 7.6.10.2.1 below)</li>\n <li>\n Baseline parasitemia of 2000 - 200,000 asexual parasites/µl</li>\n <li>\n Ability to provide informed consent</li>\n <li>\n Willingness and ability to comply with the study protocol for the duration of the study</li>\n <li>\n Willingness to remain in the hospital for 3 days</li>\n</ul>\n
      • principal_exclusion_criteria<ul>\n <li>\n Presence of signs of severe malaria as defined in section 7.3.2.1 below</li>\n <li>\n Presence of severe anemia, defined as hemoglobin level below 6 g/dl</li>\n <li>\n Presence of mixed Plasmodium infection, or mono-infection of non-falciparum Plasmodium</li>\n <li>\n Inability to take oral medication</li>\n <li>\n History of allergy or contraindications to the study treatments</li>\n <li>\n Lactating or pregnant females</li>\n <li>\n Any condition that the investigator feels will result in an unfavorable outcome should the potential subject participate in the study</li>\n</ul>\n
      • primary_end_points<p>\n The primary study endpoint is the time to parasitaemia clearance from day 0 after treatment initiation. Parasitaemia clearance is defined as the parasitaemia disappearance at day 1, day 2 and up to day 28 after treatment.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • 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
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n The study site is well equiped to handle phase I to phase IV clinical trials. It has fully equiped clinical laboratory with functional hematology, biochemistry, microbiology and microscopy department. The site also has access to a level 2 basic science laboratory situated in the town office which is about 40 km from the research site. There is clinical pharmacy, consultation rooms, nursing station, emergency room equiped with emergency kits.</p>\n<p>\n The study has 7 investigators, 1 clinical research coordinator, 1 internal quality control personnel, 5 laboratory technologists, 1 pharmacyst, 3 pharm techs, 5 clinical officers, 7 nurses and numerous field workers</p>\n
      • other_details_explanation<p>\n The study is local investigator initiated</p>\n
      • other_details_regulatory_notapproved<p>\n Not Applicable</p>\n
      • other_details_regulatory_approved<p>\n Not Applicable</p>\n
      • other_details_regulatory_rejected<p>\n Not Applicable</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable</p>\n
      • estimated_duration42 days per partcipant
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKombewa Clinical Research Center
      • single_site_physical_addressOff Kisumu Bondo road opposite Kombewa District Hospital
      • single_site_contact_personDr Ben Andagalu
      • single_site_telephone+254716004851
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeNo
      • total_enrolment_per_site118
      • total_participants_worldwide118
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • 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_nameBen
      • investigator1_middle_name
      • investigator1_family_nameAndagalu
      • investigator1_qualificationMD,MSc
      • investigator1_professional_address54-40100 Kisumu, Kenya
      • investigator1_telephone+254716004851
      • investigator1_emailBen.Andagalu@usamru-k.org
      • organisations_transferred_No
      • number_participants118
      • notification
      • approval_date14-07-2014
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted14-05-2014
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2016-04-03 05:48:21
      • created2014-05-14 08:50:04
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id203
        • application_id294
        • given_nameBen
        • middle_name
        • family_nameAndagalu
        • qualificationMD, MSc
        • professional_address54-40100 Kisumu, Kenya
        • telephone+254716004851
        • emailBen.Andagalu@usamru-k.org
        • created2014-05-14 08:56:10
        • modified2014-05-14 18:40:59
    • SiteDetail(array)
      • 0(array)
        • id252
        • application_id294
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2014-05-14 08:56:10
        • modified2014-05-14 18:40:59
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id162
        • application_id294
        • sponsorDepartment of Emerging Infectious Diseases of the United States Army Medical Research Unit
        • sponsor_type(null)
        • contact_personCOL Roddney Coldren
        • address54-40100 Kisumu
        • telephone_number+254-20-272-9303
        • fax_number+254-20-271-4592
        • cell_number+254 (0)700 881955
        • email_addressrodney.coldren@usamru-k.org
        • created2014-05-14 08:56:10
        • modified2014-05-14 18:40:59
  • 2(array)
    • Application(array)
      • id264
      • user_id127
      • trial_status_id5
      • abstract_of_study<p>\n According to KDHS 2008/9 the under 5-mortality rate has dropped from 115 per 1000 in 2003 KDHS, to 74 per 1000 in 2008, this represents an annual decline rate of 0.9%. Unless this rate is accelerated to at least 4.5%, Kenya is unlikely to meet MDG 4 by 2015. Integrated community case management (iCCM) coupled together with the administration of vitamin A supplements (VAS), is an important and viable option of reducing the mortality of children under the age of five <em>due to pneumonia, malaria and diarrhea</em>. Implementation of the iCCM in Kenya still remains inadequate. The main challenges to implementation include: inadequate training among the CHWs including little follow up post training in iCCM.</p>\n
      • study_title<p>\n integrated community case management (iCCM) in Homabay County, Kenya</p>\n
      • laymans_summary(null)
      • short_title(null)
      • protocol_noECCT/14/02/01
      • version_noversion 1
      • date_of_protocol28-01-2014
      • study_drugAmoxicillin Dispersable tablets
      • disease_conditionpneumonia, diarrhoea and malaria
      • 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_nameAmoxicillin dispersable tablets
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressmaricianah@yahoo.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicant+254 732 390 992
      • declaration_date128-01-2014
      • declaration_principal_investigatorDr. Onono Maricianah, Principal Investigator
      • declaration_date228-01-2014
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<p>\n -Children under 5 years</p>\n<p>\n -Children suffering from Pneumonia, Diarrhoea and Malaria</p>\n<p>\n  </p>\n
      • principal_exclusion_criteria<p>\n -Adults</p>\n<p>\n -Children over 5 years</p>\n<p>\n -Emergency cases</p>\n<p>\n -Children not suffering from Pneumonia, Diarrhoea and Malaria</p>\n
      • primary_end_points<div>\n <p>\n - Proportion of under five years old children with pneumonia treated with antibiotics</p>\n <p>\n -Proportion of CHWs who are able to rationally use antibiotics for treatment of pneumonia</p>\n <p>\n -Proportion of CHWs who are able to account for essential iCCM drugs and commodities utilized every three months.</p>\n <p>\n -Proportion of mothers with sick infants who sought care from a CHW as the primary caregiver</p>\n <p>\n -Proportion of under five years old children who had a repeat visit from the CHW after initial treatment or referral</p>\n <p>\n -Proportion of CHWs who receive supervision for iCCM in the last 3 months</p>\n <p>\n -Proportion of under five children seen by the CHW and referred</p>\n <p>\n -Proportion of children aged 6 to 59 months who received VAS on a semi-annual basis.</p>\n <p>\n -Proportion of CHWs who are able to correctly administer VAS, defined as giving vitamin A supplementation to children aged 6 to 59 months on a semi-annual basis in the County</p>\n <p>\n -Proportion of children treated for pneumonia who do not respond to treatment (experience treatment failure or relapse)</p>\n</div>\n<p>\n  </p>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n Dr. Onono Maricianah, M.B.Ch.B, MSc Clinical Research - Principal Investigator</p>\n<p>\n Dr. Bukusi Elizabeth, MBChB, M.Med (ObGyn), MPH, PhD , PGD(Research Ethics) - Co-Investigator</p>\n<p>\n Akama Eliud, BSc, Diploma Community Health Nursing - Co-Investigator</p>\n<p>\n Owuor Kevin, MSc Research Methods, BSc. Statistics - Co-Investigator/Statistician</p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n -Kenya Medical Research Institute</p>\n<p>\n -World Health Organisation</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration18 months
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaHomabay County
      • single_site_physical_addressLumumba Health Center, Agoi Street, Kisumu-Kenya
      • single_site_contact_personDr. Onono Maricianah
      • single_site_telephone+254 732 390 990
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_siteN/A
      • total_participants_worldwideN/A
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifychildren under 5 years
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameElizabeth
      • investigator1_middle_nameAnne
      • investigator1_family_nameBukusi
      • investigator1_qualificationMBChB, M.Med (ObGyn), MPH, PhD .
      • investigator1_professional_addressP.O Box 19464- 00202 ,Nairobi
      • investigator1_telephone+254 720 617 503
      • investigator1_emailebukusi@kemri-ucsf.org
      • organisations_transferred_Yes
      • number_participants888
      • notification<p>\n N/A</p>\n
      • approval_date21-05-2013
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted06-02-2014
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2018-10-15 14:01:51
      • created2014-01-23 17:18:34
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id191
        • application_id264
        • given_nameMaricianah
        • middle_nameAtieno
        • family_nameOnono
        • qualificationMB.Ch.B MSc clinical research
        • professional_addressP.O Box 614 Postal Code 40100, Kisumu-Kenya
        • telephone+254 732 390 992
        • emailmaricianah@yahoo.com
        • created2014-01-28 16:02:03
        • modified2014-02-06 16:42:50
    • SiteDetail(array)
      • 0(array)
        • id238
        • application_id264
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
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        • misc(null)
        • created2014-01-28 16:02:03
        • modified2014-02-06 16:42:50
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id150
        • application_id264
        • sponsorUNICEF & WHO
        • sponsor_type(null)
        • contact_personKetema Aschenaki Bizuneh
        • addressP.O. Box 44145-00100, UNICEF, Kenya Country Office
        • telephone_number254 (20) 762 2209
        • fax_number254 (20) 762 27 46
        • cell_number+254 719 390 115
        • email_addresskbizuneh@unicef.org
        • created2014-01-28 16:02:03
        • modified2014-02-06 16:42:50
  • 3(array)
    • Application(array)
      • id633
      • user_id799
      • trial_status_id5
      • abstract_of_study<p>\n Antimicrobial resistance (AMR) has become a major issue in global health. Despite progress in the reduction of under 5 mortality rates in recent decades, the proportion of neonatal deaths occurring within this age group has increased, with almost one quarter of all neonatal deaths occurring due to serious bacterial infection. Common bacteria causing neonatal sepsis are now exhibiting widespread resistance to several classes of antibiotics. There is an urgent need to discover new, effective treatments and re-evaluate existing therapeutic agents to treat infections potentially caused by multi-drug resistant (MDR) pathogens. Gram-negative bacteria (GNB) predominate as the cause of neonatal sepsis, and are increasingly associated with high rates of resistance to the currently recommended WHO empirical therapy regimen of ampicillin/penicillin and gentamicin. There is therefore a need to develop an updated empiric regimen with improved efficacy in the context of increasing MDR sepsis in neonates. New antimicrobials under development will be expensive once licensed, and there are currently virtually no planned trials to assess their efficacy in neonates in low- and middle-income countries (LMICs).</p>\n<p>\n One potential strategy is utilising an existing off-patent (and therefore affordable) antibiotic available in intravenous and oral formulations – fosfomycin. Fosfomycin has a wide spectrum of activity against Gram-positive and Gram-negative bacteria causing neonatal sepsis. It is mainly used for resistant urinary tract infections in adults, but has licenced neonatal and paediatric doses in Europe (though dosing regimens vary between countries). Both oral and IV formulations are available. A large clinical trial to assess the efficacy of a fosfomycin plus an aminoglycoside combination (compared to the current WHO recommended ampicillin and gentamicin) is anticipated, including sites in Kenya. The ultimate aim is for fosfomycin to be included in the WHO Essential Medicines List for children (EMLc) and be available for use in developing countries, where rates of resistance to ampicillin and gentamicin have been estimated at over 40%. The first steps before this trial are to clarify the pharmacokinetics (PK) and safety profile of fosfomycin in neonates, as well as generating further information regarding local patterns of bacterial susceptibility to fosfomycin. The aim of this study is to fulfil both these steps. Fosfomycin (IV and oral) PK will be investigated among 60 babies admitted to hospital and being treated for presumed sepsis; administered alongside the standard antibiotics. Another 60 babies receiving standard treatment only (without PK sampling) will be monitored in the same way to compare adverse events. In the laboratory at CGMR-C, previoiusly archived bacterial isolates will be tested for their sensitivity to fosfomycin.</p>\n
      • study_title<p>\n Intravenous and Oral Fosfomycin in Hospitalised Neonates with Clinical Sepsis: an open-label safety and pharmacokinetics study</p>\n
      • laymans_summary<p>\n Among babies presenting with signs of serious infection, or who develop these signs whilst in hospital, bacterial resistance to the antibiotics that are normally used is increasing. This means that babies with infections may be at a higher risk of dying. In Africa, alternative antibiotics are often expensive and may themselves cause the bacteria to become resistant. Therefore, new treatment strategies are needed. Fosfomycin is a potentially inexpensive antibiotic that is licenced for use in children in Europe and may be useful to resource-poor countries. It has a good safety profile in children and is expected to be effective against infections that do not respond to the currently used antibiotics. However, more information is needed to inform how fosfomycin should be used in babies in Kenya.</p>\n<p>\n We wanted to find out what doses of fosfomycin would be most suitable for sick newborns in Kenya in order to optimise its use in an effective and safe way. We also wanted to find out how well local bacteria that have been previously found (and stored) from patients at Kilifi County Hospital are able to be killed by fosfomycin.</p>\n<p>\n The study took place in Kilifi County Hospital, Kilifi, Kenya.</p>\n<p>\n The study measuring the levels of antibiotics in newborn babies, included 120 babies admitted to the hospital with presumed infection. Sixty-one (61) of these babies were given fosfomycin in addition to standard treatment and drug levels measured; the other 59 received standard treatment only.</p>\n<p>\n We asked parents and guardians of all babies aged 28 days or less who were admitted to Kilifi County Hospital with signs of infection to participate, unless they were being transferred from another hospital, already received other antibiotics by injection, were very sick or premature, or had abnormally high salt (sodium) levels in their blood.</p>\n<p>\n After providing information and answering any questions, informed consent was requested from the child’s parent or guardian. A doctor or study clinical officer examined the baby and took the usual admission investigations, then prescribed the two antibiotics that are currently recommended by the WHO for the treatment of presumed infection in babies (ampicillin and gentamicin).</p>\n<p>\n Half of the babies were selected randomly to receive intravenous fosfomycin as well as the standard antibiotics. The nurse or clinical officer then took two blood samples to check fosfomycin levels. After a minimum of four doses of intravenous (IV) fosfomycin (over 48 hours), when their condition improved and they were tolerating feeds by mouth, the baby was then changed on to oral fosfomycin. A further two blood samples were collected after the first oral dose of fosfomycin, including one to check the kidney and liver function and level of salts in the blood (which is currently a routine investigation). Each of these blood samples was approximately 0.5ml, giving a total for this research of  approximately 2.5ml (half a teaspoon) for checking the drug levels, and a further 1ml (a quarter of a teaspoon) for checking the level of salts in their blood.</p>\n<p>\n For all babies, a blood test was taken (which is normally part of routine care) at around 48 hours to check the blood count, kidney and liver function and level of salts in the blood. If a baby had a lumbar puncture as part of their normal treatment (if their doctor was concerned about an infection in their brain), the fosfomycin level in the fluid surrounding their brain was also checked.</p>\n<p>\n The babies were closely followed by the study team, working together with the hospital staff to provide the best care available in the hospital. On day 7, any babies who remained as inpatients had a blood test to check blood count, kidney and liver function and level of salts in the blood (and 0.5ml drawn for fosfomycin levels in the group receiving this antibiotic). Breastfeeding and health counselling was given according to national guidelines. All babies were followed up in the outpatients’ clinic 28 days after their presentation to hospital and parents/guardians could also phone the study team directly on a study-specific mobile phone, or bring the baby to the ward prior to that review, in case of health concerns.</p>\n<p>\n Additional staff (clinical officers and nurses) were recruited to undertake study duties and assist in general care on the ward, adding to the staff available. Training was enhanced for all paediatric ward staff on the treatment of babies presenting with infections, and on the prevention of infections within the hospitals. We also made available additional antibiotics as needed, if a baby continued to have signs of infection despite treatment or remained unwell. Drawing a blood sample carried the potential risks of bruising to the vein or infection, and careful training on procedures was done to help prevent these. There was a small risk of the baby having high levels of salt (sodium) in their blood due to the salt content of the fosfomycin injection. Improved monitoring of kidney function and blood salt levels was done to offset these risks.</p>\n<p>\n This study done is leading up to a large clinical trial assessing how effective fosfomycin is to treat babies with infections, and if it is effective, will support efforts to make fosfomycin available at low cost for Kenya and other countries.  This will help babies to be more effectively treated when bacteria are resistant to the currently used antibiotics.</p>\n<p>\n  </p>\n
      • short_titleNeo-Fosfo
      • protocol_noECCT/17/10/01
      • version_noV1.1
      • date_of_protocol23-08-2017
      • study_drugFosfomycin (Fosfocina and Fomicyt)
      • disease_conditionNeonatal Sepsis
      • 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_nameFosfomycin
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressecorreia@dndi.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr Monique Wasunna
      • declaration_date103-10-2017
      • declaration_principal_investigatorProf James Berkely
      • declaration_date203-10-2017
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<p>\n Criteria for inclusion of subjects (for pharmacokinetics):</p>\n<p>\n Neonates defined as:</p>\n<p>\n • Age 0 to 28 days inclusive</p>\n<p>\n • Weight >1500g</p>\n<p>\n • Born (an estimated) >34 weeks gestation (calculated as per the Ballard Maturational Assessment)</p>\n<p>\n • Admitted to hospital and eligible to receive IV antibiotics, according to national guidelines</p>\n<p>\n All neonates presenting to Kilifi County Hospital meeting the above criteria will be screened for inclusion in a systematic recruitment process</p>\n
      • principal_exclusion_criteria<p>\n Criteria for exclusion of subjects:</p>\n<p>\n • Baseline sodium level > 150mmol/L</p>\n<p>\n • Baseline creatinine >150 micromol/L</p>\n<p>\n • Presenting with severe (grade 3) Hypoxic Ischaemic Encephalopathy (HIE), defined as per Sarnat and Sarnat44 as a stuporous, flaccid infant (with or without seizure activity) with suppressed brainstem and autonomic functions and absent reflexes</p>\n<p>\n • Requiring cardiopulmonary resuscitation on admission</p>\n<p>\n • Jaundice requiring exchange transfusion</p>\n<p>\n • Admitted as a transfer after an overnight inpatient stay at another hospital</p>\n<p>\n • Known allergy or contraindication to fosfomycin</p>\n<p>\n • A specific clinical indicatio</p>\n
      • primary_end_points<p>\n Estimation of the pharmacokinetic disposition and absorption parameters of IV and oral fosfomycin in neonates with clinical sepsis with sufficient precision such that a dose schedule can be recommended for a future efficacy trial.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyPharmacokinetic and Pharmacodynamic (safety)
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n KEMRI-Kilifi WTRP is a multi disciplinary research facility with over 600 employees engaged in the facility at Kilify, including clinical officers, nursing staff, research officers, laboratory scientists and field workers.</p>\n<p>\n The clinical facilities include a functional High Dependency Unit. For neonates (our study population), this includes the provision  of emergency medical facilities, incubator care, oxygen and saturation monitoring, phototherapy for jaundice, parenteral medication administration and feeding support. The site is staffed by 2 medical officers at all times and 8 nursing staff including a clinical nurse specialist (also a study investigator).</p>\n<p>\n The study will be coordinated by a number of local investigators:</p>\n<p>\n Professor Jay Berkley, Professor of Paediatric Infectious Disease, FRCPCH FMedSci</p>\n<p>\n Dr Christina Obiero: Clinical Research Officer (MBChB), Clinical Research Fellow</p>\n<p>\n Dr Phoebe Williams: MBBS (Hons), MSc, Dip. Paeds</p>\n<p>\n Dr Neema Mturi: Paediatrician (MBChB)</p>\n<p>\n Dr Claire Gordon: Clinical Microbiologist MBBS PhD</p>\n<p>\n Dr Martin Ongas: Research Fellow, BSc Analytical Sciences</p>\n<p>\n Mr Johnstone Thitiri: Clinical Trials Coordinator, BSc, MSc</p>\n<p>\n Ms Sheila Murunga: Clinical Trial Data Manager, BSc Apllied Statistics</p>\n<p>\n Ms Mwananvua Boga: Clinical Nurse, Consultant in Intensive Care Medicine, RN, MSc</p>\n<p>\n Mr Joseph Waichungo: Microbiology Research Scientist, BSc, MSc</p>\n
      • other_details_explanation<p>\n Neonatal sepsis has a high risk of morbidity and mortality. The current WHO and national guidelines recommend antibiotics to which resistance is reported in neonatal populations, although the available data is limited. Research on alternative empirical regimens for neonatal sepsis which are affordable, safe and cost-effective, with a step-down oral option, is needed. AMR is an issue of global public health concern and is one of the WHO’s global health prority areas. Understanding the benefits, risks, MIC capacity and PK of fosfomycin will influence global policy on the case management of neonates with sepsis in Kenya and international settings.</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_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_comparatorampicillin and gentamycin
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherYes
      • design_controlled_medicinal_specifyAmpicillin, Gentamicin
      • single_site_member_stateYes
      • location_of_areaKEMRI-WTRP
      • single_site_physical_addressKEMRI CGMR-Coast, PO Box 230-80108, Kilifi, Kenya
      • single_site_contact_personDr Phoebe Williams
      • single_site_telephone+254 740 310 773
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_siteNA single site
      • total_participants_worldwideNA single site
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornYes
      • population_newbornYes
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyNeonates
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJames
      • investigator1_middle_nameA
      • investigator1_family_nameBerkley
      • investigator1_qualificationFRCPCH FMedSci
      • investigator1_professional_addressKEMRI CGMR-Coast PO Box 230-80108, Kilifi, Kenya
      • investigator1_telephone+254 720 867 011
      • investigator1_emailjberkley@kemri-wellcome.org
      • organisations_transferred_Yes
      • number_participants120
      • notification
      • approval_date18-12-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted05-10-2017
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<div>\n Objectives:</div>\n<div>\n The primary objective was to improve the understanding of the pharmacokinetics (PK) and safety of fosfomycin amongst newborns aged ≤28 days hospitalised with clinically diagnosed sepsis and provide detailed information regarding the antimicrobial susceptibility of local invasive bacteria to fosfomycin:</div>\n<div>\n • To estimate the PK disposition parameters of intravenous (IV) and oral (PO) fosfomycin in neonates.</div>\n<div>\n • To assess the safety of fosfomycin, particularly with regard to possible elevation of sodium after 48 hours of IV fosfomycin administration in neonates.</div>\n<div>\n • To estimate the PO bioavailability (F) of fosfomycin in neonates.</div>\n<div>\n • To generate preliminary data on the safety of PO fosfomycin in neonates.</div>\n<div>\n • To generate a recommended dosing schedule for future IV and PO fosfomycin efficacy trials.</div>\n<div>\n • To collect information regarding the tolerability of PO fosfomycin.</div>\n<div>\n The secondary objective was to gain information regarding susceptibility patterns of local bacterial species to fosfomycin.</div>\n<div>\n <div>\n  </div>\n <div>\n Methodology:</div>\n <div>\n A randomised controlled trial evaluating the safety and PK of IV and PO fosfomycin (in particular sodium levels and adverse events [AEs]) compared to the standard of care (SOC) antibiotics (ampicillin/gentamicin) among neonates admitted to a rural hospital in Kenya and eligible for IV antibiotics under current Kenya national guidelines.</div>\n <div>\n  </div>\n <div>\n <div>\n Number of Subjects (planned and analysed):</div>\n <div>\n Planned: 120, Analysed: 120</div>\n <div>\n  </div>\n <div>\n <div>\n Diagnosis and Main Criteria for Inclusion: Parents and guardians of all babies aged 28 days or less who were admitted to Kilifi County Hospital with signs of infection were asked to consent for their child to participate, unless they were being transferred from another hospital, already received other antibiotics by injection, were very sick or premature, or had abnormally high salt (sodium) levels in their blood.</div>\n <div>\n Criteria for inclusion of subjects (for pharmacokinetics):</div>\n <div>\n Neonates were defined as:</div>\n <div>\n • Age 0 to 28 days inclusive.</div>\n <div>\n • Weight >1500 g.</div>\n <div>\n • Born (an estimated) >34 weeks gestation (calculated as per the Ballard Maturational</div>\n <div>\n Assessment).</div>\n <div>\n • Admitted to hospital and eligible to receive IV antibiotics, according to national guidelines.</div>\n </div>\n <div>\n  </div>\n <div>\n <div>\n Test Product:</div>\n <div>\n Fosfomycin or SOC (ampicillin + gentamicin)</div>\n <div>\n  </div>\n <div>\n <div>\n Dose and Mode of Administration:</div>\n <div>\n 120 subjects were randomised 1:1 to SOC antibiotics plus up to 7 -days of fosfomycin (n=61); or SOC (n=59) antibiotics only (ampicillin 50 mg/kg twice daily and gentamicin 3 mg/kg for babies <2 kg or 5 mg/kg for babies >2 kg once daily for 7 days, as per Kenyan guidelines).</div>\n </div>\n <div>\n  </div>\n <div>\n <div>\n Duration of Treatment:</div>\n <div>\n IV fosfomycin was given for at least 48 hours together with SOC (ampicillin + gentamicin) then changed to PO fosfomycin, once the baby was able to tolerate oral medication to complete a total of 7 days of fosfomycin (or until the baby was discharged).</div>\n <div>\n  </div>\n <div>\n <div>\n Criteria for Evaluation:</div>\n <div>\n Efficacy:</div>\n <div>\n Not applicable. All neonates enrolled received SOC antibiotics, so there were no efficacy concerns /analysis. Children were monitored closely for toxicity and the study drug stopped in individual cases if warranted medically.</div>\n <div>\n Safety:</div>\n <div>\n Safety was assessed based on the following variables:</div>\n <div>\n • AEs and serious adverse events (SAEs).</div>\n <div>\n • Haematology and serum chemistry including sodium.</div>\n <div>\n • Physical examination.</div>\n <div>\n • Vital signs.</div>\n <div>\n  </div>\n <div>\n <div>\n Statistical Methods:</div>\n <div>\n • PK modelling and dosing simulations were undertaken by non-linear mixed-effects modelling using NONMEM® software.</div>\n <div>\n • Shift tables were used to present changes in biological parameters between baseline and Day 2 and baseline and Day 7 (if available).</div>\n <div>\n • Software analysis was done using STATA version 15.1.</div>\n <div>\n  </div>\n <div>\n <div>\n Pharmacokinetic Results:</div>\n <div>\n A 3 compartment population PK model was developed using the IV, PO and cerebrospinal fluid (CSF) PK data. Weight, post menstrual age (PMA), postnatal age on clearance, and CSF protein on CSF uptake were identified as covariates during model development.</div>\n <div>\n  </div>\n <div>\n Safety Results:</div>\n <div>\n Overall, the AEs recorded during the study were all considered unrelated to fosfomycin or SOC. AEs (any grade) were less frequent in the SOC + fosfo group. There were 7 unrelated deaths (4 in the SOC + fosfo group) due to disease progression or underlying conditions. Two subjects (1 in the SOC and 1 in the SOC + fosfo group) experienced 3 SAEs (neonatal meningitis, patent foramen ovale and worsening of sepsis) that resulted in study discontinuation.</div>\n <div>\n No significant abnormalities were recorded from clinical laboratory parameters or vital signs throughout the study for both treatment groups. There was no clinically significant difference between the 2 treatment groups with regard to plasma sodium or potassium levels, liver function or renal function at 3 time points (baseline, Day 2 or Day7).</div>\n <div>\n  </div>\n <div>\n Conclusions:</div>\n <div>\n The 3-compartment population PK model adequately described the observed plasma and CSF exposure, which enables estimation of all model parameters with reasonable levels of precision. Weight, PMA, postnatal age on clearance, and CSF protein on CSF uptake were identified as covariates during model development.</div>\n <div>\n Based on safety results, IV and PO fosfomycin at study dose levels could be considered as well tolerated in neonates.</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
      • implication_results<p>\n This clinical trial provides a significant step towards improving treatment regimens for neonatal sepsis. Adding IV and oral fosfomycin to the currently recommended WHO first line antibiotics was not associated with an increased frequency of adverse events. Specifically, IV fosfomycin did not affect plasma sodium at the dose evaluated (100mg/kg twice daily). A small reduction in plasma potassium at day 2 is unlikely to be of clinical significance. This dose is consistent with the range of doses recommended by the EMA. Oral fosfomycin was well-tolerated without evidence of osmotic diarrhoea compared to standard of care.</p>\n<p>\n Our main pharmacokinetic finding was that in, in common with other antimicrobial agents, postnatal age was a key covariate in describing changes in the clearance of fosfomycin, this effect was distinct from gestational age and weight effects. For neonates aged >7 days it is likely that higher IV doses than 100mg/kg used in our study are required to promote bactericidal activity, whereas bacteriostasis could be achieved (<strong>Figure 3</strong>). Resistance suppression could only be achieved with the most sensitive of organisms (MIC <0.5mg/L).</p>\n<p>\n Both these findings point to a need to use fosfomycin in combination with another antimicrobial. Whilst our data do not suggest safety concerns at this higher dose, monitoring electrolytes where this is possible may be helpful in confirming this. This higher dose is also consistent with the recently revised EMA dosing recommendations for fosfomycin for infants and neonates. The presence of fosfomycin-inactivating enzymes in transferrable plasmids also necessitates the use of fosfomycin as a combination to reduce the spread of Fosfomycin resistance. Our estimates are based on limited <em>in vitro </em>pharmacodynamic data and initial studies evaluating fosfomycin in combination with other antibiotics including beta lactams and aminoglycosides using hollow fibre infection model have demonstrated that antimicrobial combinations could delay the emergence of resistance.45,46 Further clinical trials to evaluate the use of such combinations in neonatal sepsis in the LMIC setting incorporating fosfomycin are also under development.</p>\n<p>\n To our knowledge this is the first study to enable model-based estimation of fosfomycin oral bioavailability using a crossover design in neonates, a key factor in properly managing any oral step-down therapy. This study showed that even at higher per kg doses fosfomycin absorption occurs to a greater extent and at a faster rate in neonates than in healthy adult receiving the equivalent (calcium) salt form.49 While only a small amount of CSF data was collected, it has provided good evidence that fosfomycin can cross the meninges in neonates, achieving appreciable concentrations in the CSF. The intention however is to collect further data before making conclusions regarding fosfomycin dosing for meningitis.</p>\n<p>\n In light of fosfomycin’s favourable susceptibility profile against community and hospital acquired organisms,this trial provides the basis on which to evaluate the efficacy and cost-effectiveness of fosfomycin within combination therapy in multiple clinical settings compared to current standard of care either as part of an empiric regimen in hospitalized neonates at high risk of sepsis due to multidrug resistant bacteria or as part of a combination regimen to treat microbiologically-confirmed carbapenem resistant infections.</p>\n<p>\n Our trial has limitations; single-centre recruitment and exclusion of the most unwell neonates at enrolment was judged important given the very limited prior information in neonates but may limit generalisability. Strengths of this trial include a low loss to follow-up rate, standardised observation and the high proportion of PK samples collected with robust timing and dosing information – a logistically challenging exercise in any setting.</p>\n<p>\n Increasing AMR in a population who may die rapidly as a result of inadequate antimicrobial coverage is of concern given the shortage of new antibiotics in the pipeline. Fosfomycin offers potential as part of an affordable regimen with ease of administration (over a short infusion) and a simple twice daily dosing schedule.</p>\n<p>\n  </p>\n
      • quantity_imported828 bottles
      • quantity_dispensed422 bottles
      • quantity_destroyed828 bottles- 422 bottles used and 406 bottles unused
      • quantity_exported0
      • balance_site0
      • final_date0000-00-00
      • modified2023-09-21 12:29:31
      • created2017-09-18 12:41:37
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id406
        • application_id633
        • given_nameJames
        • middle_nameA
        • family_nameBerkley
        • qualificationFRCPCH FMedSci
        • professional_addressKEMRI CGMR-Coast PO Box 230-80108, Kilifi, Kenya
        • telephone+254 720 867 011
        • emailjberkley@kemri-wellcome.org
        • created2017-09-19 15:03:51
        • modified2017-10-05 15:42:44
    • SiteDetail(array)
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        • id516
        • application_id633
        • county_id(null)
        • site_name
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        • contact_details
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        • misc(null)
        • created2017-09-19 15:03:51
        • modified2017-10-05 15:42:44
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id324
        • application_id633
        • sponsorDrugs for Neglected Diseases initiative (DNDi)
        • sponsor_type(null)
        • contact_personDr Monique Wasunna
        • addressTetezi Towers, 3rd Floor, George Padmore Rd, Kilimani, PO BOX 21936-00505, Nairobi, Kenya
        • telephone_number+254 20 3995000
        • fax_number
        • cell_number+254 20 3995022
        • email_addressmwasunna@dndi.org
        • created2017-09-19 15:03:51
        • modified2017-10-05 15:42:44
  • 4(array)
    • Application(array)
      • id552
      • user_id345
      • trial_status_id1
      • abstract_of_study<p>\n <span style=\"font-size:14px;\"><strong><u>INVICTUS TRIALS: INVESTIGATION OF RHEUMATIC AF TREATMENT USING VITAMIN K ANTAGONISTS, RIVAROXABAN OR ASPRIN STUDIES</u></strong></span><br />\n  </p>\n<p style=\"text-align: justify;\">\n <span style=\"font-size:14px;\"><u>BACKGROUND:</u><br />\n In developing countries, AF, a common cardiac arrhythmia is related to rheumatic valvular heart disease (RVHD) especially mitral valve disease. With AF, the risk of stroke increases by a facroe of 5 and is reponsible for up to 20% of the stroke events. Vitamin K antagonists(VKA) have been established as effective for prevention of stroke in AF. Apsrin has been found to be less effective than VKA. However VKAs are limited by multiple drug interactions and inter-patient variabilities necessitating the need for frequent monitoring of the coagulation status to optimize efficacy and safety. This poses a challenge in developing nations. Rivaroxaban has been documented as effective in prevention of stroke in AF without the need for frequent monitoring of the coagulation status. INVICTUS trials are designed to address the need to establish the safety and efficacy of rivaroxaban for prevention of stoke in rheumatic AF.</span><br />\n <br />\n  </p>\n<div>\n <span style=\"font-size:14px;\"><u><strong>Primary Hypotheses</strong></u></span></div>\n<div>\n <span style=\"font-size:14px;\">1. In patients with rheumatic valvular heart disease (RVHD) and who are in atrial fibrillation or flutter (AF/flutter) and have other stroke risk factors, rivaroxaban is non-inferior to vitamin K antagonists (VKAs) for prevention of stroke or systemic embolism.</span></div>\n<div>\n <span style=\"font-size:14px;\">2. In patients with RVHD, either with AF/flutter but unsuitable for VKA therapy, or with sinus rhythm but with high risk, rivaroxaban is superior to aspirin for prevention of stroke or systemic embolism. Study Design</span></div>\n<div>\n <span style=\"font-size:14px;\">This program is a comprehensive evaluation of RVHD, AF/flutter and stroke. It includes three major components:</span></div>\n<div>\n <span style=\"font-size:14px;\">1. A multi-centre registry of RVHD</span></div>\n<div>\n <span style=\"font-size:14px;\">2. A prospective, randomized, parallel group, open-label clinical trial of rivaroxaban versus standard VKA therapy to evaluate non-inferiority of rivaroxaban to VKA, with testing for superiority if non-inferiority is satisfied.</span></div>\n<div>\n <span style=\"font-size:14px;\">3. A prospective, randomized, open-label superiority trial comparing rivaroxaban to aspirin in high risk patients either with AF and unsuitable for VKA or without AF and with high risk factors.</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:14px;\"><u><strong>Study Size</strong></u></span></div>\n<div>\n <span style=\"font-size:14px;\">RVHD Registry: 17,000 patients with RVHD (in addition to the existing registry which has already 3300 patients)</span></div>\n<div>\n <span style=\"font-size:14px;\">Non-Inferiority Trial of rivaroxaban versus VKAs: 4,500 patients</span></div>\n<div>\n <span style=\"font-size:14px;\">Superiority Trial of rivaroxaban versus aspirin: 2,000 patients</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:14px;\"><strong><u>Inclusion Criteria</u></strong></span></div>\n<div>\n <span style=\"font-size:14px;\">Registry: Any patient with RVHD diagnosed by echocardiography</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:14px;\"><strong>Non-Inferiority Trial:</strong></span></div>\n<div>\n <span style=\"font-size:14px;\">1. RVHD diagnosed by echocardiography at any time prior to enrollment</span></div>\n<div>\n <span style=\"font-size:14px;\">2. Age ≥18</span></div>\n<div>\n <span style=\"font-size:14px;\">3. Increased risk of stroke by any of the following</span></div>\n<div>\n <span style=\"font-size:14px;\">a) CHA2DS2-VASc score ≥ 2 OR</span></div>\n<div>\n <span style=\"font-size:14px;\">b) Moderate/Severe mitral stenosis with valve area ≤2.0 cm2 OR</span></div>\n<div>\n <span style=\"font-size:14px;\">c) Left atrial spontaneous echo contrast OR</span></div>\n<div>\n <span style=\"font-size:14px;\">d) Left atrial thrombus</span></div>\n<div>\n <span style=\"font-size:14px;\">4. Heart Rhythm</span></div>\n<div>\n <span style=\"font-size:14px;\">a) AF or Flutter should be documented on baseline 12-lead ECG, or on a previous 12-lead ECG, Holter monitor, in-hospital ECG rhythm strip or Pacemaker or ICD electrogram.</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:14px;\"><strong>Superiority Trial</strong></span></div>\n<div>\n <span style=\"font-size:14px;\">1. RVHD diagnosed by echocardiography at any time prior to enrollment</span></div>\n<div>\n <span style=\"font-size:14px;\">2. Age ≥18</span></div>\n<div>\n <span style=\"font-size:14px;\">3. Increased risk of stroke by any of the following</span></div>\n<div>\n <span style=\"font-size:14px;\">a) CHA2DS2-VASc score ≥ 2 OR</span></div>\n<div>\n <span style=\"font-size:14px;\">b) Moderate/Severe mitral stenosis with valve area ≤2.0 cm2 OR</span></div>\n<div>\n <span style=\"font-size:14px;\">c) Left atrial spontaneous echo contrast OR</span></div>\n<div>\n <span style=\"font-size:14px;\">d) Left atrial thrombus</span></div>\n<div>\n <span style=\"font-size:14px;\">4. Heart Rhythm</span></div>\n<div>\n <span style=\"font-size:14px;\">a) AF or Flutter and unsuitable for VKA therapy. (AF or Flutter should be documented on baseline 12-lead ECG, or on a previous 12-lead ECG, Holter monitor, in-hospital ECG rhythm strip or Pacemaker or ICD electrogram) OR</span></div>\n<div>\n <span style=\"font-size:14px;\">b) In the absence of AF or Flutter, patients would be eligible in the presence of any one of the following:</span></div>\n<div>\n <span style=\"font-size:14px;\">a. Left atrial enlargement ≥5.5 cm OR</span></div>\n<div>\n <span style=\"font-size:14px;\">b. Left atrial spontaneous echo contrast OR</span></div>\n<div>\n <span style=\"font-size:14px;\">c. Left atrial thrombus OR</span></div>\n<div>\n <span style=\"font-size:14px;\">d. Frequent ectopic atrial activity (>1000/24 hours) on Holter monitoring Exclusion Criteria</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:14px;\"><u><strong>Exclusion Criteria for both non-inferiority and superiority trials:</strong></u></span></div>\n<div>\n <span style=\"font-size:14px;\">1. Refusal to consent</span></div>\n<div>\n <span style=\"font-size:14px;\">2. Actively involved in any study that would compromise the protocol of INVICTUS Trial</span></div>\n<div>\n <span style=\"font-size:14px;\">3. Severe co-morbid condition with life expectancy < 1 year</span></div>\n<div>\n <div>\n <span style=\"font-size:14px;\">4. Other serious condition(s) or logistic factors likely to interfere with study participation or with the ability to complete the trial, as appropriate to country or region.</span></div>\n <div>\n <span style=\"font-size:14px;\">5. Likely to have valve replacement surgery within 6 months</span></div>\n <div>\n <span style=\"font-size:14px;\">6. Mechanical valve prosthesis or other condition requiring treatment with VKAs. Patients with deep vein thrombosis or recent pulmonary embolism can be enrolled where both VKAs and rivaroxaban are approved.</span></div>\n <div>\n <span style=\"font-size:14px;\">7. Contraindication to the study medication of the trial</span></div>\n <div>\n <span style=\"font-size:14px;\">a. Allergy to rivaroxaban</span></div>\n <div>\n <span style=\"font-size:14px;\">b. Allergy to VKAs ( non-inferiority trial)</span></div>\n <div>\n <span style=\"font-size:14px;\">c. Allergy to aspirin ( superiority trial)</span></div>\n <div>\n <span style=\"font-size:14px;\">8. Severe renal insufficiency with an calculated creatinine clearance (Cockcroft-Gault) < 15 ml/min</span></div>\n <div>\n <span style=\"font-size:14px;\">9. Serious bleeding in the past six months or at high risk for bleeding</span></div>\n <div>\n <span style=\"font-size:14px;\">10. Moderate to severe hepatic impairment</span></div>\n <div>\n <span style=\"font-size:14px;\">11. Ongoing need for dual antiplatelet therapy (patients with on-going aspirin therapy ≤100 mg per day are not excluded).</span></div>\n <div>\n <span style=\"font-size:14px;\">12. Ongoing need for dual strong inhibitors of CYP-3a4 or p-glycoprotein inhibitor.</span></div>\n <div>\n <span style=\"font-size:14px;\">13. Received an investigational drug in the past 30 days</span></div>\n <div>\n <span style=\"font-size:14px;\">14. Patients considered unsuitable for trial inclusion because of unwillingness to attend follow up visits</span></div>\n <div>\n <span style=\"font-size:14px;\">15. Women who are pregnant and/or breastfeeding</span></div>\n <div>\n <span style=\"font-size:14px;\">16. Women of child bearing age who do not use an effective form of birth control.</span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size:14px;\"><strong><u>Treatment Regimen</u></strong></span></div>\n <div>\n <span style=\"font-size:14px;\"><strong>Non-Inferiority Trial:</strong></span></div>\n <div>\n <span style=\"font-size:14px;\">Patients will be randomized either to receive rivaroxaban or any approved VKA. Treatment will be open-label.</span></div>\n <div>\n <span style=\"font-size:14px;\">1. Rivaroxaban Arm</span></div>\n <div>\n <span style=\"font-size:14px;\">- Rivaroxaban 20 mg once daily</span></div>\n <div>\n <span style=\"font-size:14px;\">- Rivaroxaban 15 mg once daily (for patients with an creatinine clearance ≥15 and <50 ml/min)</span></div>\n <div>\n <span style=\"font-size:14px;\">2. VKA Arm</span></div>\n <div>\n <span style=\"font-size:14px;\">- Any VKA approved for use in the participating country</span></div>\n <div>\n <span style=\"font-size:14px;\">- VKA titrated to achieve an INR of 2.0-3.0</span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size:14px;\"><strong>Superiority Trial:</strong></span></div>\n <div>\n <span style=\"font-size:14px;\">Patients will be randomized to receive rivaroxaban or aspirin. Treatment will be open-label.</span></div>\n <div>\n <span style=\"font-size:14px;\">1. Rivaroxaban Arm</span></div>\n <div>\n <span style=\"font-size:14px;\">- Rivaroxaban 15 mg once daily</span></div>\n <div>\n <span style=\"font-size:14px;\">- No dose reduction with renal impairment</span></div>\n <div>\n <span style=\"font-size:14px;\">2. Aspirin Arm</span></div>\n <div>\n <span style=\"font-size:14px;\">- Aspirin 75 to 100 mg once daily</span><br />\n <br />\n <div>\n <span style=\"font-size:14px;\"><strong>Registry Outcomes</strong></span></div>\n <div>\n <span style=\"font-size:14px;\">- All stroke by sub-type</span></div>\n <div>\n <span style=\"font-size:14px;\">- Systemic embolism</span></div>\n <div>\n <span style=\"font-size:14px;\">- Myocardial infarction</span></div>\n <div>\n <span style=\"font-size:14px;\">- Death by cause</span></div>\n <div>\n <span style=\"font-size:14px;\">- Recurrent rheumatic fever</span></div>\n <div>\n <span style=\"font-size:14px;\">- Prosthetic valve thrombosis</span></div>\n <div>\n <span style=\"font-size:14px;\">- Infective endocarditis</span></div>\n <div>\n <span style=\"font-size:14px;\">- Hospitalization for any cause.</span></div>\n <div>\n <span style=\"font-size:14px;\">- Valvuloplasty / Surgery</span></div>\n <div>\n <span style=\"font-size:14px;\">- Infections – Pneumonia, HIV etc. Clinical trial Efficacy Outcomes</span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size:14px;\"><strong>Primary Outcome:</strong></span></div>\n <div>\n <span style=\"font-size:14px;\">- Stroke(ischemic, hemorrhagic or undetermined type)</span></div>\n <div>\n <span style=\"font-size:14px;\">- Systemic embolism</span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size:14px;\"><strong>Secondary Outcomes</strong>:</span></div>\n <div>\n <span style=\"font-size:14px;\">- Myocardial infarction</span></div>\n <div>\n <span style=\"font-size:14px;\">- Hospitalization</span></div>\n <div>\n <span style=\"font-size:14px;\">- Vascular death</span></div>\n <div>\n <span style=\"font-size:14px;\">- Total Death</span></div>\n <div>\n <span style=\"font-size:14px;\">- Composite of stroke, myocardial infarction, systemic embolism, vascular death</span></div>\n <div>\n  </div>\n <div>\n <div>\n <span style=\"font-size:14px;\"><u><strong>Statistical Considerations</strong></u></span></div>\n <div>\n <span style=\"font-size:14px;\"><em><strong>Registry</strong></em>: A sample size of 20,000 (combined REMEDY (3000) and INVICTUS (17,000)) will ensure precise measurement of event rates as infrequent as 0.5/per 100 patient-years, with an absolute precision of 0.1% and 95% confidence.</span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size:14px;\"><em><strong>Non-Inferiority Trial: </strong></em>The sample-size calculations are based on a non-inferiority margin of 1.46 and an expected primary annual event rate of 2% per year in the VKA arm. Study enrolment will occur over two years and all patients will be followed to a common termination at the end of an additional 2 years of follow up or for a total of about four years. Thus, the mean follow-up time will be approximately three years. Assuming 10% non-compliance to rivaroxaban in the first year with additional non-compliance of 5% per year thereafter, enrolment of 4,500 patients will give 86% power to conclude that rivaroxaban is non-inferior to VKAs or the primary outcome. If non-inferiority is established, then testing for superiority of rivaroxaban over VKA will be undertaken without statistical penalty.</span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size:14px;\"><em><strong>Superiority Trial: </strong></em>The sample-size calculations are based on an expected primary annual event rate on aspirin of 3.5%. Study enrolment will occur over two years and all patients will be followed to a common termination at the end of four years. Thus, the mean follow-up time will be approximately three years. We expect a relative risk reduction of 45% Assuming 10% non-compliance to rivaroxaban in the first year with additional non-compliance of 5% per year thereafter, enrolment of 2,000 patients will give 95% power to conclude that rivaroxaban is superior to asprin.</span></div>\n </div>\n </div>\n</div>\n<div>\n  </div>\n<p style=\"text-align: justify;\">\n  </p>\n<p style=\"text-align: justify;\">\n <br />\n  </p>\n
      • study_title<p>\n INVESTIGATION OF RHEUMATIC AF TREATMENT USING VITAMIN K ANTAGONISTS, RIVAROXABAN OR ASPRIN STUDIES</p>\n
      • laymans_summary<p>\n INVICTUS study is an international multicenter trial investigating the safety and efficacy of rivaroxaban in prevention of stroke in patients with rheumatic valvular heart disease. Rheumatic valvular heart disease is a condition in which the way through which blood passes into the heart is either narrow or leaks. This normally weakens the heart muscles and can cause abnormal heartbeats known as atrial fibrillation (AF).  Atrial fibrillation (AF) can cause blood clots in the heart, which travel to the brain. When blood clot in the heart goes to the brain, it is called stroke, symptoms may be weakness in an arm or leg, or loss of feeling or loss of ability to speak or even death. Drugs to prevent blood coagulation are used to reduce stroke in patients with atrial fibrillation. In rheumatic valvular heart disease, drugs used to prevent blood clots are called vitamin k antagonist, including warfarin or acenocoumarol or phenprocoumon. These antagonists of Vitamin K are effective in reducing stroke but difficult to use because they require regular monitoring. Recently, new drugs to prevent blood clots that are easy to use have shown to be effective in patients with atrial fibrillation but do not have rheumatic valvular heart disease. However, these new drugs have not been tested in patients with rheumatic valvular heart disease and therefore, their use in these patients has not been approved. The purpose of the Invictus study is to test if one of these new drugs, called rivaroxaban is good as a vitamin k antagonist drug for preventing stroke in patients with abnormal heartbeats (AF) and Rheumatic valvular heart disease.</p>\n<p>\n  </p>\n
      • short_titleINVICTUS
      • protocol_noECCT/16/10/01
      • version_no3.0 - 2015 -10 -19
      • date_of_protocol19-10-2015
      • study_drugRivaroxaban
      • disease_conditionRheumatic Atrial Fibrillation
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameNew Oral Anticoagulants
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameWarfarin
      • comparator_registeredYES
      • comparator_countriesArgentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Denmark, Finland, France, Great Britain, Greece, Germany, India, Israel, Italy, Kenya, Korea, Malaysia, Mexico, Netherlands, Norway, New Zealand Peru, Philippines, Russia, Spain, South Africa, Sweden, Switzerland Taiwan, Tanzania,Thailand, Turkey and Venezuela,Uganda, Ukraine, United States.
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressgituramurenga@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries1
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan0
      • applicant_contractual_agreement0
      • declaration_applicantDr. Bernard Muriuki Gitura
      • declaration_date103-10-2016
      • declaration_principal_investigatorDR. BERNARD MURIUKI GITURA
      • declaration_date203-10-2016
      • placebo_presentNo
      • study_objectives<div>\n 1 In patients with rheumatic valvular heart disease (RVHD) and who are in atrial fibrillation or flutter (AF/Flutter) and have other stroke risk factors, rivaroxaban is non-inferior to vitamin K antagonists (VKA) for prevention of stroke or systemic embolism. </div>\n<div>\n 2 In patients with RVHD either with AF/Flutter but unsuitable for VKA therapy or with sinus rhythm but with high risk, rivaroxaban is superior to aspirin for prevention of stroke or systemic embolism. </div>\n
      • principal_inclusion_criteria<div>\n <span style=\"font-size:16px;\"><u><strong>Registry:</strong></u> Any patient with RVHD diagnosed by echocardiography</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:16px;\"><u><strong>Non-Inferiority Trial:</strong></u></span></div>\n<div>\n <span style=\"font-size:16px;\">1. RVHD diagnosed by echocardiography at any time prior to enrollment</span></div>\n<div>\n <span style=\"font-size:16px;\">2. Age ≥18</span></div>\n<div>\n <span style=\"font-size:16px;\">3. Increased risk of stroke by any of the following</span></div>\n<div>\n <span style=\"font-size:16px;\">a) CHA2DS2-VASc score ≥ 2 OR</span></div>\n<div>\n <span style=\"font-size:16px;\">b) Moderate/Severe mitral stenosis with valve area ≤2.0 cm2 OR</span></div>\n<div>\n <span style=\"font-size:16px;\">c) Left atrial spontaneous echo contrast OR</span></div>\n<div>\n <span style=\"font-size:16px;\">d) Left atrial thrombus</span></div>\n<div>\n <span style=\"font-size:16px;\">4. Heart Rhythm</span></div>\n<div>\n <span style=\"font-size:16px;\">a) AF or Flutter should be documented on baseline 12-lead ECG, or on a</span></div>\n<div>\n <span style=\"font-size:16px;\">previous 12-lead ECG, Holter monitor, in-hospital ECG rhythm strip or</span></div>\n<div>\n <span style=\"font-size:16px;\">Pacemaker or ICD electrogram.</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:16px;\"><strong><u>Superiority trial</u></strong></span><br />\n <br />\n <div>\n <span style=\"font-size:16px;\">1. RVHD diagnosed by echocardiography at any time prior to enrollment</span></div>\n <div>\n <span style=\"font-size:16px;\">2. Age ≥18</span></div>\n <div>\n <span style=\"font-size:16px;\">3. Increased risk of stroke by any of the following</span></div>\n <div>\n <span style=\"font-size:16px;\">a) CHA2DS2-VASc score ≥ 2 OR</span></div>\n <div>\n <span style=\"font-size:16px;\">b) Moderate/Severe mitral stenosis with valve area ≤2.0 cm2 OR</span></div>\n <div>\n <span style=\"font-size:16px;\">c) Left atrial spontaneous echo contrast OR</span></div>\n <div>\n <span style=\"font-size:16px;\">d) Left atrial thrombus</span></div>\n <div>\n <span style=\"font-size:16px;\">4. Heart Rhythm</span></div>\n <div>\n <span style=\"font-size:16px;\">a) AF or Flutter and unsuitable for VKA therapy. (AF or Flutter should be</span></div>\n <div>\n <span style=\"font-size:16px;\">documented on baseline 12-lead ECG, or on a previous 12-lead ECG,</span></div>\n <div>\n <span style=\"font-size:16px;\">Holter monitor, in-hospital ECG rhythm strip or Pacemaker or ICD</span></div>\n <div>\n <span style=\"font-size:16px;\">electrogram) OR</span></div>\n <div>\n <span style=\"font-size:16px;\">b) In the absence of AF or Flutter, patients would be eligible in the presence</span></div>\n <div>\n <span style=\"font-size:16px;\">of any one of the following:</span></div>\n <div>\n <span style=\"font-size:16px;\">a. Left atrial enlargement ≥5.5 cm OR</span></div>\n <div>\n <span style=\"font-size:16px;\">b. Left atrial spontaneous echo contrast OR</span></div>\n <div>\n <span style=\"font-size:16px;\">c. Left atrial thrombus OR</span></div>\n <div>\n <span style=\"font-size:16px;\">d. Frequent ectopic atrial activity (>1000/24 hours) on Holter monitoring</span></div>\n</div>\n<p>\n  </p>\n
      • principal_exclusion_criteria<p>\n <span style=\"font-size:16px;\"><u><strong>Exclusion Criteria for both non-inferiority and superiority trials:</strong></u></span></p>\n<div>\n <span style=\"font-size:16px;\">1. Refusal to consent</span></div>\n<div>\n <span style=\"font-size:16px;\">2. Actively involved in any study that would compromise the protocol of</span></div>\n<div>\n <span style=\"font-size:16px;\">INVICTUS Trial</span></div>\n<div>\n <span style=\"font-size:16px;\">3. Severe co-morbid condition with life expectancy < 1 year</span></div>\n<div>\n <span style=\"font-size:16px;\">4. Other serious condition(s) or logistic factors likely to interfere with study</span></div>\n<div>\n <span style=\"font-size:16px;\">participation or with the ability to complete the trial, as appropriate to country</span></div>\n<div>\n <span style=\"font-size:16px;\">or region.</span></div>\n<div>\n <span style=\"font-size:16px;\">5. Likely to have valve replacement surgery within 6 months</span></div>\n<div>\n <span style=\"font-size:16px;\">6. Mechanical valve prosthesis or other condition requiring treatment with VKAs.</span></div>\n<div>\n <span style=\"font-size:16px;\">Patients with deep vein thrombosis or recent pulmonary embolism can be</span></div>\n<div>\n <span style=\"font-size:16px;\">enrolled where both VKAs and rivaroxaban are approved.</span></div>\n<div>\n <span style=\"font-size:16px;\">7. Contraindication to the study medication of the trial</span></div>\n<div>\n <span style=\"font-size:16px;\">a. Allergy to rivaroxaban</span></div>\n<div>\n <span style=\"font-size:16px;\">b. Allergy to VKAs ( non-inferiority trial)</span></div>\n<div>\n <span style=\"font-size:16px;\">c. Allergy to aspirin ( superiority trial)</span></div>\n<div>\n <span style=\"font-size:16px;\">8. Severe renal insufficiency with an calculated creatinine clearance (Cockcroft-</span></div>\n<div>\n <span style=\"font-size:16px;\">Gault) < 15 ml/min</span></div>\n<div>\n <span style=\"font-size:16px;\">9. Serious bleeding in the past six months or at high risk for bleeding</span></div>\n<div>\n <span style=\"font-size:16px;\">10. Moderate to severe hepatic impairment</span></div>\n<div>\n <span style=\"font-size:16px;\">11. Ongoing need for dual antiplatelet therapy (patients with on-going aspirin</span></div>\n<div>\n <span style=\"font-size:16px;\">therapy ≤100 mg per day are not excluded).</span></div>\n<div>\n <span style=\"font-size:16px;\">12. Ongoing need for dual strong inhibitors of CYP-3a4 or p-glycoprotein</span></div>\n<div>\n <span style=\"font-size:16px;\">inhibitor.</span></div>\n<div>\n <span style=\"font-size:16px;\">13. Received an investigational drug in the past 30 days</span></div>\n<div>\n <span style=\"font-size:16px;\">14. Patients considered unsuitable for trial inclusion because of unwillingness to</span></div>\n<div>\n <span style=\"font-size:16px;\">attend follow up visits</span></div>\n<div>\n <span style=\"font-size:16px;\">15. Women who are pregnant and/or breastfeeding</span></div>\n<div>\n <span style=\"font-size:16px;\">16. Women of child bearing age who do not use an effective form of birth control.</span></div>\n<div>\n  </div>\n
      • primary_end_points<div>\n <span style=\"font-size:12px;\"><u><strong>Clinical Trial Efficacy Outcomes</strong></u></span></div>\n<div>\n <span style=\"font-size:12px;\"> Assessments and procedures at occurrence of efficacy outcome events</span></div>\n<div>\n <span style=\"font-size:12px;\">Occurrence of outcomes must be reported within 3 days of the site’s notification of the</span></div>\n<div>\n <span style=\"font-size:12px;\">event. Patients are requested to inform the site as soon as possible if they are hospitalized</span></div>\n<div>\n <span style=\"font-size:12px;\">(regardless of reason) in order to ensure timely identification of potential CV events.</span></div>\n<div>\n <span style=\"font-size:12px;\">The following events will be reported on Outcome/CV Event reporting forms and</span></div>\n<div>\n <span style=\"font-size:12px;\">will undergo blinded adjudication by expert adjudicators.</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Stroke</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Systemic embolism</span></div>\n<div>\n <span style=\"font-size:12px;\">In addition to investigator identified CV events, safety data will be reviewed regularly for</span></div>\n<div>\n <span style=\"font-size:12px;\">potential CV events. In particular, Medical Dictionary for Regulatory Activities</span></div>\n<div>\n <span style=\"font-size:12px;\">(MedDRA) preferred terms assigned to investigator reported AEs will be screened for</span></div>\n<div>\n <span style=\"font-size:12px;\">potential outcome events and investigators may then be asked to further investigate</span></div>\n<div>\n <span style=\"font-size:12px;\">whether or not a CV event occurred and potentially initiate the outcomes reporting process.</span></div>\n<div>\n <span style=\"font-size:12px;\"><strong>Definition of efficacy outcome events (Primary and Secondary)</strong></span></div>\n<div>\n <span style=\"font-size:12px;\">The following Primary efficacy outcome events will be assessed and are defined in the</span></div>\n<div>\n <span style=\"font-size:12px;\">Stroke is defined as any focal neurologic deficit lasting>24 hours with or without brain</span></div>\n<div>\n <span style=\"font-size:12px;\">imaging suggestive of a primary ischemic origin leading to tissue infarction. Neuroimaging</span></div>\n<div>\n <span style=\"font-size:12px;\">evidence should be provided wherever possible. Transient ischemic attack with positive neuroimaging</span></div>\n<div>\n <span style=\"font-size:12px;\">will be considered a stroke</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:12px;\"><strong> Systemic embolism</strong></span></div>\n<div>\n <span style=\"font-size:12px;\">Systemic embolism is defined as abrupt vascular insufficiency associated with clinical or</span></div>\n<div>\n <span style=\"font-size:12px;\">radiological evidence of arterial occlusion in the absence of other likely mechanisms.</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:12px;\"><strong>Myocardial infarction</strong></span></div>\n<div>\n <span style=\"font-size:12px;\">The term acute MI is used when there is evidence of myocardial necrosis in a clinical setting</span></div>\n<div>\n <span style=\"font-size:12px;\">consistent with acute myocardial ischemia. The diagnosis of MI requires the combination of:</span></div>\n<div>\n <span style=\"font-size:12px;\">• Evidence of myocardial necrosis (either changes in cardiac biomarkers or post-mortem</span></div>\n<div>\n <span style=\"font-size:12px;\">pathological findings); and</span></div>\n<div>\n <span style=\"font-size:12px;\">• Supporting information derived from the clinical presentation, electrocardiographic</span></div>\n<div>\n <span style=\"font-size:12px;\">changes, or the results of myocardial or coronary artery imaging</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:12px;\"><strong> Vascular death</strong></span></div>\n<div>\n <span style=\"font-size:12px;\">Vascular death includes death due to stroke, myocardial infarction, heart failure or cardiogenic</span></div>\n<div>\n <span style=\"font-size:12px;\">shock, sudden death or any other death due to other cardiovascular causes. In addition, death</span></div>\n<div>\n <span style=\"font-size:12px;\">due to hemorrhage will be included.</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:12px;\"><u><strong>Clinical Safety Outcomes</strong></u></span></div>\n<div>\n <span style=\"font-size:12px;\">The safety outcomes are bleeding events using the International Society on Thrombosis and</span></div>\n<div>\n <span style=\"font-size:12px;\">Haemostasis (ISTH) major bleeding definition, and other definitions derived from these as listed in</span></div>\n<div>\n <span style=\"font-size:12px;\">Section 6.9.1 and Section 6.9.2. Bleeding events will be reported on the bleeding reporting forms</span></div>\n<div>\n <span style=\"font-size:12px;\">and exempted from SAE reporting.</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:12px;\"><em><strong>6.9.1 Primary safety variable</strong></em></span></div>\n<div>\n <span style=\"font-size:12px;\">The primary safety variable is the time from randomization to time of first occurrence of a</span></div>\n<div>\n <span style=\"font-size:12px;\">major bleeding defined as a bleeding event that meets at least one of the following criteria:</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Fatal bleeding, and/or</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Bleeding in a critical area or organ (intracranial, intraocular, intraspinal, pericardial,</span></div>\n<div>\n <span style=\"font-size:12px;\">retroperitoneal, intraarticular, or intramuscular with compartment syndrome), and/or</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Clinically overt bleeding associated with a recent decrease in the haemoglobin level of</span></div>\n<div>\n <span style=\"font-size:12px;\">more than 2 g/dL (20 g/L; 1.24 mmol/L) compared to the most recent haemoglobin</span></div>\n<div>\n <span style=\"font-size:12px;\">value available before the event, and/or</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Clinically overt bleeding leading to transfusion of 2 or more units of packed red blood</span></div>\n<div>\n <span style=\"font-size:12px;\">cells or whole blood</span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:12px;\"><em><strong>6.9.2 Secondary safety variable</strong></em></span></div>\n<div>\n <span style=\"font-size:12px;\">The secondary safety variables are the time from randomization to time of first occurrence of:</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Life-threatening bleeding, defined as a subset of major bleeding that meet at least one</span></div>\n<div>\n <span style=\"font-size:12px;\">of the following criteria:</span></div>\n<div>\n <span style=\"font-size:12px;\">o Fatal bleeding</span></div>\n<div>\n <span style=\"font-size:12px;\">o Symptomatic intracranial bleeding</span></div>\n<div>\n <span style=\"font-size:12px;\">o Reduction in haemoglobin of at least 5 g/dl (50 g/l; 3.10 mmol/L)</span></div>\n<div>\n <span style=\"font-size:12px;\">o Transfusion of at least 4 units of packed red cells or whole blood</span></div>\n<div>\n <span style=\"font-size:12px;\">o Associated with hypotension requiring the use of intravenous inotropic agents</span></div>\n<div>\n <span style=\"font-size:12px;\">o Necessitated surgical intervention</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Clinically relevant non-major bleeding, defined as non-major overt bleeding but</span></div>\n<div>\n <span style=\"font-size:12px;\">o Requires medical attention (e.g., hospitalization, medical treatment for</span></div>\n<div>\n <span style=\"font-size:12px;\">bleeding), and/orfollowing subsections of this protocol:</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Stroke </span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Systemic embolism </span></div>\n<div>\n  </div>\n<div>\n <span style=\"font-size:12px;\">The following Secondary efficacy outcome events will be assessed and are defined in the</span></div>\n<div>\n <span style=\"font-size:12px;\">following subsections of this protocol:</span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· MI </span></div>\n<div>\n <span style=\"font-size:12px;\">ï‚· Vascular death </span></div>\n<div>\n <span style=\"font-size:12px;\">Additional detailed definitions for these efficacy outcomes will be provided in a separate</span></div>\n<div>\n <span style=\"font-size:12px;\">Adjudication manual.</span></div>\n<div>\n <span style=\"font-size:12px;\"> Stroke</span></div>\n<div>\n <span style=\"font-size:12px;\">o Is associated with a study drug interruption of more than 14 days.</span></div>\n<div>\n  </div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n KENYATTA NATIONAL HOSPITAL<br />\n Professor Elijah Nyainda Ogola, MbChB, Mmed, FACC - site principal investigator<br />\n Dr. Bernard Muriuki Gitura, MbChB, Mmed, Cert C - co-principal investigator<br />\n Peninah Kinuthia- Research Coordinator<br />\n <br />\n MOI TEACHING AND REFERRAL HOSPITAL<br />\n Dr. Felix Ayub Barasa- Site Principal Investigator<br />\n Dr. Benson Njuguna- Trial Pharmacist<br />\n Samuel Anaynje- pharmaceutical Technologist<br />\n Caudencia Chepkorir-  Trial Research Nurse<br />\n <br />\n THE KAREN HOSPITAL<br />\n Dr. Anthony Gikonyo- Site Principal Investigator<br />\n Dr. Stephen Omondi- coprincipal Investigator<br />\n Dr. Christina Mulwa- Trial pharmacist<br />\n Betty Weru Trial research nurse<br />\n Fredah Mwangi Study Coordinator<br />\n Duncan Luvayo Study Coordinator</p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n 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 </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n <br />\n <br />\n  </p>\n
      • other_details_explanation<p>\n Vitamin K Antagonists (VKAs) for example Warfarin are the main drugs administered for prevention of thrombo- embolic events in patients with Rheumatic Valve Heart Disease (RVHD) with Atrila Fibrillation (AF). The limiting factor with VKAs is that they need frequent monitoring to ensure safety and  efficacy of the drug. This can be particularly difficult in developing countries. The trial hopes to establish rivaroxaban as a safe and effective alternative treatment for valvular atrial fibrillation with need for minimal monitoring.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n 1. KNH/UON ERC 28th June 2016</p>\n<p>\n 2 MOI Teaching and Referral Hospital IREC</p>\n
      • other_details_regulatory_rejected<p>\n NONE</p>\n
      • other_details_regulatory_halted<p>\n NOT APPLICABLE</p>\n
      • estimated_duration5 years
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorVitamin K antagonist
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states29
      • number_of_sites3
      • multi_country_listAngola, Botswana, Brazil, Cameroon, Ethiopia, India, Indonesia, Kazakhstan, Kenya, Kyrgyzstan, Mexico, Mozambique, Namibia, Nigeria, Pakistan, Paraguay, Philippines, Rwanda, South Africa, Sudan, Tanzania, Uganda, Zambia, Zimbabwe
      • data_monitoring_committeeYes
      • total_enrolment_per_siteKenyatta National Hospital 5 participants per month\nThe Karen Hospital 3 participants per month\nMoi Teaching and Referral Hospital 7 participants per month\n
      • total_participants_worldwide4500
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameBernard
      • investigator1_middle_nameMuriuki
      • investigator1_family_nameGitura
      • investigator1_qualificationMbChB,Mmed,Cert C
      • investigator1_professional_addressHospital Road, Box 2249 00202 KNH
      • investigator1_telephone+254717977637
      • investigator1_emailbgit27@gmail.com
      • organisations_transferred_Yes
      • number_participants250
      • notification<p>\n NOT APPLICABLE</p>\n
      • approval_date07-03-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted24-09-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n BACKGROUND Testing of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease–associated atrial fibrillation has been limited.</p>\n<p>\n METHODS We enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHA2 DS2 VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating a higher risk of stroke), a mitral-valve area of no more than 2 cm2 , left atrial spontaneous echo contrast, or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K antagonist. The primary efficacy outcome was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. We hypothesized that rivaroxaban therapy would be noninferior to vitamin K antagonist therapy. The primary safety outcome was major bleeding according to the International Society of Thrombosis and Hemostasis.</p>\n<p>\n RESULTS Of 4565 enrolled patients, 4531 were included in the final analysis. The mean age of the patients was 50.5 years, and 72.3% were women. Permanent discontinuation of trial medication was more common with rivaroxaban than with vitamin K antagonist therapy at all visits. In the intention-to-treat analysis, 560 patients in the rivaroxaban group and 446 in the vitamin K antagonist group had a primary-outcome event. Survival curves were nonproportional. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the vitamin K antagonist group (difference, −76 days; 95% confidence interval [CI], −121 to −31; P<0.001). A higher incidence of death occurred in the rivaroxaban group than in the vitamin K antagonist group (restricted mean survival time, 1608 days vs. 1680 days; difference, −72 days; 95% CI, −117 to −28). No significant between-group difference in the rate of major bleeding was noted.</p>\n<p>\n CONCLUSIONS Among patients with rheumatic heart disease–associated atrial fibrillation, vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; INVICTUS ClinicalTrials.gov number, NCT02832544.</p>\n
      • implication_results<p>\n In patients with atrial fibrillation not related to rheumatic heart disease, treatment with rivaroxaban or other factor Xa inhibitors has been shown to be noninferior to warfarin therapy for stroke prevention, with large reduction in the risk of hemorrhagic stroke.</p>\n<p>\n No evidence suggests that rivaroxaban therapy increases mortality among patients with other heart conditions. Treatment with rivaroxaban reduces mortality substantially among patients with atherosclerotic vascular disease. Thus, our data support the hypothesis that vitamin K antagonist therapy reduces the risk of death from vascular causes among patients with rheumatic heart disease; this effect appears to be independent of the prevention of atrial fibrillation–related stroke and suggests a direct effect on the disease process of rheumatic heart disease. Our trial showed that as compared with rivaroxaban, vitamin K antagonist therapy led to a lower rate of ischemic stroke among patients with rheumatic heart disease–associated atrial fibrillation and lower mortality due to vascular causes, without significantly increasing the rate of major bleeding. The results of this trial support current guidelines, which recommend vitamin K antagonist therapy for the prevention of stroke in patients with rheumatic heart disease in whom atrial fibrillation develops</p>\n<p>\n  </p>\n
      • quantity_imported
      • quantity_dispensed
      • quantity_destroyed
      • quantity_exported
      • balance_site
      • final_date0000-00-00
      • modified2023-02-19 18:46:08
      • created2016-09-04 19:24:59
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id355
        • application_id552
        • given_nameElijah
        • middle_nameNyainda
        • family_nameOgola
        • qualificationMbChB,Mmed, FACC
        • professional_addressP.O. BOX 19676- 00202 NAIROBI
        • telephone+254 (0) 723174268
        • emailelijah.ogola@uonbi.ac.ke
        • created2016-09-04 19:46:40
        • modified2020-09-24 09:01:22
      • 1(array)
        • id363
        • application_id552
        • given_namefelix
        • middle_nameayub
        • family_namebarasa
        • qualificationMbChB, Mmed
        • professional_addressP.O. BOX 8584-30100 ELDORET
        • telephone+254 723 174 268
        • emailbarasaceo12@gmail.com
        • created2016-10-03 11:28:35
        • modified2020-09-24 09:01:22
    • SiteDetail(array)
      • 0(array)
        • id422
        • application_id552
        • county_id47
        • site_nameKenyatta National hospital
        • physical_addressHospital Road
        • contact_detailsBox 20723 00202, Tel 726300
        • contact_personDr Bernard Gitura
        • site_capacity(null)
        • misc(null)
        • created2016-09-04 19:46:40
        • modified2020-09-24 09:01:22
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id423
        • application_id552
        • county_id27
        • site_nameMoi teaching and Referral Hospital
        • physical_addressNandi Road, Eldoret
        • contact_detailsP.O. Box 3-30100 Eldoret, +254 (053)2061749
        • contact_personDr Felix Ayub Barasa
        • site_capacity(null)
        • misc(null)
        • created2016-09-04 21:46:07
        • modified2020-09-24 09:01:22
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
      • 2(array)
        • id425
        • application_id552
        • county_id47
        • site_nameThe Karen Hospital
        • physical_addressLangata Road - Karen
        • contact_detailsP.O. Box 74240- 00200 Nairobi, +254 (0)20 661300
        • contact_personDr Anthony Gikonyo
        • site_capacity(null)
        • misc(null)
        • created2016-09-04 21:46:07
        • modified2020-09-24 09:01:22
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id283
        • application_id552
        • sponsorHamilnton Health sciences, hamilnton,ON, Canada
        • sponsor_typeResearch Institution
        • contact_person
        • address237 Barton Street East, Hamilton,Ontario, Canada L8L 2X2
        • telephone_number905 527 4322 ext 40596
        • fax_number
        • cell_number905 527 4322 ext 40596
        • email_addressinvictus@phri.ca
        • created2016-09-04 19:46:40
        • modified2020-09-24 09:01:22
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(array)
    • approved1
• $this->validationErrors(array)
  • Permission(empty)
  • Aro(empty)
  • Aco(empty)
  • Application(empty)
  • User(empty)
  • TrialStatus(empty)
  • InvestigatorContact(empty)
  • Sponsor(empty)
  • SiteDetail(empty)
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  • 1Form
  • 2Session
  • 3Text
  • 4Number
  • 5SimpleGraph
  • 6Paginator
  • 7DebugTimer
  • 8Toolbar
  • 9HtmlToolbar

App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

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

Included Files

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