[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100532402":3},{"organization":4,"outcomesModule":7,"designInfo":109,"detailedDescription":122,"studyPopulation":114,"armGroups":123,"interventions":155,"overallOfficials":174,"centralContacts":187,"locations":196,"responsibleParty":267,"collaborators":269,"id":301,"slug":302,"hasResults":303,"nctId":304,"briefTitle":305,"officialTitle":306,"acronym":114,"eligibilityCriteria":307,"healthyVolunteers":303,"sex":308,"minAge":309,"maxAge":114,"enrollmentInfo":310,"targetDuration":114,"studyType":313,"phases":314,"briefSummary":317,"conditions":318,"keywords":320,"overallStatus":217,"whyStopped":114,"lastUpdateSubmitDate":326,"lastUpdatePostDateStruct":327,"startDateStruct":330,"completionDateStruct":332,"leadSponsor":334,"locationsCount":335},{"fullName":5,"class":6},"Irrua Specialist Teaching Hospital","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":23,"otherOutcomes":105},[9,13,17,20],{"measure":10,"description":11,"timeFrame":12},"Death","Proportion of participants death definition by Y\u002FN measure\n\nClinical aggravation is defined as the first occurrence of one of the following conditions, at any time point between baseline and Day 14 (included):\n\nDeath, or\n\nIncrease (+1 or +2) in the number (0, 1 or 2) of organ failures among:\n\nRenal failure: KDIGO stage 3 Respiratory failure: SpO2\u002FFiO2\\* ≤ 315 Cardiovascular failure: MBP\\*\\* \\\u003C 65 mmHg or SBP \\\u003C 90 mmHg (measured twice with a time interval of 10 min) and lactate \\> 2 mmol\u002FL Analysis per component Proportion of participants with a newly occurring component of the composite primary endpoint between Day 0 and Day 14.\n\nSensitivity analyses Proportion of participants presenting no clinical aggravation between baseline and Day 14, with varying thresholds on the definitions of organ failures or adding different organ failures definition (e.g. neurologic, hepatic, hematologic, etc.).","Day 28",{"measure":14,"description":15,"timeFrame":16},"New onset of acute kidney failure","Proportion of participants a new onset of acute kidney failure . Definition by KDIGO 3 measure. 3.0 times baseline, OR increase in serum creatinine to ≥4.0 mg\u002Fdl (≥353.6 mmol\u002Fl).\n\nThe composite endpoint assesses the new onset of an event from D0","Between Day 0 and Day 10",{"measure":18,"description":19,"timeFrame":16},"New onset of acute respiratory failure","Proportion of participants a new onset of acute respiratory failure. Definition by SpO2\u002FFiO2 ≤ 315 measure The composite endpoint assesses the new onset of an event from D0",{"measure":21,"description":22,"timeFrame":16},"New onset of shock","Proportion of participants a New onset of shock. Mean Blood Pressure (MBP) \\\u003C 65 mmHg or Systolic Blood Pressure (SBP) \\\u003C 90 mmHg (measured twice with a time interval of 10 min) and lactate \\> 2 mmol\u002FL measured at the same time The composite endpoint assesses the new onset of an event from D0",[24,27,30,33,37,41,44,47,50,53,56,59,62,65,69,73,77,80,82,84,86,88,90,93,95,99,102],{"measure":25,"description":26,"timeFrame":16},"Safety of each IMP and SCD","Proportion (events and participants with at least one event) of:\n\n* Adverse Event\\* grade 3 and higher\n* Serious Adverse Event\n* Adverse Event of Special Interest",{"measure":25,"description":28,"timeFrame":29},"Proportion (events and participants with at least one event) of:\n\nAdverse Event\\* grade 3 and higher\n\n* Serious Adverse Event\n* Adverse Event of Special Interest","Day 0, Day 28",{"measure":31,"description":32,"timeFrame":16},"Organ failure from composite primary endpoint","Proportion of participants with a newly occurring component of the composite primary endpoint",{"measure":34,"description":35,"timeFrame":36},"New onset of Acute Kidney Injury","Proportion of participants meeting KDIGO ≥ 2 or initiation of renal replacement therapy parameters","Between Day 0 and discharge",{"measure":38,"description":39,"timeFrame":40},"New onset of CVPU or seizure","Proportion of participants with CVPU or seizure","Between Day 0 and Discharge",{"measure":42,"description":43,"timeFrame":40},"New onset of Bleeding","Proportion of participants meeting WHO bleeding scale grade 2 or above",{"measure":45,"description":46,"timeFrame":40},"New onset of Severe anaemia","Proportion of participants with Hb level \\\u003C 8 g\u002FdL",{"measure":48,"description":49,"timeFrame":40},"New onset of liver failure","Proportion of participants with AST or ALT ≥ 3 ULN",{"measure":51,"description":52,"timeFrame":40},"New onset of clinical severity score","Proportion of participants with a NEWS2 score ≥7",{"measure":54,"description":55,"timeFrame":40},"Intensive care strategies - oxygen therapy","Proportion of participants having received oxygen therapy",{"measure":57,"description":58,"timeFrame":40},"Intensive care strategies - RRT","Proportion of participants having received RRT",{"measure":60,"description":61,"timeFrame":40},"Intensive care strategies - blood transfusion","Proportion of participants having received blood transfusion",{"measure":63,"description":64,"timeFrame":40},"Intensive care strategies- inotropes or vasopressors","Proportion of participants having received inotropes or vasopressors",{"measure":66,"description":67,"timeFrame":68},"the viral clearance - Change in LF RT-PCR Ct","value (for each target gene) from D0","Day 3, Day 5, Day 7, Day 9",{"measure":70,"description":71,"timeFrame":72},"the viral clearance - Change in LASV viral","titer from D0","D01-D10",{"measure":74,"description":75,"timeFrame":76},"viral clearance - LASV RT-PCR","\\\u003CLLQ","D01- D10",{"measure":78,"description":79,"timeFrame":16},"Pharmacokinetics (phase II only)","• Peak concentration (Cmax)",{"measure":78,"description":81,"timeFrame":16},"• Time to peak concentration (Tmax)",{"measure":78,"description":83,"timeFrame":16},"• Area under the curve",{"measure":78,"description":85,"timeFrame":16},"• Half-life",{"measure":78,"description":87,"timeFrame":16},"• Clearance",{"measure":78,"description":89,"timeFrame":16},"• Volume(s) of distribution",{"measure":91,"description":92,"timeFrame":16},"PK\u002FPD (phase II only)","• Prediction of initial viral load and slope of decline",{"measure":91,"description":94,"timeFrame":16},"• Optimal dosing regimen with PK\u002FPD modelling",{"measure":96,"description":97,"timeFrame":98},"LASV RT-PCR","LASV RT-PCR (Ct value)","D28 if participants have a positive RT PCR at discharge",{"measure":100,"description":101,"timeFrame":72},"Peak CRP (Phase II stage only)","Peak CRP level (mg\u002FL)",{"measure":103,"description":104,"timeFrame":72},"Time to first LASV RT-PCR \u003CLLOQ","Time to first LASV RT-PCR \\\u003CLLOQ (days)",[106],{"measure":107,"description":108,"timeFrame":16},"Viral resistance parameters","Frequency of LASV resistance mutations",{"allocation":110,"interventionModel":111,"interventionModelDescription":112,"primaryPurpose":113,"observationalModel":114,"timePerspective":114,"maskingInfo":115},"RANDOMIZED","SEQUENTIAL","a) Arms\n\nIntervention\u002F treatement\n\nArm 1: SCD: ribavirin Arm:2 Favirpiravir 1600 Arm 3: Favipiravir 1200+ribavirin Arm 4: Ribavirin + dexamethasone Arm 5: ARN-75039 high dose (100) Arm 6: ARN-75039 low dose (50)","TREATMENT",null,{"masking":116,"maskingDescription":117,"whoMasked":118},"TRIPLE","Participant, Investigator, Outcomes Assessor",[119,120,121],"PARTICIPANT","INVESTIGATOR","OUTCOMES_ASSESSOR","The INTEGRATE study is a platform, multinational, multicentre, sequential, seamless phase II-III, controlled, randomised, superiority trial in open-label parallel arms. Three arms will be assessed and compared to the SCD. Its primary objective is to compare the efficacy of each Investigational Medical Product (IMP) to Standard of Care Drug (SCD) to prevent death or organ failure in hospitalized patients with confirmed LF. Secondary objectives will be i) to compare the safety and tolerability of each IMP and SCD, ii) to compare the efficacy of each IMP and SCD on clinical, virological and biological parameters, iii) to describe the pharmacokinetics of each IMP and iv) to develop a pharmacokinetics \u002F pharmacodynamics model for each IMP informing about optimal dosing regimens and dose-response relationship.\n\n1. Objectives\n\n   1.1 Primary objective The primary objective of the trial is to compare the efficacy of each IMP and SCD to prevent death or organ failure in hospitalized participants with confirmed LF.\n\n   1.2. Secondary objectives\n   * To compare the safety and tolerability of each IMP and SCD\n   * To compare the efficacy of each IMP and SCD on clinical, virological and biological parameters\n   * To describe the pharmacokinetics of each IMP\n   * To develop a pharmacokinetics \u002F pharmacodynamics model for each IMP informing about optimal dosing regimens and dose-response relationship\n2. Design\n\n   * Phase II: comparative controlled design\n   * Phase III: Whitehead's sequential double triangular design\n3. Sample size:\n\n   In the current version of the protocol (if all sub-protocols start at once):\n   * 3 IMPs go into phase III: N= 732\n   * 2 IMPs go into phase III: N= 585\n   * 1 IMP go into phase III: N= 438\n4. Duration\n\n   * Hospitalization: 10 days\n   * Follow-up: 28 days",[124,130,135,140,145,150],{"label":125,"type":126,"description":127,"interventionNames":128},"Favipiravir 1600","EXPERIMENTAL","Oral favipiravir: 2400 mg BID D1; 1600 mg BID D2-D10",[129],"Drug: Favipiravir",{"label":131,"type":132,"description":133,"interventionNames":134},"Ribavirin","ACTIVE_COMPARATOR","Intravenous ribavirin (Irrua regimen - 100 mg\u002Fkg Day 1 (dose is divided: 2\u002F3 stat, 1\u002F3 8 hours later, maximum dose is 7g\u002Fday) then 25 mg\u002Fkg single dose days 2-7, 12.5 mg\u002Fkg single dose days 8-10).",[129],{"label":136,"type":126,"description":137,"interventionNames":138},"Favipiravir 1200 + ribavirin","Oral favipiravir: 2400 mg BID D1; 1200 mg BID D2-D10 Intravenous ribavirin (Irrua regimen - 100 mg\u002Fkg Day 1 (dose is divided: 2\u002F3 stat, 1\u002F3 8 hours later, maximum dose is 7g\u002Fday) then 25 mg\u002Fkg single dose days 2-7, 12.5 mg\u002Fkg single dose days 8-10).",[129,139],"Drug: Ribavirin",{"label":141,"type":126,"description":142,"interventionNames":143},"Ribavirin + dexamethasone","IV ribavirin, Irrua regimen IV or oral dexamethasone 6mg\u002Fday (For the first 48 hours, dexamethasone will be given intravenously (i. Afterwards, a switch to oral dexamethasone (same dosage) is permitted at the discretion of the study physician.)",[139,144],"Drug: Dexamethasone",{"label":146,"type":126,"description":147,"interventionNames":148},"ARN-75039 high dose","• ARN-75039 high dose\n\n* D1: 300mg (morning), 200mg (evening)\n* D2: 200mg BID\n* D3-10: 100mg BID",[149],"Drug: ARN-75039 high dose",{"label":151,"type":126,"description":152,"interventionNames":153},"ARN-75039 low dose","• ARN-75039 low dose\n\n* D1: 150mg (morning), 100mg (evening)\n* D2: 100mg BID\n* D3-10: 50mg BID",[154],"Drug: ARN-75039 low dose",[156,161,166,169,172],{"type":157,"name":158,"description":159,"armGroupLabels":160,"otherNames":114},"DRUG","Favipiravir","Interventional Medicinal Product (IMP)",[136,125,131],{"type":157,"name":131,"description":162,"armGroupLabels":163,"otherNames":164},"Control arm",[136,141],[165],"Standard of care",{"type":157,"name":167,"description":159,"armGroupLabels":168,"otherNames":114},"Dexamethasone",[141],{"type":157,"name":146,"description":170,"armGroupLabels":171,"otherNames":114},"Investigational Medicinal Product",[146],{"type":157,"name":151,"description":170,"armGroupLabels":173,"otherNames":114},[151],[175,179,183],{"name":176,"affiliation":177,"role":178},"Marie MD JASPARD, MD","ALIMA - The Alliance for International Medical Action - Paris, France","STUDY_DIRECTOR",{"name":180,"affiliation":181,"role":182},"Sylvanus OKOGBENIN, MD","Irrua Specialist Teaching Hospital Irrua - Edo State, Nigeria","PRINCIPAL_INVESTIGATOR",{"name":184,"affiliation":185,"role":186},"Michael RAMHARTER, MD","Bernhard Nocht Institute for Tropical Medicine Bernhard-Nocht-Hamburg, Germany","STUDY_CHAIR",[188,193],{"name":189,"role":190,"phone":191,"phoneExt":114,"email":192},"Camille FRITZELL, PHD","CONTACT","+33 6 58 80 90 12","camille.fritzell@coral.alima.ngo",{"name":194,"role":190,"phone":191,"phoneExt":114,"email":195},"Sylvain JUCHET","sylvain.juchet@coral.alima.ngo",[197,216,234,249],{"facility":198,"status":199,"city":200,"state":201,"zip":114,"country":202,"countryCode":203,"cosmosGeoPoint":204,"geoPoint":209,"contacts":210},"Phebe Hospital","NOT_YET_RECRUITING","Suacoco","Bong County","Liberia","LR",{"type":205,"coordinates":206},"Point",[207,208],-9.58076,6.98992,{"lat":208,"lon":207},[211,215],{"name":212,"role":190,"phone":213,"phoneExt":114,"email":214},"Minnie Sankawulo-Ricks, Doctor","+231886 523 973","msricks126@gmail.com",{"name":212,"role":182,"phone":114,"phoneExt":114,"email":114},{"facility":5,"status":217,"city":218,"state":219,"zip":114,"country":220,"countryCode":221,"cosmosGeoPoint":222,"geoPoint":226,"contacts":227},"RECRUITING","Irrua","Edo","Nigeria","NG",{"type":205,"coordinates":223},[224,225],6.21984,6.73634,{"lat":225,"lon":224},[228,232],{"name":229,"role":190,"phone":230,"phoneExt":114,"email":231},"Sylvanus Okogbenin, Professor","+2348060476179","okogbenins@yahoo.com",{"name":233,"role":182,"phone":114,"phoneExt":114,"email":114},"Cyril Erameh, Medical doctor",{"facility":235,"status":217,"city":236,"state":237,"zip":114,"country":220,"countryCode":221,"cosmosGeoPoint":238,"geoPoint":242,"contacts":243},"Federal Medical Center Owo","Owo","Ondo State",{"type":205,"coordinates":239},[240,241],5.58681,7.1962,{"lat":241,"lon":240},[244,248],{"name":245,"role":190,"phone":246,"phoneExt":114,"email":247},"Oladele Oluwafemi Ayodeji, Medical doctor","+2348035767632","femiayodeji@yahoo.com",{"name":245,"role":182,"phone":114,"phoneExt":114,"email":114},{"facility":250,"status":199,"city":251,"state":114,"zip":114,"country":220,"countryCode":221,"cosmosGeoPoint":252,"geoPoint":256,"contacts":257},"Abubakar Tafawa Balewa University Teaching Hospital","Bauchi",{"type":205,"coordinates":253},[254,255],9.84388,10.31032,{"lat":255,"lon":254},[258,262,266],{"name":259,"role":190,"phone":260,"phoneExt":114,"email":261},"Yusuf Jibrin, Professor","+2348033940611","ybjibrin@yahoo.co.uk",{"name":263,"role":190,"phone":264,"phoneExt":114,"email":265},"Ibrahim Mahmood Maigari, Doctor","+2348061551992","immaigari@atbu.edu.ng",{"name":259,"role":182,"phone":114,"phoneExt":114,"email":114},{"type":268,"investigatorFullName":114,"investigatorTitle":114,"investigatorAffiliation":114,"oldNameTitle":114,"oldOrganization":114},"SPONSOR",[270,272,274,277,280,282,285,287,289,291,293,295,297,299],{"name":271,"class":6},"Alliance for International Medical Action",{"name":273,"class":6},"University of Bordeaux",{"name":275,"class":276},"Bernhard Nocht Institute for Tropical Medicine","OTHER_GOV",{"name":278,"class":279},"Federal Medical Centre, Owo","INDUSTRY",{"name":281,"class":6},"Programme PAC-CI, Site ANRS-MIE de Côte d'Ivoire",{"name":283,"class":284},"Fondation pour la Recherche Scientifique, Benin","UNKNOWN",{"name":286,"class":6},"Médecins Sans Frontières, Belgium",{"name":288,"class":6},"Alex Ekwueme Federal University Teaching Hospital",{"name":290,"class":284},"Donka Hospital, Conakry",{"name":292,"class":6},"Centre de Recherche Médicale de Lambaréné",{"name":294,"class":6},"University of Hamburg-Eppendorf",{"name":296,"class":284},"Phebe Hospital, Liberia",{"name":298,"class":6},"University of North Carolina",{"name":300,"class":276},"ANRS, Emerging Infectious Diseases","100532402","phase-2-isthanrs-0409s-integrate-lassa-fever-study-100532402",false,"NCT06212336","ISTH\u002FANRS 0409s INTEGRATE Lassa Fever Study","Efficacy, Tolerability and Safety of New or Repurposed Drugs Against Lassa Fever in West African Countries","1. General\n\n   Inclusion criteria\n   * Clinical disease with signs and symptoms suggestive for LF\n   * Positive plasma LASV RT-PCR\n   * Participant requires hospitalization per the local guidelines\n   * Participant or their legally authorized representative is able and willing to sign the informed consent\n\n   Exclusion criteria\n   * Unwilling to provide informed consent\n   * Positive pregnancy test\n   * Unwilling to provide informed consent\n   * History of allergic reaction or other contra-indication to ribavirin according to the Reference safety document\n   * Received drug therapy for Lassa fever (excluding supportive care) prior to inclusion\n   * Has received a vaccine against LF\n2. Sub-protocols\n\n   2.1 Favipiravir high dose sub-protocol\n\n   Inclusion criteria • Age ≥ 18 years old\n\n   Exclusion criteria • Pregnancy (evidenced by positive urine pregnancy test in women of child-bearing potential)\n   * Treatment contraindicated with favipiravir according to the Reference safety document\n   * Pre-existing liver failure\n   * Severe symptomatic gout\u002Fhyperuricemia\n   * History of QT prolongation or arrhythmia or other cardiac disorders\n   * PR interval ≥ 200 ms\n   * Hypersensitivity to excipients\n   * Inability to take oral drug (e.g. encephalopathy, severe vomiting)\n\n   2.2. Favipiravir-Ribavirin sub-protocol\n\n   Inclusion criteria\n\n   • Age ≥ 18 years old\n\n   Exclusion criteria\n   * Pregnancy (evidenced by positive urine pregnancy test in women of child-bearing potential)\n   * Treatment contraindicated with favipiravir according to the Reference safety document\n   * Pre-existing liver failure\n   * Severe symptomatic gout\u002Fhyperuricemia\n   * History of QT prolongation or arrhythmia or other cardiac disorders\n   * PR interval ≥ 200 ms\n   * Hypersensitivity to excipients\n   * Inability to take oral drug (e.g. encephalopathy, severe vomiting)\n\n   2.3. Dexamethasone sub-protocol\n\n   Inclusion criteria • Age ≥ 12 years old\n\n   Exclusion criteria\n\n   • Pregnancy (evidenced by positive urine pregnancy test in women of child-bearing potential)\n\n   • Known intolerance and contra-indications to ribavirin or dexamethasone\n\n   • Patients who already received a corticosteroid within the preceding 7 days\n\n   2.4 ARN-75039 subprotocols\n\n   Exclusion criteria • History of severe gastrointestinal disease\n\n   • History of chronic generalized pruritus\n   * History of severe chronic liver disease\n   * History of severe cardiac disorder","ALL","18 Years",{"count":311,"type":312},1755,"ESTIMATED","INTERVENTIONAL",[315,316],"PHASE2","PHASE3","Lassa fever (LF) is a viral haemorrhagic fever responsible of 5000 deaths per year in West Africa, with in-hospital mortality at 12%. Transmission to humans occurs mainly via direct or indirect exposure to excreta from the rodent reservoir, mainly made up of Mastomys natalensis . Less frequently, LASV may also be transmitted from human to human and cause nosocomial outbreaks. Ribavirin is the only treatment available with worrying toxicity, questionable efficacy and low access because of its high cost. Consequently, there is an urgent need for new drugs to treat LF patients. The Research and Development (R\\&D) Blueprint of the World Health Organization (WHO) has included LF in the list of priority diseases for urgent research and development.\n\nThe INTEGRATE consortium is an unprecedented international collaboration on Lassa fever of 15 partners from 10 countries across West Africa, Europe and North America and across several disciplines (epidemiological researchers, social scientists, medical health facility professionals, humanitarian actors, etc.).",[319],"Lassa Fever",[321,322,323,324,325],"emerging infectious diseases","viral hemorrhagic fever","AFRICA","adult","adolescent","2026-02-02",{"date":328,"type":329},"2026-02-04","ACTUAL",{"date":331,"type":329},"2025-05-02",{"date":333,"type":312},"2027-06",{"name":5,"class":6},4]