ISTH/ANRS 0409s INTEGRATE Lassa Fever Study
ConditionLassa Fever
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorIrrua Specialist Teaching Hospital
About this trial
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.
The 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.).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
General
Clinical disease with signs and symptoms suggestive for LF
Positive plasma LASV RT-PCR
Participant requires hospitalization per the local guidelines
Disqualifiers
Unwilling to provide informed consent
Positive pregnancy test
Unwilling to provide informed consent
History of allergic reaction or other contra-indication to ribavirin according to the Reference safety document
Trial design
Design model
Sequential
Treatments tested in this trial
Favipiravir
DrugInterventional Medicinal Product (IMP)
Ribavirin
DrugControl arm
Dexamethasone
DrugInterventional Medicinal Product (IMP)
ARN-75039 high dose
DrugInvestigational Medicinal Product
ARN-75039 low dose
DrugInvestigational Medicinal Product
Treatment groups
1,755 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Group A: Favipiravir 1600Experimental treatment 1 intervention
Group B: RibavirinActive comparator 1 intervention
Group C: Favipiravir 1200 + ribavirinExperimental treatment 2 interventions
Group D: Ribavirin + dexamethasoneExperimental treatment 2 interventions
Group E: ARN-75039 high doseExperimental treatment 1 intervention
Group F: ARN-75039 low doseExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Death
Proportion of participants death definition by Y/N measure Clinical aggravation is defined as the first occurrence of one of the following conditions, at any time point between baseline and Day 14 (included): Death, or Increase (+1 or +2) in the number (0, 1 or 2) of organ failures among: Renal failure: KDIGO stage 3 Respiratory failure: SpO2/FiO2\* ≤ 315 Cardiovascular failure: MBP\*\* \< 65 mmHg or SBP \< 90 mmHg (measured twice with a time interval of 10 min) and lactate \> 2 mmol/L Analysis per component Proportion of participants with a newly occurring component of the composite primary endpoint between Day 0 and Day 14. Sensitivity 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.).
Time frame
Day 282
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/dl (≥353.6 mmol/l). The composite endpoint assesses the new onset of an event from D0
Time frame
Between Day 0 and Day 103
New onset of acute respiratory failure
Proportion of participants a new onset of acute respiratory failure. Definition by SpO2/FiO2 ≤ 315 measure The composite endpoint assesses the new onset of an event from D0
Time frame
Between Day 0 and Day 104
New onset of shock
Proportion of participants a New onset of shock. Mean Blood Pressure (MBP) \< 65 mmHg or Systolic Blood Pressure (SBP) \< 90 mmHg (measured twice with a time interval of 10 min) and lactate \> 2 mmol/L measured at the same time The composite endpoint assesses the new onset of an event from D0
Time frame
Between Day 0 and Day 10Secondary outcomes
1
Safety of each IMP and SCD
Proportion (events and participants with at least one event) of: * Adverse Event\* grade 3 and higher * Serious Adverse Event * Adverse Event of Special Interest
Time frame
Between Day 0 and Day 102
Safety of each IMP and SCD
Proportion (events and participants with at least one event) of: Adverse Event\* grade 3 and higher * Serious Adverse Event * Adverse Event of Special Interest
Time frame
Day 0, Day 283
Organ failure from composite primary endpoint
Proportion of participants with a newly occurring component of the composite primary endpoint
Time frame
Between Day 0 and Day 104
New onset of Acute Kidney Injury
Proportion of participants meeting KDIGO ≥ 2 or initiation of renal replacement therapy parameters
Time frame
Between Day 0 and dischargeOther outcomes
1
Viral resistance parameters
Frequency of LASV resistance mutations
Time frame
Between Day 0 and Day 10Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Irrua Specialist Teaching Hospital
Lead sponsor
Alliance for International Medical Action
Collaborator
University of Bordeaux
Collaborator
Bernhard Nocht Institute for Tropical Medicine
Collaborator
Federal Medical Centre, Owo
Collaborator
Programme PAC-CI, Site ANRS-MIE de Côte d'Ivoire
Collaborator
Fondation pour la Recherche Scientifique, Benin
Collaborator
Médecins Sans Frontières, Belgium
Collaborator
Alex Ekwueme Federal University Teaching Hospital
Collaborator
Donka Hospital, Conakry
Collaborator
Centre de Recherche Médicale de Lambaréné
Collaborator
University of Hamburg-Eppendorf
Collaborator
Phebe Hospital, Liberia
Collaborator
University of North Carolina
Collaborator
ANRS, Emerging Infectious Diseases
Collaborator
Source ClinicalTrials.gov