Efficacy and Safety Evaluation of Treatment Regimens in Adult COVID-19 Patients in Senegal

Study Overview
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Brief Summary
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COVID-19 is an emerging pandemic disease affecting most countries including Senegal, caused by the new coronavirus (SARS-CoV-2) which was first detected in the city of Wuhan in China in December 2019. A rapid spread of the disease has occurred at a global scale, associated with a mortality rate of 3.4%. The first case in Africa was declared on February 15, 2020 in Egypt and the first case in Senegal was declared on March 2nd, 2020. In this context, the SEN-CoV-Fadj clinical trial aims to evaluate efficacy and safety, among adults, of different therapeutic regimens considered optimal according to current knowledge, as well as available and adapted to Sub-Saharan Africa. This trial is nested into a cohort of confirmed cases of COVID-19 in Senegal aiming to understand the main clinical, biological, virologic and immunological characteristics of the infection. The protocol of the cohort is based and adapted from the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) / World Health Organization (WHO) Clinical Characterisation Protocol (CCP). The Nafamostat mesilate, whose antiviral, anticoagulant an anti-inflammatory activities have been shown, has been eligible for SEN-CoV-Fadj for the treatment of moderate to severe COVID-19 cases.

Detailed Description
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COVID-19 is an emerging pandemic disease affecting most countries including Senegal, caused by the new coronavirus (SARS-CoV-2) which was first detected in the city of Wuhan in China in December 2019. A rapid spread of the disease has occurred at a global scale, associated with a mortality rate of 3.4%. The first case in Africa was declared on February 15, 2020 in Egypt and the first case in Senegal was declared on March 2nd, 2020. In this context, the SEN-CoV-Fadj clinical trial aims to evaluate efficacy and tolerance, among adults, of different therapeutic options considered optimal according to current knowledge, as well as available and adapted to Sub-Saharan Africa. This trial is nested into a cohort of confirmed cases of COVID-19 in Senegal aiming to understand the main clinical, biological, virologic and immunological characteristics of the infection. The protocol of the cohort is based and adapted from the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) / World Health Organization (WHO) Clinical Characterisation Protocol (CCP). The Nafamostat mesilate, whose antiviral, anticoagulant an anti-inflammatory activities have been shown, has been eligible for SEN-CoV-Fadj for the treatment of moderate to severe COVID-19 cases. Its efficacy and safety will be evaluated against the standard of care used in Senegal. The primary objective is to : Evaluate and compare viral clearance between the different therapeutic interventions. The secondary objectives are to: Evaluate and compare efficacy of the different therapeutic regimens Evaluate and compare the tolerance of the different therapeutic regimens Evaluate and compare the impact of the different therapeutic interventions on the length of hospitalization and other clinical measurements

Official Title
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Multicentre, Open Label, Randomised, Adaptative Clinical Trial of Efficacy and Safety of Treatment Regimens in Adult COVID-19 Patients in Senegal

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Nafamostat Mesilate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed cases of SARS-CoV-2 infection hospitalized in reference services identified by the Ministry of Health and Social Action of Senegal Adults (≥18 years) Full understanding and consent to participate to the trial No contraindications to taking the tested treatments Clinical status from 3 to 5 on the seven-category ordinal scale Pneumonia highlighted by infiltration of the lungs by chest CT scan or chest radiography Absence of contraindications to radiographic examinations (X-ray and/or CT scan) for diagnosis and/or follow-up Inclusion in the 72 hours following the radiological pneumonia confirmation Non-inclusion Criteria: Pregnant or breastfeeding woman Patient at high risk of death within 3 days of inclusion, in the clinician's opinion Corrected QT interval (QTc) >500ms Heart electrical dysfunction: atrioventricular block Mobitz type II second-degree, high-grade or complete without a functioning pacemaker Uncontrolled and clinically significant heart diseases, such as arrhythmia, angina or decompensated congestive heart failure Kidney failure (Cl < 30 mL/min) Patients with liver cirrhosis whose Child-Puch score is B or C Patients who have liver disease abnormalities with ALT or AST > 5 times ULN Patients who have a known HIV status Patients who have other clinically-important diseases in decompensation which may interfere with the evaluation or completion of the tested treatment's procedure, in the clinician's opinion Patients with a clinical or psychological condition which, in the clinician's opinion, does not allow adequate evaluation of the tested treatment Known allergy to the studied treatment regimen Other contraindications with the studied treatment regimen Known drug-drug interaction with a treatment usually taken by the participant contraindicating one of the studied treatment regimen

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of Care<br>The Standard of Care is the treatment which is the most adapted to the patient in the clinician's opinion. It could include the combination of Hydroxychloroquine and Azithromycin in the absence of contraindication. | |
| Experimental: Standard of Care + Nafamostat mesilate<br>The Standard of Care is the treatment which is the most adapted to the patient in the clinician's opinion. It could include the combination of Hydroxychloroquine and Azithromycin in the absence of contraindication. Nafamostat mesilate | Drug: Nafamostat Mesilate<br>* Nafamostat mesilate continuous intravenous injection. Daily dose ranging between 0.1 mg/kg/h and 0.2 mg/kg/h, based on the severity and underlying disease of the clinical trial participant. Administration for 10-14 days based on the severity and underlying disease of the clinical trial participant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SARS-CoV-2 viral load level | Real time-PCR (RT-PCR) result of the naso- and oro-pharyngeal sample | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vital status |  | Day 15 | 
| Proportion of patients with serious adverse events reported during the clinical trial. |  | through study completion, an average of 7 months | 
| Length of hospitalization |  | through hospitalization, an average of 2 weeks | 
| Length of hospitalization in a resuscitation unit |  | through hospitalization, an average of 2 weeks | 
| Duration of oxygen therapy |  | through hospitalization, an average of 2 weeks | 
| Maximum quick SOFA (qSOFA) score during hospitalisation |  | through hospitalization, an average of 2 weeks | 
| Clinical status on the seven-category ordinal scale | not hospitalized with resumption of normal activities; not hospitalized, but unable to resume normal activities; hospitalization, not requiring supplemental oxygen; hospitalization, requiring supplemental oxygen; hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation; hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; death. | through hospitalization, an average of 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, SARS-CoV-2, Efficacy, Safety, Senegal, Nafamostat mesilate