Efficacy and Safety Evaluation of Treatment Regimens in Adult COVID-19 Patients in Senegal (SEN-CoV-Fadj)

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

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.

Study Overview

• Status: Unknown
• Conditions: COVID-19
• Intervention / Treatment: Drug: Nafamostat Mesilate

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 186
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Fabien Taieb, MD, PhD; Phone Number: 00221770979235; Email: Fabien.taieb@pasteur.sn
• Study Contact Backup: Name: Moussa Seydi, MD; Phone Number: 002218691881; Email: seydim@u.washington.edu

Study Locations

• Senegal
  • Dakar, Senegal
    • Recruiting
    • Infectious and Tropical Diseases Department, Fann Hospital
    • Contact: Moussa Seydi, MD; Phone Number: 002218691881; Email: seydim@u.washington.edu
    • Contact: Aissatou Lakhe, MD; Phone Number: 00221775417301; Email: aissatoulakhe@gmail.com
    • Sub-Investigator: Khardiata D. Mbaye, MD
    • Sub-Investigator: Aissatou Lakhe, MD
    • Sub-Investigator: Pape S. Ba, MD
    • Sub-Investigator: Louise Fortes, MD
    • Sub-Investigator: Maguette N. Fall, MD
    • Sub-Investigator: Oumar Kane, MD
    • Sub-Investigator: Papa M. Gueye, Pharmacist
  • Diamniadio, Senegal
    • Not yet recruiting
    • Diamniadio Children Hospital
    • Contact: Aissatou Lakhe, MD; Phone Number: 00221775417301; Email: aissatoulakhe@gmail.com
    • Sub-Investigator: Aissatou Lakhe, MD
    • Sub-Investigator: Pape S. Ba, MD
    • Sub-Investigator: Maguette N. Fall, MD
    • Contact: Maguette N. Fall, MD; Phone Number: 00221777098736; Email: maguifall4@gmail.com
  • Guédiawaye, Senegal
    • Not yet recruiting
    • Dalal Jamm Hospital
    • Sub-Investigator: Aissatou Lakhe, MD
    • Sub-Investigator: Pape S. Ba, MD
    • Sub-Investigator: Louise Fortes, MD
    • Contact: Louise Fortes, MD; Phone Number: 00221775595333; Email: louisefortes@yahoo.fr
    • Contact: Fatou SD Ndiaye, MD; Email: kinepierre1@gmail.com
    • Sub-Investigator: Fatou SD Ndiaye, MD
    • Sub-Investigator: Abdoul Kane, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of Care; 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; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institut Pasteur de Dakar
• Collaborators: Ministry of Health, Senegal; Fann Hospital, Senegal; Diamniadio Children Hospital, Senegal; Dalal Jamm Hospital, Senegal; Institut Pasteur Korea
• Investigators: Principal Investigator: Moussa Seydi, MD, Fann Hospital, Senegal; Study Director: Amadou A. Sall, PhD, Institut Pasteur de Dakar, Senegal; Principal Investigator: Fabien Taieb, MD, PhD, Institut Pasteur de Dakar, Senegal

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2020
• Primary Completion (Anticipated): February 12, 2021
• Study Completion (Anticipated): August 12, 2021

Study Registration Dates

• First Submitted: May 14, 2020
• First Submitted That Met QC Criteria: May 14, 2020
• First Posted (Actual): May 15, 2020

Study Record Updates

• Last Update Posted (Actual): September 7, 2020
• Last Update Submitted That Met QC Criteria: September 3, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Safety; Efficacy; COVID-19; Senegal; Nafamostat mesilate
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Protease Inhibitors; Serine Proteinase Inhibitors; Anticoagulants; Trypsin Inhibitors; Complement Inactivating Agents; Nafamostat
• Other Study ID Numbers: 2020-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No