Clinical trial NCT04390594: Efficacy and Safety Evaluation of Treatment Regimens in Adult COVID-19 Patients in Senegal
Official title: Multicentre, Open Label, Randomised, Adaptative Clinical Trial of Efficacy and Safety of Treatment Regimens in Adult COVID-19 Patients in Senegal
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: COVID-19
Keywords: COVID-19
SARS-CoV-2
Efficacy
Safety
Senegal
Nafamostat mesilate
Lead sponsor: Institut Pasteur de Dakar
Sponsor class: OTHER
Collaborators: name: Fann Hospital, Senegal
name: Ministry of Health, Senegal
name: Diamniadio Children Hospital, Senegal
name: Dalal Jamm Hospital, Senegal
name: Institut Pasteur Korea
First posted: 2020-05-15
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: SARS-CoV-2 viral load level
timeFrame: Day 7
Secondary outcomes:
measure: Vital status
timeFrame: Day 15
measure: Proportion of patients with serious adverse events reported during the clinical trial.
timeFrame: through study completion, an average of 7 months
measure: Length of hospitalization
timeFrame: through hospitalization, an average of 2 weeks
measure: Length of hospitalization in a resuscitation unit
timeFrame: through hospitalization, an average of 2 weeks
measure: Duration of oxygen therapy
timeFrame: through hospitalization, an average of 2 weeks
measure: Maximum quick SOFA (qSOFA) score during hospitalisation
timeFrame: through hospitalization, an average of 2 weeks
measure: Clinical status on the seven-category ordinal scale
timeFrame: through hospitalization, an average of 2 weeks
Other outcomes:
Locations:
city: Dakar
country: Senegal
facility: Infectious and Tropical Diseases Department, Fann Hospital
city: Diamniadio
country: Senegal
facility: Diamniadio Children Hospital
city: Guédiawaye
country: Senegal
facility: Dalal Jamm Hospital
Study officials:
affiliation: Fann Hospital, Senegal
name: Moussa Seydi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Pasteur de Dakar, Senegal
name: Amadou A. Sall, PhD
role: STUDY_DIRECTOR
affiliation: Institut Pasteur de Dakar, Senegal
name: Fabien Taieb, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: