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

COVID-19 Clinical Trial

— SEN-CoV-Fadj  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04390594
• Other study ID #: 2020-002
• Status: Recruiting
• Phase: Phase 3
• Start date: August 13, 2020
• Est. completion date: August 12, 2021

Study information

• Verified date: September 2020
• Source: Institut Pasteur de Dakar
• Contact: Fabien Taieb, MD, PhD
• Phone: 00221770979235
• Email: Fabien.taieb[@]pasteur.sn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 186
• Est. completion date: August 12, 2021
• Est. primary completion date: February 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19

Intervention

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

Locations

Country	Name	City	State
Senegal	Infectious and Tropical Diseases Department, Fann Hospital	Dakar
Senegal	Diamniadio Children Hospital	Diamniadio
Senegal	Dalal Jamm Hospital	Guédiawaye

Sponsors (6)

Lead Sponsor	Collaborator
Institut Pasteur de Dakar	Dalal Jamm Hospital, Senegal, Diamniadio Children Hospital, Senegal, Fann Hospital, Senegal, Institut Pasteur Korea, Ministry of Health, Senegal

Country where clinical trial is conducted

Senegal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SARS-CoV-2 viral load level	Real time-PCR (RT-PCR) result of the naso- and oro-pharyngeal sample	Day 7
Secondary	Vital status		Day 15
Secondary	Proportion of patients with serious adverse events reported during the clinical trial.		through study completion, an average of 7 months
Secondary	Length of hospitalization		through hospitalization, an average of 2 weeks
Secondary	Length of hospitalization in a resuscitation unit		through hospitalization, an average of 2 weeks
Secondary	Duration of oxygen therapy		through hospitalization, an average of 2 weeks
Secondary	Maximum quick SOFA (qSOFA) score during hospitalisation		through hospitalization, an average of 2 weeks
Secondary	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