Early Treatment of Vulnerable Individuals With Non-Severe SARS-CoV-2 Infection (COVERAGE-A)

Early Treatment of Vulnerable Individuals With Non-Severe SARS-CoV-2 Infection: A Multi-Arm Multi-Stage Randomized Trial (MAMS) to Evaluate the Effectiveness of Several Specific Treatments in Reducing the Risk of Clinical Worsening or Death in Sub-Saharan Africa (COVERAGE-Africa)

Coverage Africa is a nested study in the large Anticov platform trial that aims to generate data on new early treatment strategies for mild/moderate COVID-19 patients in resource-limited-settings to reduce the number progressing to severe forms requiring hospitalization, thereby relieving the burden on health care systems and contributing to "flattening the curve" in contexts where none pharmaceutical intervention such as quarantine are difficult to implement in large urban settings. Treating early when the virus is still present might also limit transmission. Coverage Africa will be conducted in Guinea and Burkina Faso.

The main objective is to conduct an open-label, multicenter, randomized, adaptive platform trial to test the safety and efficacy of several marketed products, including antiviral therapies versus control in mild/moderate of coronavirus disease 2019 (Covid-19) in resource-limited-settings.

The study aims to recruit 600 patients in both countries, one site in Guinea and two sites in Burkina Faso.

The current assessed treatments are now the association of Fluoxétine/Budésonide compared with a control arm: paracetamol.

The adaptive design trial will allow for the removal of drugs, or the addition of new study arms when new data becomes available. Data on the primary efficacy parameters and safety will be integrated with the primary endpoint based on an oxygen saturation percentage (SpO2) ≤ 93% or death within 14 days after randomization to treatment, including death for any reason.

Study will run until August 2022. However, with the proposed adaptive design, the study could also be interrupted for success earlier than planned with the identification of a treatment that significantly reduces hospitalization rate as evidence by results from the primary endpoint.

Study Overview

• Status: Recruiting
• Conditions: Covid19; SARS-CoV2 Infection; Severe Acute Respiratory Syndrome Coronavirus 2; Covid19 Drug Treatment
• Intervention / Treatment: Drug: Paracetamol; Drug: Nitazoxanide and Ciclésonide; Drug: Telmisartan 20Mg Oral Tablet; Drug: Fluoxétine and Budésonide

• Study Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Olivier Marcy, Dr; Phone Number: +33 557 57 47 23; Email: olivier.marcy@u-bordeaux.fr
• Study Contact Backup: Name: Anthony L'Hostellier; Phone Number: +33 557 57 47 23; Email: anthony.lhostellier@u-bordeaux.fr

Study Locations

• Burkina Faso
  • Bobo-Dioulasso, Burkina Faso
    • Recruiting
    • Centre Muraz/INSP
    • Contact: Armel Poda, Pr.; Phone Number: +226 65314949; Email: armelpoda@yahoo.fr
    • Contact: Apoline Sondo, Pr; Phone Number: +226 70077198; Email: sondoapoline@yahoo.fr
• Guinea
  • Conakry, Guinea
    • Suspended
    • Centre de traitement des maladies à tendance épidémique de Gbessia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults 18 years of age at the time of screening or >= 40 years and presenting at least one comorbidity : high blood pressure; a known obesity and/ or a known and treated diabete.
• SARS-CoV-2 infection confirmed by molecular biology (RT-PCR on a nasopharyngeal or oropharyngeal swab) or by antigen test validated in the country according to national guidelines
• A viral syndrome with or without uncomplicated pneumonia, defined as blood oxygen saturation level (SpO2) >=94%.
• Mild Covid-19 symptoms with an onset < 7 days before inclusion.
• Signed written consent from the patient or his/her representative.
• No need an oxygen therapy according to international guidelines (WHO Progression Scale, grade 2 to 4)
• Accepting and having the ability to be reached by telephone throughout the study.
• Having designated a contact person who can be contacted in case of emergency.
• Accepted to be reached by phone along throughout the study

Exclusion Criteria:

• Blood oxygen saturation level (SpO2) < 94%.
• Known hypersensitivity to investigational products
• Chronic treatment with inhaled corticosteroids (up to 30 days)
• Known history of renal or hepatic failure

• Abnormal physical examination findings:

  • respiratory rate < 25 per minute;
  • Clinical hypotension with associated signs justifying hospital care
• Feeling unwell for more than 7 days prior to screening.
• End-organ compromise requiring admission to a resuscitation or continuous care unit or short-term life-threatening comorbidity with life expectancy < 3 months.
• For any new antiviral included in the study, prior treatment with the antiviral, presence of contraindication to its use or intake of concomitant medication proscribed with its use.
• Patients with known suicidal thoughts, severe psychiatric disorders or major depression that is uncontrolled or controlled by one of the prohibited drugs
• Known history of long QT syndrome or severe ventricular cardiac arrhythmia (ventricular tachycardia, patients with recovered ventricular fibrillation)
• Unwilling or unable to comply with the requirements of the study protocol at any time during the study, e.g. no access to or not comfortable with use of a smartphone or with answering questions using a telephone, in the opinion of the Investigator or cannot use an inhalation chamber.
• Any other reason that makes it impossible to monitor the patient during the study.
• Enrolled in other clinical trials with unregistered drugs or with registered drugs that may interact with any of the study IPs or are contraindicated as concomitant therapy within the last 3 months prior to screening

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Paracetamol; Patients in this arm will receive paracetamol during 14 days	Drug: Paracetamol; Tablets containing 500 mg of paracetamol. One to two tablets every 4-6 hours as required, to a maximum of 6 tablets (3 grams) daily in divided doses. Duration of treatment: up to 14 days
Experimental: Nitazoxanide and Ciclésonide; Patients in this arm will receive the combination of ciclezonide (Alvesco® 160 µg ) / nitazoxanide (Netazox® 500 mg) during 14 days	Drug: Nitazoxanide and Ciclésonide; Inhaled Ciclésonide: 320 mcg BID per day and Oral Nitazoxanide:2000 mg tablets daily (divided into two daily intakes of two tablets of nitazoxanide 500 mg) during 14 days.
Experimental: Telmisartan; Patients in this arm will receive telmisartan (Micardis® 20 mg) during 10 days	Drug: Telmisartan 20Mg Oral Tablet; 20 mg tablet daily
Experimental: Fluoxétine and Budésonide; Patients in this arm will receive the combination of Fluoxétine (Fluoxétine Arrow® 40 mg ) / Budésonide (Budecort® 2*400 mcg) during 7 days	Drug: Fluoxétine and Budésonide; Inhaled Budésonide: 400mcg BID per day and oral Fluoxétine : 80mg tablets daily (divided into two daily intakes of two tablets of Fluoxétine 40 mg) during 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SpO2 ≤ 93% within 14 days	Percentage of participant presenting an oxygen saturation percentage (SpO2) ≤ 93% or death within 14 days after randomization to treatment.	From inclusion (day 0) to day 14.
Death within 14 days	Percentage of participant dead within 14 days after randomization to treatment, including death for any reason.	From inclusion (day 0) to day 14.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death within 28 days	Percentage of participant dead within 28 days after randomization to treatment, including death for any reason.	From inclusion (day 0) to day 28.
Occurence of at least one grade 3 or 4 clinical or biological adverse event within 14 days	Occurence of at least one grade 3 or 4 clinical or biological adverse event within 14 days	From inclusion (day 0) to day 14.
Number of hospitalizations due to severe progression	Hospitalisation due to aggravation of COVID-19, including hospitalisation's reason as described below; Request of mechanical ventilation and/or Intensive Care Unit (ICU); Non-ICU hospitalisation, requiring supplemental oxygen; Non-ICU hospitalisation, not requiring supplemental oxygen	From inclusion (day 0) to day 28.

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; University of Bordeaux; Barcelona Institute for Global Health; Centre Muraz; Alliance for International Medical Action; PACCI Program

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2021
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: May 4, 2021
• First Submitted That Met QC Criteria: June 8, 2021
• First Posted (Actual): June 10, 2021

Study Record Updates

• Last Update Posted (Actual): January 31, 2023
• Last Update Submitted That Met QC Criteria: January 30, 2023
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Severe Acute Respiratory Syndrome; COVID-19; Infections; Communicable Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antipyretics; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antiparasitic Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Anti-Allergic Agents; Budesonide; Acetaminophen; Ciclesonide; Fluoxetine; Telmisartan; Nitazoxanide
• Other Study ID Numbers: ANRS COV33 COVERAGE-Africa

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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