Trial of COVID-19 Outpatient Treatment in Individuals With Risk Factors for Aggravation (COVERAGEFrance)

Randomized Trial to Evaluate the Safety and Efficacy of Outpatient Treatments to Reduce the Risk of Worsening in Individuals With COVID-19 With Risk Factors (COVERAGE France)

In adults with COVID-19 without criteria for hospitalization or oxygen therapy but with risk factors for aggravation, early treatment may avoid hospitalization, indication for oxygen therapy or death. No treatment is currently validated for this indication.

Study Overview

• Status: Completed
• Conditions: Corona Virus Infection; Sars-CoV2
• Intervention / Treatment: Dietary supplement: Vitamins; Drug: Telmisartan; Drug: Ciclesonide; Drug: interferon β-1b

Detailed Description

COVERAGE France is Multicenter, randomized, controlled clinical trial with for each drug :

• A safety study pilot phase.
• An efficacy study phase. The data collected during the pilot phase, combined with new external data that emerged during the period, will be used to position treatments for the efficacy phase.
• Pilot phase will evaluate the tolerance of experimental treatments for drugs given for the first time ("first in home-based care") in ambulatory individuals with COVID-19 with aggravating risk factors.
• Efficacy Phase: To estimate the effectiveness of experimental ambulatory treatments, compared to vitamin supplementation, in reducing the risk of hospitalization, oxygen therapy indication or death in ambulatory individuals with COVID-19 with aggravating risk factors.

The trial is a national platform with the vocation to open as many centers as possible, subject to criteria set by the Scientific Advisory Board.

• Study Type: Interventional
• Enrollment (Actual): 412
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33000
    • Bordeaux University Hospital
  • Dijon, France
    • CHU de Dijon-Bourgogne
  • Montpellier, France, 34295
    • CHU de Montpellier
  • Nancy, France
    • CHRU de NANCY
  • Paris, France, 75014
    • Groupe Hospitalier Paris Saint Joseph
  • Paris, France
    • CNGE
  • Toulouse, France
    • CHU de Toulouse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Clinical picture suggestive of COVID-19 dated 7 days or less.
• Positivity of a test proving an acute SARS-CoV-2 infection, according to current recommendations.
• Absence of criteria for hospitalization or oxygen therapy according to current recommendations.

• Age :

  • greater than or equal to 60 years of age without any risk factor

  • or between 50 and 59 years of age and the presence of at least one of the following risk factors :

    • Arterial hypertension under treatment (all stages)
    • Obesity (BMI ≥30 kg/m2)
    • Diabetes under treatment (all types)
    • Ischemic heart disease (all stages)
    • Heart failure (all stages)
    • Stroke History
    • Chronic Obstructive Pulmonary Disease (all stages)
    • Stage 3 chronic renal failure (30 ≤ Estimated GFR < 60 mL/min/1.73 m²)
    • Malignancies (solid tumours or blood malignancies) that are progressive or were diagnosed less than 5 years ago.
    • Immunodeficiency
• of therapeutic origin (solid organ transplant or hematopoietic stem cell transplant, cancer chemotherapy, immunosuppressive therapy, corticosteroids > 15 mg/d of prednisone equivalent taken for at least 2 months);
• HIV infection with CD4<200/mm3.
• Valid, ambulatory person, fully able to understand the issues of the trial
• Beneficiary of a Social Security scheme
• Signed informed consent

Exclusion Criteria:

• Asymptomatic person
• Inability to make a decision to participate (dementia, person under legal protection, curatorship or guardianship)
• Ongoing illness or chronic treatment contraindicated by taking one of the trial drugs.

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
Sham Comparator: Vitamins; Patients in this arm will receive a vitamin supplement ("AZINC forme et vitalité®") during 10 days	Dietary supplement: Vitamins; 2 tablets daily from the first day (day 0) to day 9
Experimental: Telmisartan; Patients in this arm will receive Telmisartan (Micardis® 20 mg) during 10 days	Drug: Telmisartan; 1 tablet daily from the first day (day 0) to day 9
Experimental: Ciclesonide; Patients in this arm will receive ciclesonide (Alvesco® 160 µg ) during 10 days	Drug: Ciclesonide; 2 puffs twice a day in an inhalation chamber from the first day (day 0) to day 9
Experimental: interferon β-1b; Patients in this arm will receive interferon β-1b (Extavia® 9,6 MUI/300 µg ) during 5 days	Drug: interferon β-1b; A 10-minute nebulization, once a day, from the first day (day 0) to day 4, of 9.6 MIU / 300 µg of IFN-β-1b (EXTAVIA®) diluted in 2 mL of water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pilot Phase: Proportion of participants who had a Grade 3 or 4 adverse event		From inclusion (day0) to day 14
Efficacy phase: Death	Proportion of participants with an occurrence of death	From inclusion (day0) to day 14
Efficacy phase: oxygen therapy	Proportion of participants who had an indication for oxygen therapy	From inclusion (day0) to day 14
Efficacy phase: hospitalization	Proportion of participants who had an indication for hospitalization	From inclusion (day0) to day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of hospitalizations, overall and by cause, in each group		From inclusion (day0) to day 28
Death and causes of death	Proportion of deaths, overall and by cause, in each group	From inclusion (day0) to day 28
Proportion of intensive care hospitalizations, overall and by cause, in each group		From inclusion (day0) to day 28
Proportion of participants with negative SARS-CoV-2 RT-PCR		day 7
Haematological markers evolution	Evolution of Haematological markers in each group : Complete Blood Count, prothrombin level, INR	from inclusion (day 0) to day 7
Inflammatory markers evolution	Evolution of Inflammatory markers in each group : PCT, CRP	from inclusion (day 0) to day 7
Adverse events	Number and proportion of grade 1,2,3,4 adverse events in each group	from inclusion (day 0) to day 28
Adverse reactions	Number and proportion of grade 1,2,3,4 adverse events in each group	from inclusion (day 0) to day 28
Acceptability of the treatment	Acceptability of the treatment by participant will be assessed with an interview	from inclusion (day 0) to day 10
Antibiotic consumption	Proportion of participants who received at least one day of antibiotic therapy	from inclusion (day 0) to day 28
Oxygen saturation worsening	Proportion of participants who experienced a worsening of oxygen saturation	from inclusion (day 0) to day 28
protocol follow-up	Proportion of participants who completed the prescribed protocol treatment	from inclusion (day 0) to day 10

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Collaborators: University of Bordeaux
• Investigators: Principal Investigator: Denis MALVY, Pr, University Hospital, Bordeaux; Study Director: Xavier ANGLARET, Dr, Inserm 1219; Study Chair: Laura RICHERT, Dr, University Hospital, Bordeaux

Publications and helpful links

General Publications

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
• Duvignaud A, Lhomme E, Pistone T, Onaisi R, Sitta R, Journot V, Nguyen D, Peiffer-Smadja N, Cremer A, Bouchet S, Darnaud T, Poitrenaud D, Piroth L, Binquet C, Michel JF, Lefevre B, Lebeaux D, Lebel J, Dupouy J, Roussillon C, Gimbert A, Wittkop L, Thiebaut R, Orne-Gliemann J, Joseph JP, Richert L, Anglaret X, Malvy D; COVERAGE study group. Home Treatment of Older People with Symptomatic SARS-CoV-2 Infection (COVID-19): A structured Summary of a Study Protocol for a Multi-Arm Multi-Stage (MAMS) Randomized Trial to Evaluate the Efficacy and Tolerability of Several Experimental Treatments to Reduce the Risk of Hospitalisation or Death in outpatients aged 65 years or older (COVERAGE trial). Trials. 2020 Oct 13;21(1):846. doi: 10.1186/s13063-020-04619-1.
• Garcia G, Labrouche-Colomer S, Duvignaud A, Clequin E, Dussiau C, Tregouet DA, Malvy D, Prevel R, Zouine A, Pellegrin I, Goret J, Mamani-Matsuda M, Dewitte A, James C. Impaired balance between neutrophil extracellular trap formation and degradation by DNases in COVID-19 disease. J Transl Med. 2024 Mar 7;22(1):246. doi: 10.1186/s12967-024-05044-7.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2020
• Primary Completion (Actual): October 8, 2021
• Study Completion (Actual): October 22, 2021

Study Registration Dates

• First Submitted: April 11, 2020
• First Submitted That Met QC Criteria: April 19, 2020
• First Posted (Actual): April 22, 2020

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Sars-CoV2; telmisartan; ciclesonide; Corona virus; interferon β-1b
• Additional Relevant MeSH Terms: Infections; RNA Virus Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; Coronavirus Infections; Physiological Effects of Drugs; Micronutrients; Organic Chemicals; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmacologic Actions; Chemical Actions and Uses; Hydrocarbons; Hydrocarbons, Cyclic; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Hydrocarbons, Aromatic; Benzene Derivatives; Biphenyl Compounds; Nutrients; Telmisartan; Vitamins; ciclesonide
• Other Study ID Numbers: CHUBX 2020/12; 2020-001435-27 (EudraCT Number)

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