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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Sars-CoV2, Corona Virus Infection

Intervention / Treatment
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* Dietary Supplement: Vitamins
* Drug: Telmisartan
* Drug: Ciclesonide
* Drug: interferon β-1b


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Vitamins<br>Patients in this arm will receive a vitamin supplement (AZINC forme et vitalité®) during 10 days | Dietary Supplement: Vitamins<br>* 2 tablets daily from the first day (day 0) to day 9<br>|
| Experimental: Telmisartan<br>Patients in this arm will receive Telmisartan (Micardis® 20 mg) during 10 days | Drug: Telmisartan<br>* 1 tablet daily from the first day (day 0) to day 9<br>|
| Experimental: Ciclesonide<br>Patients in this arm will receive ciclesonide (Alvesco® 160 µg ) during 10 days | Drug: Ciclesonide<br>* 2 puffs twice a day in an inhalation chamber from the first day (day 0) to day 9<br>|
| Experimental: interferon β-1b<br>Patients in this arm will receive interferon β-1b (Extavia® 9,6 MUI/300 µg ) during 5 days | Drug: interferon β-1b<br>* 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<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Corona virus, Sars-CoV2, telmisartan, ciclesonide, interferon β-1b