Clinical trial NCT04356495: Trial of COVID-19 Outpatient Treatment in Individuals With Risk Factors for Aggravation
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Corona Virus Infection
Sars-CoV2
Keywords: Corona virus
Sars-CoV2
telmisartan
ciclesonide
interferon β-1b
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: University of Bordeaux
First posted: 2020-04-22
Enrollment: 412
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pilot Phase: Proportion of participants who had a Grade 3 or 4 adverse event
timeFrame: From inclusion (day0) to day 14
measure: Efficacy phase: Death
timeFrame: From inclusion (day0) to day 14
measure: Efficacy phase: oxygen therapy
timeFrame: From inclusion (day0) to day 14
measure: Efficacy phase: hospitalization
timeFrame: From inclusion (day0) to day 14
Secondary outcomes:
measure: Proportion of hospitalizations, overall and by cause, in each group
timeFrame: From inclusion (day0) to day 28
measure: Death and causes of death
timeFrame: From inclusion (day0) to day 28
measure: Proportion of intensive care hospitalizations, overall and by cause, in each group
timeFrame: From inclusion (day0) to day 28
measure: Proportion of participants with negative SARS-CoV-2 RT-PCR
timeFrame: day 7
measure: Haematological markers evolution
timeFrame: from inclusion (day 0) to day 7
measure: Inflammatory markers evolution
timeFrame: from inclusion (day 0) to day 7
measure: Adverse events
timeFrame: from inclusion (day 0) to day 28
measure: Adverse reactions
timeFrame: from inclusion (day 0) to day 28
measure: Acceptability of the treatment
timeFrame: from inclusion (day 0) to day 10
measure: Antibiotic consumption
timeFrame: from inclusion (day 0) to day 28
measure: Oxygen saturation worsening
timeFrame: from inclusion (day 0) to day 28
measure: protocol follow-up
timeFrame: from inclusion (day 0) to day 10
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Bordeaux university Hospital
city: Dijon
country: France
facility: CHU de Dijon-Bourgogne
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nancy
country: France
facility: CHRU de Nancy
city: Paris
country: France
facility: Groupe hospitalier Paris Saint Joseph
city: Paris
country: France
facility: CNGE
city: Toulouse
country: France
facility: CHU de Toulouse
Study officials:
affiliation: University Hospital, Bordeaux
name: Denis MALVY, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Inserm 1219
name: Xavier ANGLARET, Dr
role: STUDY_DIRECTOR
affiliation: University Hospital, Bordeaux
name: Laura RICHERT, Dr
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.