A randomized trial of efficacy and safety of an early OUTpatient treatment of COVID-19 in patients with risk factor for poor outcome : a strategy to prevent hospitalization: OUTCOV Study

INTERVENTION: Trade Name: PLAQUENIL 200 MG CPR Pharmaceutical Form: Tablet Trade Name: KALETRA 200MG/50MG CPR Pharmaceutical Form: Tablet INN or Proposed INN: LOPINAVIR CAS Number: 192725‐17‐0 Current Sponsor code: LOPINAVIR Other descriptive name: LOPINAVIR Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ INN or Proposed INN: RITONAVIR CAS Number: 155213‐67‐5 Current Sponsor code: RITONAVIR Other descriptive name: RITONAVIR Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ Trade Name: ZITHROMAX 250MG CPR Product Name: AZITHROMYCIN Pharmaceutical Form: Tablet INN or Proposed INN: AZITHROMYCIN CAS Number: 83905‐01‐5 Current Sponsor code: AZITHROMYCIN Other descriptive name: AZITHROMYCIN Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ CONDITION: COVID‐19 patients with risk factor for poor outcome Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: The primary objective of the study is to evaluate the effect of treatment on the reduction of hospitalization rate among COVID19 patients with risk factors of poor prognosis. Primary end point(s): Hospital admission rate between D0 and Day 20 Secondary Objective: To evaluate the effect of treatment on ; 1. Death; 2. Death due to COVID ; 3. Need for ICU stay; 4. Duration of ICU stay; 5. Need of mechanical ventilation; 6. Duration of mechanical ventilation; 7. Time to hospitalization; 8. Duration of Hospital stay; 9. Duration of symptoms; To evaluate the safety of the different arms ; To evaluate the respiratory impairment Timepoint(s) of evaluation of this end point: DAY 20 SECONDARY OUTCOME: Secondary end point(s): 1. Death; 2. Death due to COVID ; 3. Need for ICU stay; 4. Duration of ICU stay; 5. Need of mechanical ventilation; 6. Duration of mechanical ventilation; 7. Time to hospitalization; 8. Duration of Hospital stay; 9. Duration of symptoms; Safety outcome measures between M0 and M6 : ; ; Adverse events/Serious adverse events according to Common Terminology Criteria For Adverse Event (CTCAE)/Discontinuation of experimental treatment ; ; Respiratory impairment at 6 month; Timepoint(s) of evaluation of this end point: 1. Overall survival : D20, D60 (obtain by telephone at D20) ; 2. Mortality link to COVID: D20, D60 (obtain by telephone at D20); 3. Admission in ICU : D20, D60 (obtain by telephone at D20); 4. Duration of ICU stay : D20, D60 (obtain by telephone at D20); 5. Need for mechanical ventilation : D20, D60 (obtain by telephone at D20); 6. Duration of mechanical ventilation : D20, D60 (obtain by telephone at D20); 7. Time to hospitalisation : D20, D60 (obtain by telephone at D20); 8. Duration of hospitalization : D20, D60 (obtain by telephone at D20); 9. Duration of symptoms : D20, D60 (obtain by telephone at D20); Safety outcome measures between M0 and M6; Respiratory impairment at 6 month INCLUSION CRITERIA: 1) Either more than 50 years of age with at least comorbidity (hypertension, diabetes, obesity, cancer, chronic renal disease, immunodeficiency) OR more than 70 years of age with or without comorbidity 2) Laboratory proved infection by COVID‐19 or radiological sign highly suggestive of COVID‐19 3) Respiratory symptoms (cough, chest discomfort, dyspnea) 4) Affiliation to the social security system 5) Able to understand and sign a written informed consent form Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 320 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 320