OUTpatient Treatment of COVID-19 in Patients With Risk Factor for Poor Outcome

Study Overview
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Brief Summary
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COVID-19 is a respiratory disease due to a novel coronavirus (SARS-CoV-2) that causes substantial morbidity and mortality. To date, no treatment has been proved to be effective in COVID-19. Elderly patients and patients with comorbidities have the worse prognosis with a higher risk of hospitalization, ICU admission and death. The efficacy of an early outpatient treatment could be suggested but need to be confirmed. This confirmation is mandatory to improve prognosis of COVID-19 but also to avoid unsuspected deleterious effect of drugs already used in clinical practice but not based on evidence.

Detailed Description
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The investigators make the hypothesis that an early outpatient treatment of COVID among patient with respiratory symptoms and risk factors for poor outcome can improve the prognosis of these patient and decrease the need for hospital admission. Our study is an open label randomized clinical trial comparing 4 arms of treatment: Standards of Care (SoC) alone versus SoC + Azithromycine versus SoC + Hydroxychloroquine vs Soc + Lopinavir/Ritonavir. Our involved population is patients more than 50 years of age with comorbidity or patients more than 70 years of age. Our primary objective is to evaluate the efficacy of early outpatient treatment compared to standard of care in patients COVID-19 with risk factors for poor outcome. The criteria is hospital admission at Day 20 and the hospital admission rate will be compared between groups by a Chi² test or a Fisher's exact test.

Official Title
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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

Conditions
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COVID

Intervention / Treatment
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* Drug: Azithromycin
* Drug: Hydroxychloroquine
* Drug: Lopinavir 200Mg/Ritonavir 50Mg Tab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Either patients over 50 years of age with at least one comorbidity (hypertension, diabetes, obesity, cancer, chronic renal disease, immunodeficiency) OR patients over 70 years of age with or without comorbidity Laboratory (PCR-) proved infection by COVID-19 or radiological sign highly suggestive of COVID-19 Respiratory symptoms (cough, chest discomfort, dyspnea) Affiliation to the social security network Able to understand and sign a written informed consent form Exclusion Criteria: Need for hospitalization according to updated French guidelines (ministère de la santé_04/04/2020) Patient in long-term care facility Patient without concern confirmation of COVID-19 by laboratory (PCR swab) test or chest CT Known hypersensitivity or contra-indication to the 3 experimental treatments (azithromycin, hydroxychloroquine, lopinavir/ritonavir). Any reason making follow up of the patient impossible during the study period.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azithromycin<br>Azithromycin | Drug: Azithromycin<br>* 500 mg day 1 ; 250 mg/day for 4 days<br>|
| Experimental: Hydroxychlororquine<br>Hydroxychlororquine | Drug: Hydroxychloroquine<br>* 200 mg x 3/day for 10 days<br>|
| Experimental: Lopinavir/Ritonavir<br>Lopinavir/Ritonavir | Drug: Lopinavir 200Mg/Ritonavir 50Mg Tab<br>* 400/100 mg (2 tablets) x 2/day for 15 days<br>* Other names: Lopinavir/Ritonavir;|
| No Intervention: standards of care<br>SoC | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital admission | Hospitalization at D20 | Day 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of treatment on Death at D20 | This outcome corresponds to the number of patients who died on day 20. | Day 20 | 
| Effect of treatment on Death at D60 | This outcome corresponds to the number of patients who died on day 60. | Day 60 | 
| Effect of treatment on Death due to COVID at D20 | This outcome corresponds to the number of patients who died due to COVID on day 20. | Day 20 | 
| Effect of treatment on Death due to COVID at D60 | This outcome corresponds to the number of patients who died due to COVID on day 60. | Day 60 | 
| Effect of treatment on need for ICU stay at D20 | This outcome corresponds to the number of participants who need ICU stay at day 20. | Day 20 | 
| Effect of treatment on need for ICU stay at D60 | This outcome corresponds to the number of participants who need ICU stay at day 60. | Day 60 | 
| Effect of treatment on duration of ICU stay at D20 | This outcome evaluates the duration of patient's ICU stay at day 20. | Day 20 | 
| Effect of treatment on duration of ICU stay at D60 | This outcome evaluates the duration of patient's ICU stay at day 60. | Day 60 | 
| Effect of treatment on need of mechanical ventilation at D20 | This outcome corresponds to the number of participants who need mechanical ventilation at D20. | Day 20 | 
| Effect of treatment on need of mechanical ventilation at D60 | This outcome corresponds to the number of participants who need mechanical ventilation at D60. | Day 60 | 
| Effect of treatment on duration of mechanical ventilation at D20 | This outcome corresponds to the duration of patient's mechanical ventilation at D20. | Day 20 | 
| Effect of treatment on duration of mechanical ventilation at D60 | This outcome corresponds to the duration of patient's mechanical ventilation at D60. | Day 60 | 
| Effect of treatment on time to hospitalization at D20 | This outcome evaluates the delay between inclusion and hospitalization at D20. | Day 20 | 
| Effect of treatment on time to hospitalization at D60 | This outcome evaluates the delay between inclusion and hospitalization at D60. | Day 60 | 
| Effect of treatment on Duration of Hospital stay et D20 | This outcome evaluates the duration of patient's Hospital stay at D20. | Day 20 | 
| Effect of treatment on Duration of Hospital stay et D60 | This outcome evaluates the duration of patient's Hospital stay at D60. | Day 60 | 
| Effect of treatment on Duration of symptoms at D20 | This outcome evaluates the duration of symptoms at D20 after treatment. | Day 20 | 
| Effect of treatment on Duration of symptoms at D60 | This outcome evaluates the duration of symptoms at D60 after treatment. | Day 60 | 
| Incidence of Treatment-Emergent Adverse Events | This outcome measures the number of participants with treatment-related adverse events as assessed by CTCAE v4.0, at the end of study. | Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID, outpatient, ambulatory, prognosis