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

• ClinicalTrials.gov Identifier: NCT04365582
• Recruitment Status: Withdrawn
• First Posted: April 28, 2020
• Last Update Posted: April 27, 2021
• Sponsor: Groupe Hospitalier Paris Saint Joseph
• Information provided by (Responsible Party): Groupe Hospitalier Paris Saint Joseph

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COVID	Drug: Azithromycin; Drug: Hydroxychloroquine; Drug: Lopinavir 200Mg/Ritonavir 50Mg Tab	Phase 3

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 7, 2020
• Actual Primary Completion Date: December 31, 2020
• Actual Study Completion Date: April 19, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Azithromycin; Azithromycin	Drug: Azithromycin; 500 mg day 1 ; 250 mg/day for 4 days
Experimental: Hydroxychlororquine; Hydroxychlororquine	Drug: Hydroxychloroquine; 200 mg x 3/day for 10 days
Experimental: Lopinavir/Ritonavir; Lopinavir/Ritonavir	Drug: Lopinavir 200Mg/Ritonavir 50Mg Tab; 400/100 mg (2 tablets) x 2/day for 15 days; Other Name: Lopinavir/Ritonavir
No Intervention: standards of care; SoC

Outcome Measures

Primary Outcome Measures :

1. Hospital admission [ Time Frame: Day 20 ]
   Hospitalization at D20

Secondary Outcome Measures :

1. Effect of treatment on Death at D20 [ Time Frame: Day 20 ]
   This outcome corresponds to the number of patients who died on day 20.
2. Effect of treatment on Death at D60 [ Time Frame: Day 60 ]
   This outcome corresponds to the number of patients who died on day 60.
3. Effect of treatment on Death due to COVID at D20 [ Time Frame: Day 20 ]
   This outcome corresponds to the number of patients who died due to COVID on day 20.
4. Effect of treatment on Death due to COVID at D60 [ Time Frame: Day 60 ]
   This outcome corresponds to the number of patients who died due to COVID on day 60.
5. Effect of treatment on need for ICU stay at D20 [ Time Frame: Day 20 ]
   This outcome corresponds to the number of participants who need ICU stay at day 20.
6. Effect of treatment on need for ICU stay at D60 [ Time Frame: Day 60 ]
   This outcome corresponds to the number of participants who need ICU stay at day 60.
7. Effect of treatment on duration of ICU stay at D20 [ Time Frame: Day 20 ]
   This outcome evaluates the duration of patient's ICU stay at day 20.
8. Effect of treatment on duration of ICU stay at D60 [ Time Frame: Day 60 ]
   This outcome evaluates the duration of patient's ICU stay at day 60.
9. Effect of treatment on need of mechanical ventilation at D20 [ Time Frame: Day 20 ]
   This outcome corresponds to the number of participants who need mechanical ventilation at D20.
10. Effect of treatment on need of mechanical ventilation at D60 [ Time Frame: Day 60 ]
    This outcome corresponds to the number of participants who need mechanical ventilation at D60.
11. Effect of treatment on duration of mechanical ventilation at D20 [ Time Frame: Day 20 ]
    This outcome corresponds to the duration of patient's mechanical ventilation at D20.
12. Effect of treatment on duration of mechanical ventilation at D60 [ Time Frame: Day 60 ]
    This outcome corresponds to the duration of patient's mechanical ventilation at D60.
13. Effect of treatment on time to hospitalization at D20 [ Time Frame: Day 20 ]
    This outcome evaluates the delay between inclusion and hospitalization at D20.
14. Effect of treatment on time to hospitalization at D60 [ Time Frame: Day 60 ]
    This outcome evaluates the delay between inclusion and hospitalization at D60.
15. Effect of treatment on Duration of Hospital stay et D20 [ Time Frame: Day 20 ]
    This outcome evaluates the duration of patient's Hospital stay at D20.
16. Effect of treatment on Duration of Hospital stay et D60 [ Time Frame: Day 60 ]
    This outcome evaluates the duration of patient's Hospital stay at D60.
17. Effect of treatment on Duration of symptoms at D20 [ Time Frame: Day 20 ]
    This outcome evaluates the duration of symptoms at D20 after treatment.
18. Effect of treatment on Duration of symptoms at D60 [ Time Frame: Day 60 ]
    This outcome evaluates the duration of symptoms at D60 after treatment.
19. Incidence of Treatment-Emergent Adverse Events [ Time Frame: Month 6 ]
    This outcome measures the number of participants with treatment-related adverse events as assessed by CTCAE v4.0, at the end of study.

Other Outcome Measures:

1. Effect of treatment on chest radiological features [ Time Frame: Month 6 ]
   This outcome evaluates the chest radiological features on Chest HRCT, at 6 months, after treatment.
2. Effect of treatment on respiratory capacity [ Time Frame: Month 6 ]
   This outcome evaluates the Pulmonary function test at 6 month, after treatment.
3. Cost consequence analysis [ Time Frame: Month 6 ]
   This ouctome eavaluates costs and consequences which will be presented for each stakeholder in a disaggregated way at the end of study.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. 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
2. Laboratory (PCR-) 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 network
5. Able to understand and sign a written informed consent form

Exclusion Criteria:

1. Need for hospitalization according to updated French guidelines (ministère de la santé_04/04/2020)
2. Patient in long-term care facility
3. Patient without concern confirmation of COVID-19 by laboratory (PCR swab) test or chest CT
4. Known hypersensitivity or contra-indication to the 3 experimental treatments (azithromycin, hydroxychloroquine, lopinavir/ritonavir).
5. Any reason making follow up of the patient impossible during the study period.

Contacts and Locations

Sponsors and Collaborators

Groupe Hospitalier Paris Saint Joseph

Investigators

• Principal Investigator: Jean-Marc Naccache, MD; Groupe Hospitalier Paris Saint Joseph

More Information

Publications:

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• Responsible Party: Groupe Hospitalier Paris Saint Joseph
• ClinicalTrials.gov Identifier: NCT04365582
• Other Study ID Numbers: OUTCOV
• First Posted: April 28, 2020
• Last Update Posted: April 27, 2021
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Groupe Hospitalier Paris Saint Joseph:

COVID; outpatient; ambulatory; prognosis

Additional relevant MeSH terms:

Ritonavir; Lopinavir; Azithromycin; Hydroxychloroquine; HIV Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Anti-Bacterial Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Antirheumatic Agents