Hydroxychloroquine Plus Azithromycin Versus Hydroxychloroquine for COVID-19 Pneumonia (COVIDOC Trial)

Study Overview
=================
Brief Summary
-----------------
Double blinded randomized clinical trial designed to evaluate the efficacy and safety of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in patients hospitalized with confirmed COVID-19 pneumonia.

Detailed Description
-----------------
The multi-centre COVIDOC study will evaluate the efficacy and safety of the use of hydroxychloroquine (10 days) combined with azithromycin (5 days) compared to hydroxychloroquine (10 days) in the the clinical evolution by the ordinal scale of 7 points in adults hospitalized outside Intensive care unit with pneumonia caused by infection by the SARS-CoV2 virus in France.

Official Title
-----------------
Randomized Trial Assessing Efficacy and Safety of Hydroxychloroquine Plus Azithromycin Versus Hydroxychloroquine for Hospitalized Adults With COVID-19 Pneumonia

Conditions
-----------------
Coronavirus Infection, Pneumonia, Viral

Intervention / Treatment
-----------------
* Drug: Hydroxychloroquine + placebo
* Drug: hydroxychloroquine + azithromycin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18-75 years old SARS CoV-2 Infection confirmed by positive virologic test realised in the 96 h before randomization Beginning of COVID-19 symptoms < 10 days at the time of randomization Presence of symptom(s) of COVID-19 : fever (température > or = 37,5°C) or respiratory sign(s) (cough, breathing discomfort) or recent anosmia Presence of TDM/radiographic signs or pneumonia Hospitalization out of ICU for COVID with: moderate clinical form (no oxygenotherapy) or non critical severe form (oxygenotherapy) Exclusion Criteria: Absence of signed informed consent SpO2 < 90 % ambient air or < 94 % with oxygenotherapy > or = 3l/min Need of oxygenotherapy > 6 l/min or mechanical ventilation Need of hospitalization in ICU ALAT/ASAT > 5 LSN Renal failure (eGFR < 40 ml/min ) or dialysis Pregnancy or breastfeeding Retinopathy Known deficit in G6PD Cardiac rythm / lengthening QT disorders QT space lengthening on ECG with QTc > 450 ms Concomitant treatment :citalopram, escitalopram, hydroxyzine, domperidone, pipéraquine, anti-arhythmic class IA & III, antidepressive drugs,..

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: monotherapy hydroxychloroquine<br>Hydroxychloroquine 800mg (Day 1), 600mg (from Day 2 to Day 10) + placebo from Day 1 to Day 5 | Drug: Hydroxychloroquine + placebo<br>* hydroxychloroquine : 800mg(Day1) then 600 mg (Day 2 to Day 11)<br>|
| Experimental: combination hydroxychloroquine + azithromycin<br>Hydroxychloroquine 800mg (Day 1), 600mg (from Day 2 to Day 10) and azithromycin 500mg (Day 1 ), 250 mg (from day 2 to Day 5) | Drug: hydroxychloroquine + azithromycin<br>* Combination hydroxychloroquine : 800mg(Day1) then 600 mg (Day 2 to Day 11) Azithromycin 500mg (day 1) then 250 mg (Day 2 to Day 5)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical improvement of at least 1 level on the ordinal scale between Day 1 (day of the first administration of study drug) to Day 11 (day after last day of treatment). | Evaluation of the clinical status of patient defined by the Ordinal Scale of 7 points (score range from 1 to 7 , with 7 being the worst score) | up to Day 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical status assessed by ordinal scale | Evaluation of the clinical status of patient defined by the Ordinal Scale of 7 points at day 15 and day 29 | up to Day 29 | 
| transfer to ICU | Necessity for transfer to Intensive care unit | up to Day 29 | 
| Length of hospital day | days from admission to hospital discharge | up to Day 29 | 
| Hospital Mortality | incidence of all-cause mortality | Day 29 | 
| Need to Mechanical Ventilation | Need to mechanical ventilation | up to Day 29 | 
| Occurence of grade 3-4 adverse event | adverse reactions | up to Day 29 | 
| QTc Lengthening | ECG | up to Day 11 | 
| Evolution of pulmonary CT scan images | Thoracic CT scan : number and size of ground-glass opacifications on day 1 and day 11 Two independent pulmonary imagery experts will assess abnormalities according to a standardized framework | up to Day 11 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SARS-CoV2 virus, COVID-19, pneumonia, hydroxychloroquine, azithromycin