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

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

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.

Study Overview

• Status: Terminated
• Conditions: Coronavirus Infection; Pneumonia, Viral
• Intervention / Treatment: Drug: Hydroxychloroquine + placebo; Drug: hydroxychloroquine + azithromycin

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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • Montpellier University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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,..

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Jacques REYNES, MD,PhD, Montpellier University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2020
• Primary Completion (Actual): February 9, 2021
• Study Completion (Actual): April 9, 2021

Study Registration Dates

• First Submitted: April 5, 2020
• First Submitted That Met QC Criteria: April 9, 2020
• First Posted (Actual): April 15, 2020

Study Record Updates

• Last Update Posted (Actual): December 15, 2021
• Last Update Submitted That Met QC Criteria: December 14, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; pneumonia; hydroxychloroquine; azithromycin; SARS-CoV2 virus
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; COVID-19; Coronavirus Infections; Pneumonia; Pneumonia, Viral; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Azithromycin; Hydroxychloroquine
• Other Study ID Numbers: RECHMPL20_168

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No