EVALUATION OF THE EFFICACY OF THE HYDROXYCHLOROQUINE-AZITHROMYCIN COMBINATION IN THE IN THE PREVENTION OF COVID-19 RELATED SDRA (TEACHCOVID)

Since end of December, a new coronavirus, close to the 2002 SARS coronavirus, cause serious pneumonias throughout world. There is currently no strong evidence of an efficient specific treatment. Hydroxychloroquine is an old chloroquine-derived drug, prescribed for auto-immune disorders. It has shown efficacy against Sars-CoV-2 in vitro. Some studies showed that Hydroxychloroquine might improve the clinical status of Sars-CoV-2 infected patients. Azithromycin is a macrolide antibiotic, with immunomodulatory properties. Adding Azithromycin to a hydroxychloroquine-based treatment showed an apparent accelerated viral clearance in infected patients. This study wants to evaluate the clinical impact of adding Azithromycin to Hydroxychloroquine in the treatment of Sars-CoV-2 pneumonia

Study Overview

• Status: Withdrawn
• Conditions: Sars-CoV-2, Community-Acquired Pneumonia,COVID-19
• Intervention / Treatment: Drug: Hydroxychloroquine; Drug: Control arm; Drug: Hydroxychloroquine and azithromycin treatment arm.

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 18 years old
• Positive Sars-CoV-2 RT-PCR on nasopharyngeal swab
• CT scan suggestive of Sars-CoV-2 pneumonia

Exclusion Criteria:

• Negative Sars-CoV-2 RT-PCR on nasopharyngeal swab
• Known hypersensitivity to Hydroxychloroquine, Azithromycin or a macrolide family member
• Long term prescribed treatment contraindicated with azithromycin (colchicine, ergotamine, dihydroergotamine) and/or hydroxychloroquine (citalopram, escitalopram, hydroxyzine, domperidone, piperaquin)
• Retinopathy or maculopathy
• Porphyria
• Severe renal failure (GFR less than 30 mL/min/m²)
• Dyskaliemia, (ie less than 3,5 mmol/L or more than 5,5 mmol/L)
• Hypomagnesiemia, ie less than 0,7 mmol/L
• Severe cholestasis, cirrhosis or severe hepatic failure
• Known cardiac medical history of congestive heart failure or myocardial infarction
• Bradycardia less than 50 beats per minute
• Prolonged corrected QT interval, (ie cQT more than 440 ms in men and 450 ms in women) or medical history of ventricular cardiac rhythm disorders
• Blood disorders with history of hematopoietic stem cells allograft
• Known history of G6PD deficiency
• Pregnancy
• Breastfeeding
• Subject protected by law under guardianship of curatorship
• Inability to take oral medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydroxychloroquine; Hydroxychloroquine is given for 5 days, with a loading dose of 400 mg qd at D1, and 200 mg qd for the next 4 days (D2-D5). Standard of care is also prescribed (oxygen therapy, analgesics, antipyretics, anticoagulant drug, etc)	Drug: Hydroxychloroquine; Patient allocated in this arm receive hydroxychloroquine for 5 days. For hydroxychloroquine, there is a loading dose of 800 mg per day at D1, followed by 400 mg per day D2-D5. Every patient receives as well antibiotic (ceftriaxone 1-2 g per day IV), and standard of care (oxygen therapy, analgesics, antipyretics, heparin, etc).
Active Comparator: Control; The patient is given antibiotics only. Standard of care is also prescribed (oxygen therapy, analgesics, antipyretics, anticoagulant drug, etc).	Drug: Control arm; In this arm, no experimental treatment is prescribed. Patients receive IV antibiotics and standard of care (oxygen therapy, analgesics, antipyretics, heparin, etc).
Experimental: Hydroxychloroquine and Azithromycin; Hydroxychloroquine is given for 5 days, with a loading dose of 400 mg qd at D1, and 200 mg qd for the next 4 days (D2-D5). Azithromycin is given for 5 days, with a loading dose of 500 mg at D1, and 250 mg for the next 4 days. Standard of care is also prescribed (oxygen therapy, analgesics, antipyretics, anticoagulant drug, etc) In case of moderate renal failure (glomerular filtration rate between 30 and 60 mL/min/m²), hydroxychloroquine dosage are lowered by half.	Drug: Hydroxychloroquine and azithromycin treatment arm.; Patient allocated in this arm receive hydroxychloroquine and azithromycin for 5 days. For hydroxychloroquine, there is a loading dose of 800 mg per day at D1, followed by 400 mg per day D2-D5. For azithromycin, there is a loading dose of 500 mg per day at D1, followed by 250 mg per day D2-D5. Every patient receive as well antibiotic (ceftriaxone 1-2 g per day IV), and standard of care (oxygen therapy, analgesics, antipyretics, heparin, etc).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of patients reaching a significant hypoxemia, in each arms.	A significant hypoxemia is an arterial partial pressure of oxygen of less than 60 mmHg despite an oxygen flow of more than 6 L/min, patient at rest.	From day 0 to day 7

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2020
• Primary Completion (Actual): June 2, 2020
• Study Completion (Actual): June 2, 2020

Study Registration Dates

• First Submitted: April 11, 2020
• First Submitted That Met QC Criteria: April 11, 2020
• First Posted (Actual): April 15, 2020

Study Record Updates

• Last Update Posted (Actual): June 4, 2020
• Last Update Submitted That Met QC Criteria: June 2, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; 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: 7783

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