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

NCT ID: NCT04347512

Last Updated: 2020-06-04

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-02
• Study Completion Date: 2020-06-02

Brief Summary

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

Conditions

Sars-CoV-2, Community-Acquired Pneumonia,COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Hydroxychloroquine

Intervention Type: DRUG

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).

Control

The patient is given antibiotics only. Standard of care is also prescribed (oxygen therapy, analgesics, antipyretics, anticoagulant drug, etc).

Group Type: ACTIVE_COMPARATOR

Control arm

Intervention Type: DRUG

In this arm, no experimental treatment is prescribed. Patients receive IV antibiotics and standard of care (oxygen therapy, analgesics, antipyretics, heparin, etc).

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.

Group Type: EXPERIMENTAL

Hydroxychloroquine and azithromycin treatment arm.

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: 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).

Intervention Type: 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).

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Strasbourg, France

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

7783

Identifier Type: -

Identifier Source: org_study_id