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

NCT04347512 | Withdrawn Phase 3

• 1 other identifier: 7783
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

Hydroxychloroquine

EXPERIMENTAL

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

Control

ACTIVE COMPARATOR

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

Drug: Control arm

Hydroxychloroquine and Azithromycin

EXPERIMENTAL

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.

Interventions

Hydroxychloroquine and azithromycin treatment arm. 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).

Hydroxychloroquine and Azithromycin

Hydroxychloroquine 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).

Hydroxychloroquine

Control arm DRUG

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

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

MeSH Terms

Conditions

Community-Acquired Pneumonia; COVID-19

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2020
• First Posted: April 15, 2020
• Study Start: June 2, 2020
• Primary Completion: June 2, 2020
• Study Completion: June 2, 2020
• Last Updated: June 4, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share