Hydroxychloroquine Versus Placebo in COVID-19 Patients at Risk for Severe Disease

NCT ID: NCT04325893

Last Updated: 2020-10-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 259 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-01
• Study Completion Date: 2020-06-18

Brief Summary

A new human coronavirus responsible for pneumonia, SARS-CoV-2, emerged in China in December 2019 and has spread rapidly. COVID-19, the disease caused by this virus, has a very polymorphous clinical presentation, which ranges from upper respiratory tract infections to acute respiratory distress syndrome. It may appear serious straightaway or may evolve in two stages, with a worsening 7 to 10 days after the first clinical signs, potentially linked to a cytokine storm and accompanied by a high risk of thrombosis. The global mortality rate of COVID-19 is between 3% and 4%, with severe forms being more frequent among older patients. Management is symptomatic as no antiviral treatment has demonstrated any clinical benefit in this condition. Hydroxychloroquine is a derivative of chloroquine commonly used in some autoimmune diseases, such as systemic lupus erythematosus. It is active in vitro in cellular models of infection by many viruses such as HIV, hepatitis C or SARS-CoV. However, its interest in viral infections in humans has not been demonstrated.

Very recently, a preliminary uncontrolled study evaluated the effect of hydroxychloroquine on viral shedding in subjects with COVID-19. Among 20 patients treated with hydroxychloroquine at a dose of 600 mg per day, the percentage of patients with detectable SARS-CoV-2 RNA in the nasopharynx decreased from 100% at inclusion (start of treatment) to 43% six days later. In comparison, 15 of 16 untreated patients had a positive RT-PCR six days after inclusion. Furthermore, hydroxychloroquine has immunomodulating and anti-inflammatory properties, which could theoretically prevent or limit secondary worsening.

The research hypothesis is that treatment with hydroxychloroquine improves prognosis and reduces the risk of death or use for invasive ventilation in patients with COVID-19.

Conditions

Coronavirus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Hydroxychloroquine

Group Type: ACTIVE_COMPARATOR

Hydroxychloroquine

Intervention Type: DRUG

First dose of 400 mg will be taken immediately after inclusion at day 0, the second dose of 400 mg will be taken on the same evening and at least 4 hours after the first dose. The treatment will then be continued for the following eight days at a rate of 200 mg in the morning and evening.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

TFirst dose of 400 mg will be taken immediately after inclusion at day 0, the second dose of 400 mg will be taken on the same evening and at least 4 hours after the first dose. The treatment will then be continued for the following eight days at a rate of 200 mg in the morning and evening.

Interventions

Hydroxychloroquine

First dose of 400 mg will be taken immediately after inclusion at day 0, the second dose of 400 mg will be taken on the same evening and at least 4 hours after the first dose. The treatment will then be continued for the following eight days at a rate of 200 mg in the morning and evening.

Intervention Type: DRUG

Placebo

TFirst dose of 400 mg will be taken immediately after inclusion at day 0, the second dose of 400 mg will be taken on the same evening and at least 4 hours after the first dose. The treatment will then be continued for the following eight days at a rate of 200 mg in the morning and evening.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years old
• Symptomatic infection with COVID-19 confirmed by positive RT-PCR SARS-CoV-2 or, failing that, by thorax CT-scan suggesting viral pneumopathy of peripheral predominance in a clinically significant context.
• Diagnosis in the previous two calendar days or, for an asymptomatic patient at the time of virological diagnosis, onset of symptoms in the previous two calendar days.
• Patient having at least one of the following risk factors for developing complications:

• Age ≥75 years old
• Age between 60 and 74 years old and presence of at least one comorbidity among the following: obesity (body mass index ≥ 30 kg/m²), arterial hypertension requiring treatment, diabetes mellitus requiring treatment
• Need for supplemental oxygen to reach a peripheral capillary oxygen saturation of more than 94% (SpO2 > 94%), or a ratio of partial oxygen pressure to the fraction of inspired oxygen less than or equal to 300 mmHg (PaO2/FiO2 ≤ 300 mmHg).
• Patient affiliated to a social security scheme.
• Written and signed consent of the patient or a relative or emergency inclusion procedure.

Exclusion Criteria

• Last RT-PCR negative for SARS-CoV-2
• Peripheral capillary oxygen saturation less than or equal to 94% (SpO2 ≤ 94%) despite oxygen therapy greater than or equal to 3 L/min (> 3 L/min)
• Organ failure requiring admission to a critical or intensive care unit.
• Comorbidity that is life threatening in the short-term (life expectancy < 3 months)
• Any reason that makes patient follow-up throughout the study impossible
• Current treatment with hydroxychloroquine
• Absolute contraindication to treatment with hydroxychloroquine (known hypersensitivity, retinopathy, concomitant treatment with risk of ventricular disorders, particularly torsades de pointe, known deficit of glucose-6-phosphate dehydrogenase, porphyria)
• Hypokalaemia < 3.5 mmol/L
• Corrected QT prolongation (QTc ≥ 440 ms in men and 460 ms in women).
• Child-Pugh's class C liver cirrhosis
• Chronic kidney failure with estimated GFR ≤ 30 ml/min, or ≤ 40 ml/min in patients with concomitant treatment with azithromycin
• Women who are pregnant, breastfeeding, or parturient

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

Sponsors

University Hospital, Angers

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CH Agen

Agen, , France

CHU Amiens

Amiens, , France

CHU Angers

Angers, , France

CH Auxerre

Auxerre, , France

APHP Avicenne

Bobigny, , France

CHU Brest

Brest, , France

CHU Caen

Caen, , France

CH Chalon Sur Saône

Chalon-sur-Saône, , France

CH Cherbroug

Cherbourg, , France

CH Cholet

Cholet, , France

CH Colmar

Colmar, , France

CH Compiègne

Compiègne, , France

APHP Henri Mondor

Créteil, , France

CH Intercommunal Créteil

Créteil, , France

CHU Dijon

Dijon, , France

APHP Joffre Dupuytren

Draveil, , France

CHD Vendée

La Roche-sur-Yon, , France

CH Laval

Laval, , France

CH Le Mans

Le Mans, , France

CH Emile Roux

Le Puy-en-Velay, , France

APHP Emile ROUX

Limeil-Brévannes, , France

CHU Limoges

Limoges, , France

CH Lorient

Lorient, , France

Hôpital Européen - Marseille

Marseille, , France

Hôpital Saint-Joseph

Marseille, , France

CH Melun

Melun, , France

CHU Nantes

Nantes, , France

Hôpital Privé du Confluent

Nantes, , France

CH Niort

Niort, , France

CHR Orléans

Orléans, , France

APHP Saint-Antoine

Paris, , France

GH Croix Saint Simon

Paris, , France

La Pitié-Salpétrière

Paris, , France

CHU Poitiers

Poitiers, , France

CH Pointoise

Pontoise, , France

CH Quimper

Quimper, , France

CH Saint-Brieuc

Saint-Brieuc, , France

CHU Saint-Etienne

Saint-Etienne, , France

CH Saint-Nazaire

Saint-Nazaire, , France

CHU Toulouse

Toulouse, , France

CH Tourcoing

Tourcoing, , France

CHU Tours

Tours, , France

CH Valenciennes

Valenciennes, , France

Clinique Tessier Valenciennes

Valenciennes, , France

CH Vannes

Vannes, , France

CH Versailles

Versailles, , France

CH Princesse Grace

Monaco, , Monaco

Countries

France; Monaco

References

Dubee V, Roy PM, Vielle B, Parot-Schinkel E, Blanchet O, Darsonval A, Lefeuvre C, Abbara C, Boucher S, Devaud E, Robineau O, Rispal P, Guimard T, d'Anglejean E, Diamantis S, Custaud MA, Pellier I, Mercat A; HYCOVID study group; HYCOVID investigators; Angers University Hospital; Cholet Hospital; Laval Hospital; Le Mans Hospital; Tours University Hospital; Quimper Hospital; La Roche sur Yon Hospital; Tourcoing Hospital; Orleans Hospital; Nantes University Hospital; Niort Hospital; Lorient Hospital; Brest University Hospital; Cherbourg Hospital; Saint-Brieuc Hospital; Creteil - APHP University Hospital; Saint-Antoine - APHP University Hospital; Saint-Etienne University Hospital; Toulouse University Hospital; Melun Hospital; Dijon University Hospital; Princesse Grace - Monaco Hospital; Versailles Hospital; Colmar Hospital; Agen-Nerac Hospital; Caen University Hospital; Saint-Nazaire Hospital; Nantes - Confluent Hospital; Limoges University Hospital; Poitiers University Hospital; Amiens University Hospital; Bobigny - APHP University Hospital; Cergy-Pontoise Hospital; Valencienne Hospital; Valencienne - Clinique Tessier Hospital; Henri-Mondor - APHP University Hospital; Chalon-sur-Saone Hospital; Marseille European Hospital; Auxerre Hospital; Diaconnesses Croix-Saint-Simon Hospital; Marseille - Saint Joseph Hospital; HYCOVID management team: Steering committee (authors); HYCOVID management team: Independant data safety and monitoring board; HYCOVID management team: Independent adjudication of clinical events committee; Study management: Coordination; Study management: Data management. Hydroxychloroquine in mild-to-moderate coronavirus disease 2019: a placebo-controlled double blind trial. Clin Microbiol Infect. 2021 Aug;27(8):1124-1130. doi: 10.1016/j.cmi.2021.03.005. Epub 2021 Apr 1.

Reference Type: DERIVED

PMID: 33813110 (View on PubMed)

Other Identifiers

49RC20_0071

Identifier Type: -

Identifier Source: org_study_id