Study Stopped
decrease in number of eligible patients
Hydroxychloroquine Versus Placebo in COVID-19 Patients at Risk for Severe Disease
HYCOVID
1 other identifier
interventional
259
2 countries
47
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Apr 2020
Shorter than P25 for phase_3
47 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 25, 2020
CompletedFirst Posted
Study publicly available on registry
March 30, 2020
CompletedStudy Start
First participant enrolled
April 1, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 18, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
June 18, 2020
CompletedOctober 6, 2020
April 1, 2020
3 months
March 25, 2020
October 2, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Number of death from any cause, or the need for intubation and mechanical ventilation during the 14 days following inclusion and start of treatment.
Day 14
Secondary Outcomes (12)
Number of death from any cause, or the need for intubation and mechanical ventilation during the 28 days following inclusion and start of treatment.
Day 28
Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 14
Day 14
Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 28.
Day 28
Number of all-cause mortality at day 14
Day 14
Number of all-cause mortality at day 28
Day 28
- +7 more secondary outcomes
Study Arms (2)
Hydroxychloroquine
ACTIVE COMPARATORPlacebo
PLACEBO COMPARATORInterventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (47)
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
Related Publications (1)
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.
PMID: 33813110DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER GOV
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 25, 2020
First Posted
March 30, 2020
Study Start
April 1, 2020
Primary Completion
June 18, 2020
Study Completion
June 18, 2020
Last Updated
October 6, 2020
Record last verified: 2020-04