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

Primary Purpose

Coronavirus

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Hydroxychloroquine
Placebo
Sponsored by
University Hospital, Angers
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronavirus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CH Agen
  • CHU Amiens
  • CHU Angers
  • CH Auxerre
  • APHP Avicenne
  • CHU Brest
  • CHU Caen
  • CH Chalon Sur Saône
  • CH Cherbroug
  • CH Cholet
  • CH Colmar
  • CH Compiègne
  • APHP Henri Mondor
  • CH Intercommunal Créteil
  • CHU Dijon
  • APHP Joffre Dupuytren
  • CHD Vendée
  • CH Laval
  • CH Le Mans
  • CH Emile Roux
  • APHP Emile ROUX
  • CHU Limoges
  • CH Lorient
  • Hôpital Européen - Marseille
  • Hôpital Saint-Joseph
  • CH Melun
  • CHU Nantes
  • Hôpital Privé du Confluent
  • CH Niort
  • CHR Orléans
  • APHP Saint-Antoine
  • GH Croix Saint Simon
  • La Pitié-Salpétrière
  • CHU Poitiers
  • CH Pointoise
  • CH Quimper
  • CH Saint-Brieuc
  • CH Saint-Nazaire
  • CHU Saint-Etienne
  • CHU Toulouse
  • CH Tourcoing
  • CHU Tours
  • CH Valenciennes
  • Clinique Tessier Valenciennes
  • CH Vannes
  • CH Versailles
  • CH Princesse Grace

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Hydroxychloroquine

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Number of death from any cause, or the need for intubation and mechanical ventilation during the 14 days following inclusion and start of treatment.

Secondary Outcome Measures

Number of death from any cause, or the need for intubation and mechanical ventilation during the 28 days following inclusion and start of treatment.
Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 14
WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome
Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 28.
WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome
Number of all-cause mortality at day 14
Number of all-cause mortality at day 28
Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal samples at day 5
Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal samples at day 10
The rate of venous thromboembolic events at day 28, documented and confirmed by an adjudication committee.
Number of all-cause mortality at day 28 in patients aged 75 and older
Clinical evolution on the WHO OSCI scale for COVID-19 between day 0 and day 28 for patients aged 75 or older
Rate of severe adverse events at day 28
Number of all-cause mortality at day 14 in patients aged 75 and older

Full Information

First Posted
March 25, 2020
Last Updated
October 2, 2020
Sponsor
University Hospital, Angers
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1. Study Identification

Unique Protocol Identification Number
NCT04325893
Brief Title
Hydroxychloroquine Versus Placebo in COVID-19 Patients at Risk for Severe Disease
Acronym
HYCOVID
Official Title
Hydroxychloroquine Versus Placebo in Patients Presenting COVID-19 Infection and at Risk of Secondary Complication: a Prospective, Multicentre, Randomised, Double-blind Study
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Terminated
Why Stopped
decrease in number of eligible patients
Study Start Date
April 1, 2020 (Actual)
Primary Completion Date
June 18, 2020 (Actual)
Study Completion Date
June 18, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Angers

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronavirus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
259 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hydroxychloroquine
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of death from any cause, or the need for intubation and mechanical ventilation during the 14 days following inclusion and start of treatment.
Time Frame
Day 14
Secondary Outcome Measure Information:
Title
Number of death from any cause, or the need for intubation and mechanical ventilation during the 28 days following inclusion and start of treatment.
Time Frame
Day 28
Title
Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 14
Description
WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome
Time Frame
Day 14
Title
Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 28.
Description
WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome
Time Frame
Day 28
Title
Number of all-cause mortality at day 14
Time Frame
Day 14
Title
Number of all-cause mortality at day 28
Time Frame
Day 28
Title
Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal samples at day 5
Time Frame
Day 5
Title
Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal samples at day 10
Time Frame
Day 10
Title
The rate of venous thromboembolic events at day 28, documented and confirmed by an adjudication committee.
Time Frame
Day 28
Title
Number of all-cause mortality at day 28 in patients aged 75 and older
Time Frame
day 28
Title
Clinical evolution on the WHO OSCI scale for COVID-19 between day 0 and day 28 for patients aged 75 or older
Time Frame
day 28
Title
Rate of severe adverse events at day 28
Time Frame
day 28
Title
Number of all-cause mortality at day 14 in patients aged 75 and older
Time Frame
day 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
CH Agen
City
Agen
Country
France
Facility Name
CHU Amiens
City
Amiens
Country
France
Facility Name
CHU Angers
City
Angers
Country
France
Facility Name
CH Auxerre
City
Auxerre
Country
France
Facility Name
APHP Avicenne
City
Bobigny
Country
France
Facility Name
CHU Brest
City
Brest
Country
France
Facility Name
CHU Caen
City
Caen
Country
France
Facility Name
CH Chalon Sur Saône
City
Chalon Sur Saône
Country
France
Facility Name
CH Cherbroug
City
Cherbourg
Country
France
Facility Name
CH Cholet
City
Cholet
Country
France
Facility Name
CH Colmar
City
Colmar
Country
France
Facility Name
CH Compiègne
City
Compiègne
Country
France
Facility Name
APHP Henri Mondor
City
Créteil
Country
France
Facility Name
CH Intercommunal Créteil
City
Créteil
Country
France
Facility Name
CHU Dijon
City
Dijon
Country
France
Facility Name
APHP Joffre Dupuytren
City
Draveil
Country
France
Facility Name
CHD Vendée
City
La Roche-sur-Yon
Country
France
Facility Name
CH Laval
City
Laval
Country
France
Facility Name
CH Le Mans
City
Le Mans
Country
France
Facility Name
CH Emile Roux
City
Le Puy-en-Velay
Country
France
Facility Name
APHP Emile ROUX
City
Limeil-Brevannes
Country
France
Facility Name
CHU Limoges
City
Limoges
Country
France
Facility Name
CH Lorient
City
Lorient
Country
France
Facility Name
Hôpital Européen - Marseille
City
Marseille
Country
France
Facility Name
Hôpital Saint-Joseph
City
Marseille
Country
France
Facility Name
CH Melun
City
Melun
Country
France
Facility Name
CHU Nantes
City
Nantes
Country
France
Facility Name
Hôpital Privé du Confluent
City
Nantes
Country
France
Facility Name
CH Niort
City
Niort
Country
France
Facility Name
CHR Orléans
City
Orléans
Country
France
Facility Name
APHP Saint-Antoine
City
Paris
Country
France
Facility Name
GH Croix Saint Simon
City
Paris
Country
France
Facility Name
La Pitié-Salpétrière
City
Paris
Country
France
Facility Name
CHU Poitiers
City
Poitiers
Country
France
Facility Name
CH Pointoise
City
Pontoise
Country
France
Facility Name
CH Quimper
City
Quimper
Country
France
Facility Name
CH Saint-Brieuc
City
Saint-Brieuc
Country
France
Facility Name
CH Saint-Nazaire
City
Saint-Nazaire
Country
France
Facility Name
CHU Saint-Etienne
City
Saint-Étienne
Country
France
Facility Name
CHU Toulouse
City
Toulouse
Country
France
Facility Name
CH Tourcoing
City
Tourcoing
Country
France
Facility Name
CHU Tours
City
Tours
Country
France
Facility Name
CH Valenciennes
City
Valenciennes
Country
France
Facility Name
Clinique Tessier Valenciennes
City
Valenciennes
Country
France
Facility Name
CH Vannes
City
Vannes
Country
France
Facility Name
CH Versailles
City
Versailles
Country
France
Facility Name
CH Princesse Grace
City
Monaco
Country
Monaco

12. IPD Sharing Statement

Citations:
PubMed Identifier
33813110
Citation
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.
Results Reference
derived

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

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