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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04325893
Recruitment Status : Recruiting
First Posted : March 30, 2020
Last Update Posted : May 19, 2020
Sponsor:
Information provided by (Responsible Party):
University Hospital, Angers

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.


Condition or disease Intervention/treatment Phase
Coronavirus Drug: Hydroxychloroquine Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Hydroxychloroquine Versus Placebo in Patients Presenting COVID-19 Infection and at Risk of Secondary Complication: a Prospective, Multicentre, Randomised, Double-blind Study
Actual Study Start Date : April 1, 2020
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2020


Arm Intervention/treatment
Active Comparator: Hydroxychloroquine Drug: 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.

Placebo Comparator: Placebo 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.




Primary Outcome Measures :
  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. [ Time Frame: Day 14 ]

Secondary Outcome Measures :
  1. 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 ]
  2. Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 14 [ Time Frame: Day 14 ]
    WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome

  3. Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 28. [ Time Frame: Day 28 ]
    WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome

  4. Number of all-cause mortality at day 14 [ Time Frame: Day 14 ]
  5. Number of all-cause mortality at day 28 [ Time Frame: Day 28 ]
  6. Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal samples at day 5 [ Time Frame: Day 5 ]
  7. Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal samples at day 10 [ Time Frame: Day 10 ]
  8. The rate of venous thromboembolic events at day 28, documented and confirmed by an adjudication committee. [ Time Frame: Day 28 ]
  9. Number of all-cause mortality at day 28 in patients aged 75 and older [ Time Frame: day 28 ]
  10. 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 ]
  11. Rate of severe adverse events at day 28 [ Time Frame: day 28 ]
  12. Number of all-cause mortality at day 14 in patients aged 75 and older [ Time Frame: day 14 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04325893


Contacts
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Contact: Vincent DUBEE 241353872 ext +33 vincent.dubee@chu-angers.fr
Contact: DRCI ANGERS 241353637 ext +33 DRCI-Promotion-Interne@chu-angers.fr

Locations
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Sponsors and Collaborators
University Hospital, Angers
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Responsible Party: University Hospital, Angers
ClinicalTrials.gov Identifier: NCT04325893    
Other Study ID Numbers: 49RC20_0071
First Posted: March 30, 2020    Key Record Dates
Last Update Posted: May 19, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Hydroxychloroquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents