Hydroxychloroquine Treatment for Severe COVID-19 Pulmonary Infection (HYDRA Trial)

Study Overview
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Brief Summary
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Double blinded randomized clinical trial designed to evaluate the security and efficacy of hydroxychloroquine as treatment for COVID-19 severe respiratory disease. The investigators hypothesize that a 400mg per day dose of hydroxychloroquine for 10 days will reduce all-cause hospital mortality in patients with severe respiratory COVID-19 disease.

Detailed Description
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Since hydroxychloroquine is a low cost and safe anti-malaria drug that has proven effects against COVID-19 in vitro. The investigators aim to study the security and efficacy of this drug in trough a double blinded randomized clinical trial. Recruited patients with severe respiratory disease from COVID-19 will be randomized to an intervention group (400mg per day dose of hydroxychloroquine) and placebo. The investigators' main outcome will be all cause hospital mortality. The investigators hypothesize that a 400mg per day dose of hydroxychloroquine for 10 days will reduce all-cause hospital mortality in patients with severe respiratory COVID-19 disease. Results will be compared in an intention to treat analysis. All clinical, analysis and data team members will be blinded to treatment assignment.

Official Title
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Hydroxychloroquine Treatment for Severe COVID-19 Respiratory Disease: Randomised Clinical Trial (HYDRA Trial)

Conditions
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COVID-19, Severe Acute Respiratory Syndrome

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent negative pregnancy test in women COVID-19 confirmed by rtPCR in any respiratory sample. Severe COVID-19 disease defined as any from the following: Pulse oximetry less than 91% or a 3% drop from base pulse oximetry or need to increase supplementary oxygen in chronic hypoxia Need for mechanical ventilation (invasive or non invasive ) Sepsis/septic shock. Exclusion Criteria: history of anaphylactic shock to hydroxychloroquine. History of previous administration of chloroquine or hydroxychloroquine (within 1 month) decision of attending physician by any reason. History of chronic hepatic disease (Child-Pugh B or C) History of Chronic renal disease (GFR less than 30)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blinded, randomized controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: treatment<br>Hydroxychloroquine tablet 200mg every 12 hours for 10 days. | Drug: Hydroxychloroquine<br>* hydroxychloroquine 400mg day for 10 days<br>|
| Placebo Comparator: placebo<br>identical placebo, one tablet every 12 hours for 10 days | Drug: Placebo oral tablet<br>* Placebo oral tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause hospital mortality | incidence of all-cause mortality | From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to120 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of hospital stay | Days from ER admission to hospital discharge | From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to120 days | 
| Need of mechanical ventilation | need of invasive or non invasive mechanical ventilation | From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to120 days | 
| Ventilator free days | 28 minus days without invasive ventilation support in patients with invasive mechanical ventilation at randomization | From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to120 days | 
| Grade 3-4 adverse reaction | Adverse Reactions | From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to120 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Severe acute respiratory syndrome