Use of Hydroxychloroquine Alone or Associated for Inpatients With SARS-CoV2 Virus (COVID-19)

Study Overview
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Brief Summary
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The Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV2) has been identified in Wuhan, China, which causes severe pulmonary complications and flu syndrome, which has spread rapidly to all continents. Approximately 25% of hospitalized patients require treatment in intensive care units and 10% require mechanical ventilation. The diagnosis is made by the molecular polymerase chain reaction test. However, diagnostic tests are limited. The clinical care of the patient with COVID-19 is similar to that of patients with severe infectious respiratory complications, consisting of support and oxygen supplementation. Several medications have been tested as remdesivir, a pro-drug nucleoside, which acts by inhibiting viral RNA transcription, although a recently published study has shown no benefit. China recently approved the use of favipiravir, an antiviral used for influenza, as an experimental therapy for COVID-19. Hydroxychloroquine is a drug with great potential treatment, as it can inhibit the pH-dependent steps of replication of various viruses, with a potent effect on SARS-CoV infection and spread. In this way, the present study will evaluate the safety and efficacy of the hydroxychloroquine in patients with symptomatic SARS-Cov2.

Official Title
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Hydroxychloroquine or Hydroxychloroquine Associated With Azithromycin for Inpatients With Moderate or Severe Lung Disease Due to SARS-CoV-2 (COVID-19)

Conditions
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Coronavirus Infections, SARS-CoV 2, SARS (Severe Acute Respiratory Syndrome), Pulmonary Disease

Intervention / Treatment
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* Drug: Hydroxychloroquine Sulfate
* Drug: Hydroxychloroquine Sulfate + Azythromycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged > 18 years; Patients with flu syndrome (fever greater than 37.8C or feverish feeling referred by the patient associated with at least 1 respiratory symptom: cough, difficulty breathing, sputum production, nasal or conjunctival congestion, difficulty swallowing, sore throat, runny nose, signs cyanosis, flapping of the nose and dyspnoea); Diagnosis confirmed by real-time PCR or suspected COVID-19; Hospitalized patients with: Moderate disease: hypoxemia with O2 saturation <93% in room air and / or respiratory rate greater than or equal to 24 incursions per minute and / or radiological evidence of pneumonia with pulmonary impairment less than 50%; or Serious illness: Hospitalized patients with hypoxemia with O2 saturation <93% in room air and / or respiratory rate greater than or equal to 24 incursions per minute with radiological evidence of pneumonia with pulmonary involvement above 50% and / or the presence of sepsis ( organ failure) or need for invasive mechanical ventilation. Exclusion Criteria: Mild cases of flu-like syndrome that do not require hospitalization or O2 saturation greater than or equal to 93% and without radiological evidence of pneumonia; Liver failure or elevation of transaminases greater than 5 times; Cardiac patients with electrocardiogram with extended QT interval; Pregnant women; Use in the last 30 days of hydroxychloroquine or azithromycin; Allergy to hydroxychloroquine or azithromycin.

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Hydroxychloroquine (400 mg) | Drug: Hydroxychloroquine Sulfate<br>* 400 mg orally, every 12 hours x 2 doses (loading dose) and then 400 mg, once daily, orally, for 10 days.<br>* Other names: Reuquinol®;|
| Experimental: Group 2<br>Hydroxychloroquine (400 mg) + azithromycin (500 mg) | Drug: Hydroxychloroquine Sulfate + Azythromycin<br>* 400 mg, orally, every 12 hours x 2 doses (loading dose) and then 400 mg, once a day, orally, for 10 days associated with azithromycin, intravenously or orally, 500 mg / day, for 1 day and then 250mg / day for another 4 days.<br>* Other names: Reuquinol® + Azythromycin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Individual response rate | The individual response rate regarding the World Health Organization Ordinal Scale assessment from basal to 14th Day. | 14 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | All-cause mortality rates at Day 28th after randomization | 28 days after randomization | 
| Duration of mechanical ventilation | Number of days that the patient was on mechanical ventilation which was under ventilation from basal line | baseline | 
| Proportion of patients which needed mechanical ventilation during study | Proportion of patients who do not receive mechanical ventilation at the beginning of the study and then needed mechanical ventilation during hospitalization. | hospitalization within 28 days | 
| World Health Organization (WHO) Ordinal scale | The ordinal scale is an assessment of the clinical status at the first clinical evaluation in a clinical study. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. | 28 days after inclusion and compared to baseline | 
| Duration of hospitalization | Length of hospital stay in days for hospitalization | hospitalization within 28 days | 
| Rates of drug discontinuation | Rates of drug discontinuation in all causes under study | hospitalization within 28 days |