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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Coronavirus Infections; SARS-CoV 2; Pulmonary Disease; SARS (Severe Acute Respiratory Syndrome)
• Intervention / Treatment: Drug: Hydroxychloroquine Sulfate; Drug: Hydroxychloroquine Sulfate + Azythromycin

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 04753-001
    • Apsen Farmacêutica S.A.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Hydroxychloroquine (400 mg)	Drug: Hydroxychloroquine Sulfate; 400 mg orally, every 12 hours x 2 doses (loading dose) and then 400 mg, once daily, orally, for 10 days.; Other Names: Reuquinol®
Experimental: Group 2; Hydroxychloroquine (400 mg) + azithromycin (500 mg)	Drug: Hydroxychloroquine Sulfate + Azythromycin; 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.; Other Names: Reuquinol® + Azythromycin

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of serious adverse events	Rates of serious adverse events	Day 14th

Collaborators and Investigators

• Sponsor: Apsen Farmaceutica S.A.
• Collaborators: Federal University of São Paulo

Study record dates

Study Major Dates

• Study Start (Anticipated): April 30, 2020
• Primary Completion (Anticipated): November 4, 2020
• Study Completion (Anticipated): November 4, 2020

Study Registration Dates

• First Submitted: April 22, 2020
• First Submitted That Met QC Criteria: April 23, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): November 19, 2020
• Last Update Submitted That Met QC Criteria: November 18, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Severe Acute Respiratory Syndrome; Coronavirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Azithromycin; Hydroxychloroquine
• Other Study ID Numbers: APS000/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No