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

• ClinicalTrials.gov Identifier: NCT04361461
• Recruitment Status: Withdrawn
• First Posted: April 24, 2020
• Last Update Posted: November 19, 2020
• Sponsor: Apsen Farmaceutica S.A.
• Collaborator: Federal University of São Paulo
• Information provided by (Responsible Party): Apsen Farmaceutica S.A.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Coronavirus Infections; SARS-CoV 2; SARS (Severe Acute Respiratory Syndrome); Pulmonary Disease	Drug: Hydroxychloroquine Sulfate; Drug: Hydroxychloroquine Sulfate + Azythromycin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hydroxychloroquine or Hydroxychloroquine Associated With Azithromycin for Inpatients With Moderate or Severe Lung Disease Due to SARS-CoV-2 (COVID-19)
• Estimated Study Start Date: April 30, 2020
• Estimated Primary Completion Date: November 4, 2020
• Estimated Study Completion Date: November 4, 2020

Arms and Interventions

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 Name: 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 Name: Reuquinol® + Azythromycin

Outcome Measures

Primary Outcome Measures :

1. Individual response rate [ Time Frame: 14 days after randomization ]
   The individual response rate regarding the World Health Organization Ordinal Scale assessment from basal to 14th Day.

Secondary Outcome Measures :

1. All-cause mortality [ Time Frame: 28 days after randomization ]
   All-cause mortality rates at Day 28th after randomization
2. Duration of mechanical ventilation [ Time Frame: baseline ]
   Number of days that the patient was on mechanical ventilation which was under ventilation from basal line
3. Proportion of patients which needed mechanical ventilation during study [ Time Frame: hospitalization within 28 days ]
   Proportion of patients who do not receive mechanical ventilation at the beginning of the study and then needed mechanical ventilation during hospitalization.
4. World Health Organization (WHO) Ordinal scale [ Time Frame: 28 days after inclusion and compared to baseline ]
   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.
5. Duration of hospitalization [ Time Frame: hospitalization within 28 days ]
   Length of hospital stay in days for hospitalization
6. Rates of drug discontinuation [ Time Frame: hospitalization within 28 days ]
   Rates of drug discontinuation in all causes under study

Other Outcome Measures:

1. Rates of serious adverse events [ Time Frame: Day 14th ]
   Rates of serious adverse events

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Brazil

Apsen Farmacêutica S.A.

São Paulo, Brazil, 04753-001

Sponsors and Collaborators

Apsen Farmaceutica S.A.

Federal University of São Paulo

More Information

• Responsible Party: Apsen Farmaceutica S.A.
• ClinicalTrials.gov Identifier: NCT04361461
• Other Study ID Numbers: APS000/2020
• First Posted: April 24, 2020
• Last Update Posted: November 19, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Hydroxychloroquine; Coronavirus Infections; Severe Acute Respiratory Syndrome; Respiratory Tract Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Azithromycin; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents