Use of Hydroxychloroquine Alone or Associated for Inpatients With SARS-CoV2 Virus (COVID-19)
Primary Purpose
Coronavirus Infections, SARS-CoV 2, SARS (Severe Acute Respiratory Syndrome)
Status
Withdrawn
Phase
Phase 3
Locations
Brazil
Study Type
Interventional
Intervention
Hydroxychloroquine Sulfate
Hydroxychloroquine Sulfate + Azythromycin
Sponsored by
About this trial
This is an interventional treatment trial for Coronavirus Infections
Eligibility 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.
Sites / Locations
- Apsen Farmacêutica S.A.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Group 1
Group 2
Arm Description
Hydroxychloroquine (400 mg)
Hydroxychloroquine (400 mg) + azithromycin (500 mg)
Outcomes
Primary Outcome Measures
Individual response rate
The individual response rate regarding the World Health Organization Ordinal Scale assessment from basal to 14th Day.
Secondary Outcome Measures
All-cause mortality
All-cause mortality rates at Day 28th after randomization
Duration of mechanical ventilation
Number of days that the patient was on mechanical ventilation which was under ventilation from basal line
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.
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.
Duration of hospitalization
Length of hospital stay in days for hospitalization
Rates of drug discontinuation
Rates of drug discontinuation in all causes under study
Full Information
NCT ID
NCT04361461
First Posted
April 22, 2020
Last Updated
November 18, 2020
Sponsor
Apsen Farmaceutica S.A.
Collaborators
Federal University of São Paulo
1. Study Identification
Unique Protocol Identification Number
NCT04361461
Brief Title
Use of Hydroxychloroquine Alone or Associated for Inpatients With SARS-CoV2 Virus (COVID-19)
Official Title
Hydroxychloroquine or Hydroxychloroquine Associated With Azithromycin for Inpatients With Moderate or Severe Lung Disease Due to SARS-CoV-2 (COVID-19)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Withdrawn
Why Stopped
This study was canceled before enrollment due to a decision by the Sponsor
Study Start Date
April 30, 2020 (Anticipated)
Primary Completion Date
November 4, 2020 (Anticipated)
Study Completion Date
November 4, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Apsen Farmaceutica S.A.
Collaborators
Federal University of São Paulo
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronavirus Infections, SARS-CoV 2, SARS (Severe Acute Respiratory Syndrome), Pulmonary Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1
Arm Type
Experimental
Arm Description
Hydroxychloroquine (400 mg)
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Hydroxychloroquine (400 mg) + azithromycin (500 mg)
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine Sulfate
Other Intervention Name(s)
Reuquinol®
Intervention Description
400 mg orally, every 12 hours x 2 doses (loading dose) and then 400 mg, once daily, orally, for 10 days.
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine Sulfate + Azythromycin
Other Intervention Name(s)
Reuquinol® + Azythromycin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Individual response rate
Description
The individual response rate regarding the World Health Organization Ordinal Scale assessment from basal to 14th Day.
Time Frame
14 days after randomization
Secondary Outcome Measure Information:
Title
All-cause mortality
Description
All-cause mortality rates at Day 28th after randomization
Time Frame
28 days after randomization
Title
Duration of mechanical ventilation
Description
Number of days that the patient was on mechanical ventilation which was under ventilation from basal line
Time Frame
baseline
Title
Proportion of patients which needed mechanical ventilation during study
Description
Proportion of patients who do not receive mechanical ventilation at the beginning of the study and then needed mechanical ventilation during hospitalization.
Time Frame
hospitalization within 28 days
Title
World Health Organization (WHO) Ordinal scale
Description
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.
Time Frame
28 days after inclusion and compared to baseline
Title
Duration of hospitalization
Description
Length of hospital stay in days for hospitalization
Time Frame
hospitalization within 28 days
Title
Rates of drug discontinuation
Description
Rates of drug discontinuation in all causes under study
Time Frame
hospitalization within 28 days
Other Pre-specified Outcome Measures:
Title
Rates of serious adverse events
Description
Rates of serious adverse events
Time Frame
Day 14th
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
Apsen Farmacêutica S.A.
City
São Paulo
ZIP/Postal Code
04753-001
Country
Brazil
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Use of Hydroxychloroquine Alone or Associated for Inpatients With SARS-CoV2 Virus (COVID-19)
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