Randomized Placebo-controlled Trial of Hydroxychloroquine in Outpatient Cases With Coronavirus Disease 2019 (COVID-19)
Keywords
Abstract
Description
Pragmatic, double-blind, placebo-controlled randomized parallel-group, two-arm clinical trial (with allocation ratio 1:1), evaluating hydroxychloroquine (800 mg at 1st day, and 400 mg from day 2 to 7) for prevention of hospitalization and respiratory complications in non-hospitalized confirmed or suspected COVID-19 cases. Key inclusion criteria are adults (equal to or greater tahn 18 years) seeking medical care with suspected or confirmed COVID-19, with time between symptoms and inclusion ≤ 07 days, presenting mild symptoms, without indication of hospitalization and at least one risk factor for complication (> 65 years; hypertension; diabetes mellitus; asthma; Chronic Obstructive Pulmonary Disease (COPD) or other chronic lung diseases; smoking; immunosuppression; obesity (Defined as BMI equal to or greater than 30 Kg/m2). Primary endpoint is to assess if the treatment with hydroxychloroquine is able to avoid hospitalization due to a COVID-19-related clinical reason within 30 days of randomization in an outpatient setting. Hospitalization is considered to be hospital stay for a period > 24h or an additional hospitalized calendar day. The primary endpoint is centrally adjudicated by an independent clinical events committee blinded to the assigned treatment groups. Secondary endpoints include uncontrolled asthma after ≥ 5 days of starting study medication; pneumonia; otitis media; fever resolution time; time to improve respiratory symptoms; hospitalization in the Intensive Care Unit; need for orotracheal intubation; mechanical ventilation time; mortality. Safety outcomes will be hypoglycemia; palpitations; reduced visual acuity; diarrhea; anorexia; and emotional lability. The evaluation of the primary outcome (hospitalization within 30 days) will be performed for the included population following the principle of intention-to-treat (ITT), which will consist of all randomized cases. A modified intention-to-treat analysis (mITT), in which cases definitely confirmed as negative for COVID-19 will be excluded, will also be performed.
Dates
| Last Verified: | 06/30/2020 |
| First Submitted: | 07/02/2020 |
| Estimated Enrollment Submitted: | 07/08/2020 |
| First Posted: | 07/09/2020 |
| Last Update Submitted: | 07/08/2020 |
| Last Update Posted: | 07/09/2020 |
| Actual Study Start Date: | 05/11/2020 |
| Estimated Primary Completion Date: | 08/29/2020 |
| Estimated Study Completion Date: | 12/29/2020 |
Condition or disease
Intervention/treatment
Drug: Hydroxychloroquine (HCQ)
Drug: Placebo
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Hydroxychloroquine (HCQ) HCQ group participants will receive a dose of 400mg twice daily (BID) in the first day, and a dose of 400 mg once daily (OD) from the second day of treatment, in a total of 7 days. | Drug: Hydroxychloroquine (HCQ) Hydroxychloroquine pharmaceutical form will be tablets of 400 mg. |
| Placebo Comparator: Placebo The placebo group will follow the same regimen of administration | Drug: Placebo Hydroxychloroquine placebo |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: It will be considered eligible those adults (equal to or greater than 18 years) seeking medical care with suspected or confirmed COVID-19, with time between symptoms and inclusion ≤ 07 days, presenting mild symptoms, without indication of hospitalization and at least 1 risk factor for complication: 1. > 65 years; 2. Hypertension; 3. Diabetes mellitus; 4. Asthma; 5. COPD or other chronic lung diseases; 6. Smoking; 7. Immunosuppression; 8. Obesity (Defined as BMI equal to or greater than 30 Kg/m2). Exclusion Criteria: 1. Patients under 18 years old; 2. Hospitalization at the first medical care; 3. Positive test for influenza at the first medical care; 4. Known hypersensitivity to hydroxychloroquine / chloroquine; 5. Previous diagnosis of retinopathy or macular degeneration; 6. Previous diagnosis of Long QT-syndrome, history of sudden death in close family members (parents and siblings), decompensated heart failure, unstable coronary artery disease, use of anti-arrhythmic drugs or other drugs that can increase the hydroxychloroquine bioavailability or enhance its effect; 7. Evidence of known liver disease, reported by the patient; 8. Evidence of known chronic kidney disease, reported by the patient; 9. Patients with pancreatitis; 10. Baseline ECG with QTc interval ≥ 480ms; 11. Chronic use of hydroxychloroquine/chloroquine for other reasons; 12. Pregnancy. |
Outcome
Primary Outcome Measures
1. Hospitalization [30 days from randomization]
Secondary Outcome Measures
1. Uncontrolled asthma after ≥ 5 days of starting study medication [within 30 days from randomization]
2. Pneumonia [within 30 days from randomization]
3. Otitis media [within 30 days from randomization]
4. Fever resolution time [within 30 days from randomization]
5. Time to improve respiratory symptoms [within 30 days from randomization]
6. Hospitalization in the Intensive Care Unit [within 30 days from randomization]
7. Need for Orotracheal Intubation [within 30 days from randomization]
8. Mechanical Ventilation Time [within 30 days from randomization]
9. Mortality [within 30 days from randomization]
Other Outcome Measures
1. Hypoglycemia [within 30 days from randomization]
2. Palpitations [within 30 days from randomization]
3. Reduced visual acuity [within 30 days from randomization]
4. Diarrhea [within 30 days from randomization]
5. Anorexia [within 30 days from randomization]
6. Emotional lability [within 30 days from randomization]
7. Time to hospitalization after randomization [within 30 days from randomization]
8. Assessment of the patient clinical status at the time of hospitalization [within 30 days from randomization]
