Pragmatic, Double-blind, Placebo-controlled Randomized Clinical Trial, Evaluating Hydroxychloroquine for Prevention of Hospitalization and Respiratory Complications in Non-hospitalized Patients With Confirmed or Probable COVID-19
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,372
- 试验地点
- 69
- 主要终点
- Hospitalization
研究概览
简要总结
In December 2019, a group of patients with pneumonia of unknown cause was identified in Wuhan, in the Hubei province, China. Despite the need of target specific therapeutic options for COVID-19, until now there is no proof of effectiveness of any specific intervention. Some limited observational trials and also evidence from randomized trials have shown no benefit of hydroxychloroquine in inpatient context. Thus, studies evaluating interventions in an outpatient setting in non-severe patients can provide important information related to prognosis and safety. In this way, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine in COVID-19 outpatients by means of a Randomized, double-blind, placebo-controlled trial
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Randomization (1:1) is generated by a validated software and performed in permuted blocks of size 8. Concealment of the randomization list is maintained through a 24-hour, centralized, automated, internet-based randomization system. Furthermore, as placebo-controlled study, the placebo will have the same structural characteristics as the active drug and will be dispensed in cartridges that do not allow the identification of what is being given
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •> 65 years;
- •Hypertension;
- •Diabetes mellitus;
- •COPD or other chronic lung diseases;
- •Immunosuppression;
- •Obesity (Defined as BMI equal to or greater than 30 Kg/m2).
排除标准
- •Patients under 18 years old;
- •Hospitalization at the first medical care;
- •Positive test for influenza at the first medical care;
- •Known hypersensitivity to hydroxychloroquine / chloroquine;
- •Previous diagnosis of retinopathy or macular degeneration;
- •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;
- •Evidence of known liver disease, reported by the patient;
- •Evidence of known chronic kidney disease, reported by the patient;
- •Patients with pancreatitis;
- •Baseline ECG with QTc interval ≥ 480ms;
- •Chronic use of hydroxychloroquine/chloroquine for other reasons;
研究组 & 干预措施
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.
干预措施: Hydroxychloroquine (Drug)
Placebo
The placebo group will follow the same regimen of administration
干预措施: Placebo (Drug)
结局指标
主要结局
Hospitalization
时间窗: 30 days from randomization
To assess if the treatment 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.
次要结局
- Pneumonia(within 30 days from randomization)
- Uncontrolled asthma after ≥ 5 days of starting study medication(within 30 days from randomization)
- Need for Orotracheal Intubation(within 30 days from randomization)
- Otitis media(within 30 days from randomization)
- Time to improve respiratory symptoms(within 30 days from randomization)
- Hospitalization in the Intensive Care Unit(within 30 days from randomization)
- Mortality(within 30 days from randomization)
- Fever resolution time(within 30 days from randomization)
- Mechanical Ventilation Time(within 30 days from randomization)
研究者
Álvaro Avezum Junior
Research Manager - International Research Center
Hospital Alemão Oswaldo Cruz