Efficacy and Safety of Hydroxychloroquine and Ivermectin in Hospitalized no Critical Patients Secondary to COVID-19 Infection: Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 108
- 试验地点
- 1
- 主要终点
- Mean days of hospital stay
研究概览
简要总结
Background: In December 2019, patients with pneumonia secondary to a new subtype of Coronavirus (COVID-19) were identified in China. In a few weeks the virus spread and cases started practically all over the world. In February 2020, the WHO declared a pandemic. Severe symptoms have been found in patients mainly with comorbidities and over 50 years of age. At this time there is no proven therapeutic alternative. In vitro studies and observational experiences showed that antimalarial drugs (Chloroquine and hydroxychloroquine) had antiviral activity and increased viral clearance. Ivermectin, on the other hand, has been shown in vitro to reduce viral replication and in an observational cohort, greater viral clearance with promising clinical results. So far there is no standard of treatment and clinical trials are needed to find effective treatment alternatives. Objective: To evaluate the safety and efficacy of treatment with hydroxychloroquine and ivermectin for serious COVID-19 infections in no critical hospitalized patients. Material and methods: Randomized controlled trial of patients diagnosed with respiratory infection by COVID-19, who present criteria for hospitalization. Randomization will be performed to receive hydroxychloroquine at a dose of 400 mg every 12 hours for one day and then 200 mg every 12 hours, to complete a 5-day treatment schedule. Group 2: Ivermectin 12 mg every 24 hours for one day (less than 80 kg) or Ivermectin 18 mg every 24 hours for one day (greater than 80 kg) + placebo until the fifth day. Group 3: Placebo. Prior to randomization, the risk of cardiovascular complications determined by corrected QT interval, related to hydroxychloroquine intake will be assessed. If the patient is at high risk, the allocation will be to ivermectin only or to placebo in an independent randomization, if the risk is low, any of the three groups could be assigned. Outcomes: The primary outcome will be discharge from hospital for improvement. The safety outcomes will be requirement of mechanical intubation, septic shock or death. Viral clearance will also be evaluated by means of PCR, which will be taken on the 5th day after admission, day 14 and 21.
详细描述
Background In late December 2019, the health authorities of the People's Republic of China reported several cases of pneumonia of unknown origin in Wuhan City, Hubei Province, China. On December 31, 2019, the Chinese Center for Disease Control and Prevention began etiological and epidemiological research on this disease. Three samples of bronchoalveolar lavage were taken from patients from the Jinyintan hospital in Wuhan and through various processes they came to identify a new coronavirus that they initially called on January 7, 2020 as: 2019-nCoV. On January 2020, the World Health Organization (WHO) made the first recommendations on the epidemiological surveillance of this new coronavirus.
On January 22, 2020, the first session of the Emergencies Committee was convened by WHO in Geneva, Switzerland and on January 30 Public Health Emergency of International Importance (ESPII) was declared to the 2019 outbreak.
On February 11, the International Committee on Virus Taxonomy made up of experts, based on the biology, species and type of virus isolated, names this new coronavirus as SARS-CoV-2 and responds to "Severe Acute Respiratory Syndrome Coronavirus 2 "(Severe Acute Respiratory Syndrome CoronaVirus 2 for its acronym in English), the WHO proposes that same day to call the disease caused by SARS-CoV-2 as COVID-19.
The first case reported in Latin America was in Brazil on February 26 and on the 28th of the same month, Mexico communicates its first confirmed case of the new coronavirus in a 35-year-old patient from a trip to Italy. Given the alarming levels of spread and severity of COVID-19, at a press conference on March 11, 2020, WHO Director-General Tedros Adhanom Ghebreyesus declares the SARS-CoV-2.5 outbreak as a pandemic.
IVERMECTIN The SARS-CoV-2 viral genome was rapidly sequenced to allow for a diagnostic test, epidemiological follow-up, and the development of preventive and therapeutic strategies, however, to date there is no evidence from clinical trials for any therapy that improves the evolution of patients suspected or confirmed with COVID-19.
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
- Double (Participant, Care Provider)
盲法说明
Two non-transparent bottles The first bottle will contain the initial treatment: Two ivermectin tablets, two hydroxychloroquine tablets, or two placebo tablets.
The second bottle will contain the follow-up treatment (10 tablets): Two tablets will be indicated, which will be take 12 hours after ingestion of the initial bottle and then one tablet every 12 hours for 4 more days. This bottle will contain placebo and hydroxychloroquine according to the corresponding group.
入排标准
- 年龄范围
- 16 Years 至 90 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •RT-qPCR SARS-CoV-2 positivity or chest computed Tomography with suspected COVID-19 pneumonia
- •Hospitalization by medical emergency staff criteria
排除标准
- •Other confirmed viral active and acute infection
研究组 & 干预措施
Hospitalized patients with COVID-19 QTc < 500 mseg
Patients with confirmed COVID-19 infection by RT-qPCR SARS-CoV-2 or suspected by chest computed tomography with criteria of hospitalization because emergency medical criteria, with no need of critical care assistance. The risk of hydroxychloroquine complications will be assessed by QT corrected by Bazett formula. If QTc < 500 ms could be randomized to hydroxychloroquine, ivermectin or placebo.
干预措施: Hydroxychloroquine (Drug)
Hospitalized patients with COVID-19 QTc < 500 mseg
Patients with confirmed COVID-19 infection by RT-qPCR SARS-CoV-2 or suspected by chest computed tomography with criteria of hospitalization because emergency medical criteria, with no need of critical care assistance. The risk of hydroxychloroquine complications will be assessed by QT corrected by Bazett formula. If QTc < 500 ms could be randomized to hydroxychloroquine, ivermectin or placebo.
干预措施: Ivermectin (Drug)
Hospitalized patients with COVID-19 QTc < 500 mseg
Patients with confirmed COVID-19 infection by RT-qPCR SARS-CoV-2 or suspected by chest computed tomography with criteria of hospitalization because emergency medical criteria, with no need of critical care assistance. The risk of hydroxychloroquine complications will be assessed by QT corrected by Bazett formula. If QTc < 500 ms could be randomized to hydroxychloroquine, ivermectin or placebo.
干预措施: Placebo (Drug)
Hospitalized patients with COVID-19 infection with QTc >500ms
Patients with confirmed COVID-19 infection by RT-qPCR SARS-CoV-2 or suspected by chest computed tomography with criteria of hospitalization because emergency medical criteria, with no need of critical care assistance. The risk of hydroxychloroquine complications will be assessed by QT corrected by Bazett formula. If QTc > 500 ms could be randomized to ivermectin or placebo.
干预措施: Ivermectin (Drug)
Hospitalized patients with COVID-19 infection with QTc >500ms
Patients with confirmed COVID-19 infection by RT-qPCR SARS-CoV-2 or suspected by chest computed tomography with criteria of hospitalization because emergency medical criteria, with no need of critical care assistance. The risk of hydroxychloroquine complications will be assessed by QT corrected by Bazett formula. If QTc > 500 ms could be randomized to ivermectin or placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Mean days of hospital stay
时间窗: Three months
Days from admission as a suspected case of COVID with hospitalization criteria until discharge
Rate of Respiratory deterioration, requirement of invasive mechanical ventilation or dead
时间窗: Three months
Respiratory deterioration defined by respiratory rate \> 25 per minute, requirement of high oxygen supply (FiO2 \> 80% ) to maintain oxygen saturation \> 90 %, invasive mechanical ventilation or dead.
Mean of oxygenation index delta
时间窗: Three months
Daily delta of oxygenation index during the hospitalization
次要结局
- Mean time to viral PCR negativization(5, 14, 21 and 28 days after the first positive PCR)