Hydroxychloroquine Post-Exposure Prophylaxis for Coronavirus Disease (COVID-19) Among Health-Care Workers: A Randomized-Controlled Trial
试验速览
- 阶段
- 不适用
- 入组人数
- 582
- 试验地点
- 1
- 主要终点
- Clinical COVID-19
研究概览
简要总结
Background: The rapid spread and high infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) makes identifying an effective prophylaxis agent highly important. One of the important target populations for such intervention who are at high risk of exposure are health care workers (HCWs) who may develop disease and/or expose patients and other HCWs. Hydroxychloroquine (HCQ), currently in usage for treatment of severe Coronavirus Disease 2019 (COVID-19), has in addition to in-vitro activities of inhibition of virus replication and immunomodulation, an important role in the inhibition of pre-entry step of the virus to host cells. Such activity in the early stage of infection may play a role in prevention of disease progression.
Objectives: To evaluate the effect of HCQ in prevention of clinical disease and reduction of viral shedding among HCWs following exposure to confirmed COVID-19 patients.
Study design: Multi-center, randomized controlled, superiority, open label trial Setting: The study will be conducted at Rambam Health Care Campus. Eligibility: Participants eligible for inclusion will include non-pregnant adult (>18 years old) HCWs who were exposed to a confirmed case of COVID-19 without full adherence to droplet precautions. Participants will be eligible in a period no longer than 72 hours after exposure.
Intervention: HCQ will be given in the intervention group in a dosage regimen of 400mg BID in the first day followed by 200mg BID for overall 10 days. Participants in the control group will receive no treatment. Treatment will be started no longer than 72 hours following exposure.
Outcomes: The primary outcome will be the number of participants who develop clinical signs compatible with COVID 19 (defined in full protocol) within 14 days of exposure. Secondary outcomes will include virologically-confirmed COVID 19, disease severity (need for hospitalization, mechanical ventilation and 30-day mortality) and viral shedding duration (time between first positive PCR to last of two consecutive negative tests) for confirmed COVID 19 cases.
Sample size: The trial will test for HCQ's superiority assuming a primary outcome incidence of 20% in the control group and a reduction of 50% with HCQ. The sample size required for a power of 80% (alpha 0.05) is 291 participants per each group.
详细描述
BACKGROUND:
A novel coronavirus referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) was identified as the causative agent for the pandemic coronavirus disease 2019 (COVID-19). While in most cases, COVID-19 is a mild disease, in almost 15% of cases it may cause a severe disease leading to respiratory failure, septic shock, multi-organ failure and death. The relatively high ratios of severe morbidity and mortality that occurs during a short period led to an extremely high burden on health systems as expected in pandemics. Health care personnel work long hours in a highly intensive work environment, increasing the risk of exposure to SARS CoV-2 infection. In China, almost 4% of COVID-19 cases were of health care staff, having severe disease in 15% of them. In Italy, more than two thousands health care workers (HCWs) were diagnosed with COVID-19 consisting 9% of total confirmed cases up to 15 of March, 2020.
Accumulating data suggest that the most likely mode of transmission of SARS CoV-2 is by droplets, either by inhalation or by contact. Person to person transmission was identified from asymptomatic infected cases that were redefined recently as pre-symptomatic cases. Most health agencies suggest a careful approach regarding the protection of HCWs. Still, accidental exposure of HCWs to COVID-19 cases occurs. Such exposure may occur in many scenarios, either in the context of unprotected contact with unsuspected cases or inappropriate protection in contact with suspected or confirmed cases of COVID-19. Exposure of HCW to a COVID-19 case necessitates risk stratification of disease transmission. The CDC defines the risk as high if a prolonged contact ("few minutes in a distance of 6 feet) happened while the patient and the HCW did not wear a facemask. A medium risk is defined if either the patient did not wear a facemask but HCW was with facemask but without eye protection or a patient was wearing a facemask but the HCW was not. In both situations of high and medium risk exposures, exclusion from work for 14 days after last exposure is recommended.
Both HCWs safety and the critical demand for human resources in COVID-19 pandemic makes the possibility of effective post exposure prophylaxis highly important.
Chroloquine/hydroxychloroquine for prophylaxis of SARS-CoV2:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult participant (>18 years)
- •HCW who had a contact without adequate personal protective equipment (PPE) with a confirmed COVID-19 patient.
- •Time between exposure to randomization no longer than 72 hours.
- •Informed consent from participant
排除标准
- •Symptoms compatible with COVID-19 upon randomization
- •Known allergy to HCQ or chloroquine
- •History of any arrhythmia.
- •Severely reduced LV function (Ejection fraction<30%)
- •Retinopathy
- •Pregnancy or breast feeding
- •Concomitant treatment with azithromycin, flecainide, amiodarone, digoxin, procainamide, propafenone, thioridazine, pimozide.
- •Chronic chloroquine/ HCQ treatment
研究组 & 干预措施
intervention group
participants will recieve hydroxychloroquine in a dosage regimen of 400mg BID in the first day followed by 200mg BID for overall 10 days.
干预措施: Hydroxychloroquine (Drug)
结局指标
主要结局
Clinical COVID-19
时间窗: 14 days following exposure.
Number of patients developing clinical symptoms and signs compatible with COVID-19 following exposure
次要结局
- Confirmed COVID-19(14 days following exposure.)
- Time to virological recovery(30 days)
- Time to symptoms onset(14 days)
- Development of pneumonia(14 days)
- Development of severe disease(14 days)
- Need for hospitalization or ICU(14 days)
- Adverse events(14 days)
- Time to de-isolation(30 days)
- Mortality(30 days)
研究者
Nesrin Ghanem-Zoubi MD
Infectious Diseases Institute senior physician
Rambam Health Care Campus