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临床试验/NCT04446104
NCT04446104已完成3 期

A Randomized Open-label Prophylaxis Trial Among Migrant Workers at High-risk of COVID-19 (DORM Trial)

National University Hospital, Singapore1 个研究点 分布在 1 个国家目标入组 4,257 人开始时间: 2020年5月13日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
3 期
状态
已完成
入组人数
4,257
试验地点
1
主要终点
Laboratory-confirmed COVID-19 in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)

研究概览

简要总结

In December 2019, a novel coronavirus, now called COVID-19, emerged as a global health threat from Wuhan, China. Within weeks, the contagious virus spread within and between communities, causing a lower respiratory tract infection dominated by symptoms of fever, cough and sore throat. The incubation period was estimated at between 5 to 7 days, but could last as long as 14 days. Although COVID-19 causes a mostly mild and self-limiting disease, respiratory involvement has been reported in about 5% of the population, requiring supplemental oxygen and even ventilatory support to relieve hypoxia. Alveolar damage, fibrosis and consolidation have been reported in radiologic and post-mortem studies. Existing data suggest a mortality rate of COVID-19 is approximately 1-2%, higher among individuals with pre-existing comorbidities and in healthcare systems with suboptimal access to ventilatory support.

Given its high transmissibility, COVID-19 has quickly spread across the globe within a short interval. By 27 April 2020, over 3 million people around the world have been diagnosed with COVID-19, and more 200,000 have succumbed to the disease. As a proportion of patients manifest mild or no symptoms, these numbers are likely an underestimate of the actual number of patients with COVID-19. More disconcertingly, patients are known to shed viruses despite mild or no symptoms, making it essential that a collective approach against COVID-19 incorporate active pharmacological treatment to prevent or mitigate virus pathogenesis prior to its potential evolution to cause respiratory distress. To date, clinical trials have focused on the treatment of hospitalised patients diagnosed with COVID-19; only few have examined the clinical benefits of pharmacological agents despite few compelling in vitro data.

The relatively high transmission of COVID-19 in a closed dormitory environment of migrant workers in Singapore presents a real-life scenario where a prophylaxis treatment could reduce the impact of the disease. In Singapore, there are well grounded concerns an excess in cases could pose the possibility of strain in healthcare system and mentally drain her workers. The availability of an effective prophylaxis treatment is highly desirable to potentially reduce this burden. Data from the current study could also have implications on how future outbreaks in high-density areas should be managed, especially when residents are subjected to quarantine and isolation.

详细描述

This is a pragmatic, open-label, randomised study with 4 interventional and 1 control arms. Individuals will be recruited from migrant worker dormitories, and written informed consent taken prior to enrolment. Randomisation will be done by the level within the dormitory building and predetermined each day according to a randomisation schema done by an independent statistician. This will obviate the potential for bias due to drug exchange between study individuals.

The 5 arms consist of:

  • Experimental arms
  1. Hydroxychloroquine tablet 400mg loading dose, followed by 200mg daily for 42 days (1,000 study subjects)
  2. Ivermectin tablet 12mg single dose (1,000 study subjects)
  3. Zinc tablet 80 mg/vitamin C 500mg daily for 42 days (1,000 study subjects)
  4. Povidone-iodine throat spray (3 times daily) for 42 days (1,000 study subjects)
  • Control arm 5) Vitamin C tablet 500mg daily for 42 days (1,000 study subjects)

Study information sheet will be circulated in selected buildings within the dormitory 1-4 days before recruitment starts. All publicity materials and informed consent form will be translated to the different languages (e.g. Tamil, Bengali, Chinese, Burmese and Malay). A translator will be present to aid translation if necessary. Study subjects will be given ample time to ask questions relating to the study. Prospective participants will respond by showing up to recruitment stations at designated dates and times. Facilitators from the dormitory will be engaged to assist with the ground crowd-control. Prospective videos will be shown to inform the subject on the purpose, study inclusion and exclusion criteria, study medications, blood taking, reporting of adverse effects and follow-up visits. Informed consent will be taken before all study-related procedures are performed, including study eligibility. Translators will also help translate the daily questionnaires.

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
21 Years 至 60 Years(Adult)
性别
Male
接受健康志愿者

入选标准

  • Subjects must meet all the of following criteria to be included in this study:
  • Men residing in dormitory aged 21-60 years
  • Willing and able to give informed consent
  • Able to understand instructions and consume study medications according to the study protocol.
  • Weight more than 40kg
  • Owns a mobile phone (with wireless fidelity and/or 3G connection and able to fill in online forms.

排除标准

  • Subjects who have any of the following criteria at baseline will be excluded from participating in this study:
  • Symptoms of acute respiratory illness (e.g. fever, runny nose, sore throat, cough, breathlessness, loss of smell and loss of taste) for the past 30 days
  • Known current or history of SARS-CoV-2 infection
  • Unable to read English or any of the available local languages used for this clinical trial
  • History of cardiac or neurological diseases
  • History of retinal diseases
  • History of diabetes on insulin treatment
  • History of depression
  • History of chronic alcohol use
  • History of renal or hepatic dysfunction
  • History of glucose-6-phosphate dehydrogenase deficiency
  • History of anaemia, after exposure to any given medications
  • History of thyroid disorder, hyperthyroidism, or sensitivity to iodine
  • History of allergies with systemic presentation to any given medication (e.g.: swelling of the face, throat, eyes and lips, respiratory disturbances, asthmatic attacks, widespread skin blistering or urticaria (hives))
  • Concomitant medication that may lead to cardiac arrhythmia (azithromycin, amitriptyline, cimetidine, citalopram, nortriptyline, pantoprazole, quetiapine etc).
  • Unwilling to comply with study dosing, instructions or restrictions.

研究组 & 干预措施

Hydroxychloroquine

Experimental

Participants will receive hydroxychloroquine tablet 400mg loading dose, followed by 200mg daily for 42 days

干预措施: Hydroxychloroquine Sulfate Tablets (Drug)

Ivermectin

Experimental

Participants will receive ivermectin tablet 12mg single dose

干预措施: Ivermectin 3mg Tab (Drug)

Zinc/ Vitamin C

Experimental

Participants will receive zinc tablet 80 mg/vitamin C 500mg daily for 42 days

干预措施: Zinc (Drug)

Povidone-iodine throat spray

Experimental

Participants will receive povidone-iodine throat spray (3 times daily) for 42 days

干预措施: Povidone-Iodine (Drug)

Vitamin C

Active Comparator

Participants will receive vitamin C tablet 500mg daily for 42 days

干预措施: Vitamin C (Dietary Supplement)

结局指标

主要结局

Laboratory-confirmed COVID-19 in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)

时间窗: At the end of study dosing, which is day 42

次要结局

  • Acute respiratory illness in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)(At the end of study dosing, which is day 42)
  • Rate of oxygen supplementation and mechanical ventilation in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)(At the end of study dosing, which is day 42)
  • Duration of oxygen supplementation and mechanical ventilation in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)(At the end of study dosing, which is day 42)
  • Adverse events and serious adverse events in control arm (Vitamin C)(At the end of study dosing, which is day 42)
  • Drug discontinuation due to adverse events in control arm (Vitamin C)(At the end of study dosing, which is day 42)
  • Rate of laboratory-confirmed COVID-19 in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)(At the end of study dosing, which is day 42)
  • Length of hospital stay in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)(At the end of study dosing, which is day 42)
  • Febrile respiratory illness in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)(At the end of study dosing, which is day 42)
  • Rate of hospitalization for COVID-19 and non-COVID-19 related indications in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)(At the end of study dosing, which is day 42)

研究者

申办方类型
Other
责任方
Sponsor

研究点 (1)

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