ChemoPROphyLaxIs For covId-19 Infectious Disease (the PROLIFIC Trial)
试验速览
- 阶段
- 3 期
- 入组人数
- 1,000
- 试验地点
- 1
- 主要终点
- Time to positive COVID-19 disease
研究概览
简要总结
The number of confirmed cases of COVID-19 infectious disease arising from the SARS-CoV-2 coronavirus is rising substantially and rapidly, with the potential to overwhelm the ability of the entire National Health Service (NHS) to cope with the increased demand. The availability of personal protective equipment is limited and reports of high risk procedures such as aerosol generating procedures (e.g. intubation for the sickest patients) is a source of great concern for infection transmission. Frontline NHS staff with direct patient contact have the highest likelihood of exposure to SARS-CoV-2 and development of COVID-19 disease. Efforts to protect these workers from development of COVID-19, using drugs to prevent the disease, require urgent evaluation.
详细描述
The number of confirmed cases of COVID-19 infectious disease arising from the SARS-CoV-2 coronavirus is rising substantially and rapidly, with the potential to overwhelm the ability of the entire National Health Service (NHS) to cope with the increased demand. The availability of personal protective equipment is limited and reports of high risk procedures such as aerosol generating procedures (e.g. intubation for the sickest patients) is a source of great concern for infection transmission. Frontline NHS staff with direct patient contact have the highest likelihood of exposure to SARS-CoV-2 and development of COVID-19 disease. Efforts to protect these workers from development of COVID-19, using drugs to prevent the disease, require urgent evaluation.
This trial will be a double-blind, randomized, placebo-controlled trial in a cohort of frontline healthcare workers, who will potentially be exposed to SARS-CoV-2. Eligible participants will be frontline NHS workers aged 18 to 70 years who work in a healthcare setting with direct patient care. Participants will be randomised to one of 3 arms and receive either: (1) Hydroxychloroquine Daily (loading phase: 800mg for first 2 days; maintenance phase: 1 x 200mg tablet every day) + weekly placebo; (2) Hydroxychloroquine weekly (loading phase: 800mg for first 2 days; maintenance phase: 2 x 200mg tablets every 7th day/weekly) + daily placebo, or (3) placebo (daily and weekly).
Participants will be reviewed at an interim visit 6 weeks after baseline and again and the end of the study treatment in 90 days (approximately 3 months) after randomization. Participants will also complete brief questions about their health weekly while on treatment (remotely, via app/web/phone-based interface).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •To be included in the trial the participant MUST:
- •Have given written informed consent to participate
- •Be aged 18 years to 70 years
- •Not previously have been diagnosed with COVID-19
- •Work in a high-risk secondary or tertiary healthcare setting (hospitals accepting COVID-19 patients) with direct patient-facing care
排除标准
- •The presence of any of the following will mean participants are ineligible:
- •Known COVID-19 positive test at baseline (if available)
- •Symptomatic for possible COVID-19 at baseline
- •Known hypersensitivity reaction to HCQ, chloroquine or 4-aminoquinolines
- •Known retinal disease
- •Known porphyria
- •Known chronic kidney disease (CKD; eGFR<30ml/min)
- •Known epilepsy
- •Known heart failure or conduction problems
- •Known significant liver disease (Gilbert's syndrome is permitted)
- •Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
- •Currently taking any of the following contraindicated medications:
- •Chloroquine
- •Halofantrine
- •Moxifloxacin
- •Cyclosporin
- •Praziquantel
- •Ciprofloxacin
- •Clarithromycin
- •Prochlorperazine
- •Fluconazole
- •Currently taking hydroxychloroquine or having a clinical indication for taking hydroxychloroquine
- •Currently breastfeeding
- •Unable to be followed-up during the trial
- •Current or future involvement in the active treatment phase of other interventional research studies (excluding observational/non-interventional studies) before study follow-up visit
- •Not able to use or have access to a modern phone device/web-based technology
- •Any other clinical reason which may preclude entry in the opinion of the investigator
研究组 & 干预措施
Hydroxychloroquine - Weekly dosing
Hydroxychloroquine weekly (loading phase: 800mg for first 2 days; maintenance phase: 2 x 200mg tablets every 7th day/weekly) + daily placebo, for approximately 90 days.
Route: Oral. Pharmaceutical form: Tablet
干预措施: Hydroxychloroquine - Weekly Dosing (Drug)
Hydroxychloroquine - Daily dosing
Hydroxychloroquine Daily (loading phase: 800mg for first 2 days; maintenance phase: 1 x 200mg tablet every day) + weekly placebo, for approximately 90 days.
Route: Oral. Pharmaceutical form: Tablet
干预措施: Hydroxychloroquine - Daily dosing (Drug)
Placebo
Placebo arm - 2 tablets twice daily for first 2 days (loading phase), followed by 1 tablet every day for 90 days plus 2 tablets every 7th day, for approximately 90 days.
Route: Oral. Pharmaceutical form: Tablet
干预措施: Matched Placebo Hydroxychloroquine (Other)
结局指标
主要结局
Time to positive COVID-19 disease
时间窗: Assessed up to 90 days
Time taken for incidence of COVID-19 disease between Hydroxychloroquine and placebo arms
次要结局
- Number of COVID-19 test positive cases(Assessed up to 90 days)
- Number of COVID-19 serological test positive cases(Assessed up to 90 days)
- Severity of COVID-19 disease between each arm(Assessed up to 90 days)
- Number of common COVID-19 complications between each arm(Assessed up to 90 days)
研究者
Joseph Cheriyan, MD
Dr
Cambridge University Hospitals NHS Foundation Trust