A Prospective, Randomized, Adaptive Phase II/III Clinical Trial, Controlled, Open-label, 3-arms, Parallel, Multi-centred, Chemoprevention of COVID-19: Hydroxychloroquine Post Exposure Prophylaxis For COVID-19
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 93
- 主要终点
- Incidence rate of COVID-19 on day 14 according to positive results of RT-PCR rate at day 14
研究概览
简要总结
Protocol summary
Title
A Prospective, randomized, adaptive phase II/III clinical trial, controlled, open-label, chemoprevention, 3-arms, parallel, multi-centred, to A Prospective, randomized, clinical trial, controlled, open-label, 3-arms, parallel, multi-centred, chemoprevention of COVID-19: Hydroxychloroquine Post Exposure Prophylaxis For COVID-19
Study Periods & Duration of Treatment
Study Duration: 6 months
Approval (IRB and regulatory bodies) 1 month
Recruitment and follow-up: 3 months
Analysis, report writing and submission of publications 1 month This study is a parallel study of one period with an expected duration of treatment (for each subject) of 28 days,
Objectives
- To evaluate if hydroxychloroquine with the proposed dose can provide potent chemoprophylaxis against the development of COVID-19 positive patients in subjects who had primary exposure to COVID-19 positive patients.
- To measure the incidence of potential adverse drug reaction rates for giving hydroxychloroquine for prevention of COVID-19 amongst close contacts
- To provide early analysis of results and redefine sample size accordingly.
- identifying subjects most likely to benefit during the phase II and focusing recruitment efforts on them during phase III
- stopping one arm or the whole trial at an early stage for success or lack of efficacy based on phase II study results
Design
Prospective, Randomized, open-label, three-arm, parallel, adaptive phase II/III controlled study in which subjects will be randomly assigned in a 1:1:1 ratio as per the following:
Arm-1: hydroxychloroquine 800mg (400mg twice daily) given orally on day 1, (loading dose) hydroxychloroquine. Then 400mg (200mg 2 tablets) on day 2,3, 4 and 5.
Arm-2: hydroxychloroquine 400mg (200mg twice daily) Given orally first day (loading dose), then 200mg once daily on day 2,3, 4 and 5.
Arm-3: No Intervention- SARS-CoV-2 surveillance Standard control measures in the country of interest such as self isolation, good personal hygiene and good nutrition.
详细描述
Type of study and design
Prospective, Randomized, open-label, three-arm, parallel, controlled adaptive phase II/III clinical trial in which subjects will be randomly assigned in a 1:1:1 ratio as per the following:
Arm 1 Arm 2 Arm 3 Day 1 HCQ 400 mg (twice daily) HCQ 200 mg (twice daily) Standard measurements of the country until the end of the participation in the study Day 2 HCQ 400 mg (once daily) HCQ 200 mg (once daily) Day 3 HCQ 400 mg (once daily) HCQ 200 mg (once daily) Day 4 HCQ 400 mg (once daily) HCQ 200 mg (once daily) Day 5 HCQ 400 mg (once daily) HCQ 200 mg (once daily)
Amount needed: Plaquenil 200mg: 558 tables per protocol. 42 tablets are needed as preserved supply: total 600 tables.
Randomisation Subjects who meet the eligibility criteria at the study locations will be invited to take part in the study.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Primary contacts, described below, aged 18 to 65 years and having provide Written informed consent by the patient, by the patient's legal /authorized representative as applicable.
- •According to below criteria, as soon as a new subject in identified, he/she will be consented for reaching his contacts according to below criteria. The research team within 48 hours of index case identification will call his/her contacts who fulfill below criteria for participation in the trial. All potential participants will be tested using RT-PCR and IgM and IgG antibodies to rule out current or previous disease status.
- •Contact is a person free from COVID-19 who experienced any one of the following exposures during the 2 days before and the 14 days after the onset of symptoms of a probable or confirmed case:
- •A person living in the same household as a COVID-19 case
- •A person having had direct physical contact with a COVID-19 case (e.g. shaking hands)
- •A person having unprotected direct contact with infectious secretions of a COVID-19 case (e.g. being coughed on, touching used paper tissues with a bare hand)
- •A person having had face-to-face contact with a COVID-19 case within 2 meters [2] and > 15 minutes
- •A person who was in a closed environment (e.g. classroom, meeting room, hospital waiting room, etc.) with a COVID-19 case for 15 minutes or more and at a distance of less than 2 meters
- •A healthcare worker (HCW) or other person providing direct care for a COVID-19 case, or laboratory workers handling specimens from a COVID-19 case without recommended personal protective equipment or with a possible breach of personal protective equipment use policies
- •A contact in an aircraft sitting within two seats (in any direction) of the COVID-19 case, travel companions or persons providing care, and crew members serving in the section of the aircraft where the index case was seated (if severity of symptoms or movement of the case indicate more extensive exposure, passengers seated in the entire section or all passengers on the aircraft may be considered close contacts)
排除标准
- •Women who are pregnant (at the time of screening) or breastfeeding
- •known hypersensitivity or allergy to hydroxychloroquine or other aminoquinoline compounds
- •History of severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis
- •History of pre-existing retinopathy or maculopathy,
- •concomitant use of tamoxifen
- •History of congenital or acquired long QT-interval, current use of drugs that prolong the QT interval,
- •family history of long QT arrythmia, cardiac disease such as heart failure, myocardial infarction
- •concurrent use of anti-arrhythmic drugs, or family history of sudden cardiac death, or sudden cardiac death, bradycardia < 50 beats/min, uncorrected hypokalemia or hypomagnesemia
- •severe renal disease or patients receiving dialysis
- •Patients less than 35 kg bodyweight
- •Currently taking Hydroxychloroquine
- •Suspected or confirmed current COVID-19, defined as: (1) temperature > 38 Celsius; (2) cough; (3) shortness of breath; (4) sore throat; or, if available (not required), (5) positive confirmatory testing for COVID-19
- •Inability to take medications orally
- •Inability to provide written consent
- •With significantly abnormal liver function
- •Participants with psoriasis, myasthenia, hematopoietic and retinal diseases, CNS-related hearing loss;
- •RT-PCR positive for SARS-CoV-2, IgM and IgG antibodies for SARS-CoV-2
- •Currently using another treatment regimen or medication that is being investigated for efficacy in the management of COVID-19.
研究组 & 干预措施
Arm 1 hydroxychloroquine 800mg day 1 and hydroxychloroquine 400mg day 2-5
hydroxychloroquine 800mg (400mg twice daily) given orally on day 1, (loading dose) hydroxychloroquine. Then 400mg (200mg 2 tablets) on day 2,3, 4 and 5.
干预措施: hydroxychloroquine (Drug)
Arm 2 hydroxychloroquine 400mg day 1 and hydroxychloroquine 200mg day 2-5
hydroxychloroquine 400mg (200mg twice daily) Given orally first day (loading dose), then 200mg once daily on day 2,3, 4 and 5.
干预措施: hydroxychloroquine (Drug)
结局指标
主要结局
Incidence rate of COVID-19 on day 14 according to positive results of RT-PCR rate at day 14
时间窗: 14 days
Study will seek to find direct correlation between the administration of Hydroxychloroquine and incidence of COVID-19: A reduced positive RT-PCR samples in subjects who were exposed to COVID-19patients. Positive RT-PCR samples in close contacts on day 14 of randomization.
Safety and adverse events (AEs) incidence rate at day 14
时间窗: 14 days
Safety and adverse events (AEs) incidence rate at day 14
次要结局
- IgM antibodies positive rate for COVID-19 at day 28(28 days)
- Incidence rate of COVID-19 on day 28 according to positive results of RT-PCR rate at day 28(28 days)
- Safety and adverse events (AEs) incidence rate on day 28(28 days)
研究者
Dr Munir Abu-Helalah
Chief Executive Officer
Regional Center for Disease Control and Prevention, Jordan