Efficacy and Safety of Hydroxychloroquine in Primary Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers at Risk of Exposure: Randomised Control Trial
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 374
- 主要终点
- Prevention of SARS-CoV-2 as determined by negative RT-PCR at the end of 12 week study period
研究概览
简要总结
Healthcare personnel are at an increased risk of exposure to SARS-CoV-2 infection while handling such patients. Currently, there is no treatment available for SARS-CoV-2 and stringent preventive measures are advised to avoid or minimize risk of exposure to healthcare workers. There are in vitro studies available which show inhibition of corona virus by hydroxychloroquine, a widely-used agent against malaria and certain autoimmune conditions and of low-cost and limited toxicity. However, evidence regarding its effects in patients is limited. We plan to conduct a randomized controlled trial to evaluate the safety and potential prophylactic efficacy of hydroxychloroquine in preventing secondary SARS-CoV-2 infection among healthcare workers at high-risk of exposure while managing such patients.
详细描述
An interventional randomised control trial that will include 374 participants who will be healthcare workers at variable risks of exposure to SARS-CoV-2 while managing patients both suspected and confirmed with COVID-19 infection.Each participant will undergo detailed clinical evaluation to confirm eligibility, complete blood count, retinal imaging and ECG rhythm lead at baseline. A nasopharyngeal swab for reverse-transcriptase-polymerase chain reaction (RT-PCR) will also be taken. The enrolled participants will be randomised to two treatment arms with the experimental arm receiving Tab.Hydroxychloroquine (HCQ) 400mg twice a day on day 1 followed by 400mg weekly for 11 weeks. The placebo comparator arm will receive 2 tablets twice daily on day 1 followed by 2 tablets weekly for 11 weeks. The participants will be followed up via phone call weekly to ensure drug compliance, occurrence of drug-related side effects or respiratory symptoms. The final visit 4 will mark the end of study at 12 weeks from randomisation when a repeat nasopharyngeal swab for SARS-CoV-2 RT-PCR will be taken.The primary outcome measures will be prevention of SARS-CoV-2 infection as determined by a negative RT-PCR in the experimental arm at the end of 12 weeks and HCQ safety as determined by occurrence of adverse events.
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 blinding
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult healthcare workers all genders ≥ 18 to ≤ 60 years of age upon study consent.
- •Healthcare workers (doctors and nurses) at Services hospital, Lahore considered work at high-risk of SARS-CoV-2 exposure (defined below):
- •Healthcare workers in Corona triage areas.
- •Healthcare workers in Corona Isolation Units.
- •Healthcare workers in Corona ICUs.
- •Healthcare workers in general medical wards.
- •Healthcare workers in general surgical wards.
- •Healthcare workers in other units not directly dealing with suspected Corona patients e.g. Endocrinology department
- •Afebrile with no constitutional symptoms.
- •No household contact with confirmed active SARS-CoV-2 infection in the last 3 weeks.
- •Negative PCR at visit
- •Willing and able to comply with scheduled visits, treatment plan, and other study procedures.
- •Willing to not take any other medicines especially fluoroquinolones and macrolides for the duration of study.
- •Signed informed consent, demonstrating that the subject understands the interventions required for the study and the purpose of the study.
排除标准
- •Participation in other investigational clinical trials for the treatment or prevention of SARS-CoV-2 infection within 30days.
- •Subjects unwilling to practice at least one highly effective method of birth control for the duration of the study.
- •Having a prior history of blood disorders such as aplastic anemia, agranulocytosis, leukopenia, or thrombocytopenia or prior history of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.
- •Having H/O skin disorders e.g. dermatitis, psoriasis or porphyria.
- •Taking any of the following medication:
- •Anti-arrythmic agents including digoxin.
- •GI drugs including antacids, proton-pump inhibitors, cimetidine.
- •Anti-cancer treatment including methotrexate, cyclosporin.
- •Anti-diabetic agents including insulin.
- •Corticosteroids.
- •Drugs causing QT interval prolongation especially antidepressants, anti-epileptics and macrolides.
- •Drugs affecting electrolyte balance including diuretics, laxatives.
- •Drug allergies: 4-Aminoquinolines.
- •Pre-existing retinopathy/maculopathy of the eye.
- •Known chronic liver disease or cirrhosis, including hepatitis B and/or untreated hepatitis.
- •Previous history of severe hypoglycaemia.
- •Known case of renal disease.
- •Untreated or uncontrolled active bacterial, fungal infection.
- •Known or suspected active drug or alcohol abuse.
- •Women who are pregnant or breastfeeding.
- •Known hypersensitivity to any component of the study drug.
- •A known history of prolonged QT syndrome or history of additional risk factors for arrythmias (e.g., heart failure, family history of Long QT Syndrome).
- •Known H/O respiratory disorders e.g. asthma, chronic obstructive pulmonary disease.
研究组 & 干预措施
Treatment group
Health care workers at high risk of contracting SARS-CoV-2 randomized to this arm will be treated with oral hydroxychloroquine 400 mg twice a day (four 200 mg tablets) on day 1 followed by 400mg (two 200 mg tablets) once a week for 11 weeks.
干预措施: Hydroxychloroquine (Drug)
Control group
Health care workers at high risk of contracting SARS-CoV-2 randomized to this arm will be treated with placebo twice a day (four tablets) on day 1 followed by 2 tablets once a week for 11weeks.
干预措施: Placebo oral tablet (Drug)
结局指标
主要结局
Prevention of SARS-CoV-2 as determined by negative RT-PCR at the end of 12 week study period
时间窗: From date of randomization until study completion 12 weeks after treatment initiation
Negative RT-PCR for SARS-CoV-2 both at baseline and at end of 12 weeks in experimental arm
Safety as determined by presence or absence of any adverse event related with hydroxychloroquine treatment
时间窗: From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiation
To assess the presence or absence of side effects from HCQ treatment.
次要结局
- Incidence of any acute respiratory infection(From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiation)
- Confirmed SARS-CoV-2 infection based on symptoms and confirmed by RT-PCR(From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiation)
- Clinical disease severity in confirmed SARS-CoV-2 participants(From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiation)
研究者
Dr. Saira Burney
Doctor
Services Institute of Medical Sciences, Pakistan