Chemoprophylaxis of SARS-CoV-2 Infection (COVID-19) in Exposed Healthcare Workers : A Randomized Double-blind Placebo-controlled Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 118
- 试验地点
- 9
- 主要终点
- Occurrence of an symptomatic or asymptomatic SARS-CoV-2 infection among healthcare workers (HCWs)
研究概览
简要总结
Since December 2019, the emergence of a new coronavirus named SARS-Cov-2 in the city of Wuhan in China has been responsible for a major epidemic of respiratory infections, including severe pneumonia. Within weeks, COVID-19 became a pandemic.
In the absence of specific antiviral treatment, a special attention should be given to prevention. Personal protection equipments may be insufficiently protective, including in healthcare workers, a significant proportion of whom (around 4%) having been infected in the outbreaks described in China and more recently in Italy. Infection in healthcare workers could result from the contact with COVID-19 people in community or with infected colleagues or patients.
As it will take at least a year before vaccines against SARS-CoV-2 becomes available, chemoprophylaxis is an option that should be considered in this setting where prevention of SARS-CoV-2 infection in Health Care Workers.
The COVIDAXIS trial evaluates a chemoprophylaxis of SARS-CoV-2 infection in Health Care Workers. This trial is divided into two distinct studies that could start independently each with its own randomization process: COVIDAXIS 1 will study Hydroxychloroquine (HCQ) versus placebo; COVIDAXIS 2 will study Lopinavir/ritonavir (LPV/r) versus placebo.
Upon randomization healthcare workers (HCWs) involved in the management of suspected or confirmed COVID-19 cases will be assigned to one of the following 2 treatment groups:
详细描述
The study COVIDAXIS 1(Hydroxychloroquine (HCQ) versus placebo) will be realized on 600 participants and will be implemented first in as many centers as possible.
Upon randomization, with 1:1 allocation ratio, healthcare workers involved in the management of suspected or confirmed COVID-19 cases will be assigned to one of the following 2 treatment groups:
- Group 1.1: HCQ 200 mg : 2 tablets on the evening at Day 1 and 2 tablets on the morning at Day 2 and 1 tablet once daily afterwards
- Group 1.2: Placebo of HCQ, 2 tablets on the evening at Day 1 and 2 tablets on the morning at Day 2 and 1 tablet once daily afterwards.
The COVIDAXIS 2 (Lopinavir/ritonavir (LPV/r) versus placebo will be realized on 600 participants and will be implemented in already participating and newer centers in a second step (when LPV/r becomes available).
Upon randomization, with 1:1 allocation ratio, healthcare workers involved in the management of suspected or confirmed COVID-19 cases will be assigned to one of the following 2 treatment groups:
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
- Triple (Participant, Investigator, Outcomes Assessor)
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 healthcare workers (HCWs) (for instance physicians, nurses, assistant nurses, dentists, physiotherapists, midwives, etc.)
- •HCW involved at the time of enrolment in the care and the management of patients with confirmed or suspected SARS-CoV-2 infection in hospital settings, in outpatient care settings or in geriatric long-term care facilities. These HCWs have prolonged or repeated close contact to these patients.
- •HCW tested negative for HIV
- •HCW affiliated to the French health insurance system
- •HCW women of childbearing age with an effective contraception (ethinylestradiol-containing contraceptive pills are not regarded as effective in the context of LPV/r treatment - COVIDAXIS 2)
- •Willing to comply to study design and the follow-up
- •Consent form signed
排除标准
- •For COVIDAXIS 1:
- •HCW with positive SARS-CoV-2 RT-PCR of nasopharyngeal swab at the inclusion visit.
- •HCW with past history of confirmed SARS-CoV-2 infection
- •HCW with positive SARS-CoV-2 serology at the inclusion visit
- •HCW with comorbidities such as hypothyroidism that need hormonal substitution, or retinopathy or with prior intermittent porphyria, or chronic renal failure (glomerular filtration rate < 30mL/min) or prior hepatic failure or psoriasis.
- •HCW with prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency
- •HCW with known hypersensitivity/allergy to HCQ
- •HCW with baseline QTc interval > 450ms in men or > 460ms in women and QTc <320 ms (both gender)
- •HCW with personal or family history of long QT syndrome, torsades de pointes, or sudden death
- •Pregnant HCW
- •Breastfeeding HCW
- •HCW taking comedications known to have interactions with HCQ according to the official characteristics of the product
- •For COVIDAXIS 2:
- •HCW with positive SARS-CoV-2 RT-PCR of nasopharyngeal swab at the inclusion visit.
- •HCW with past history of confirmed SARS-CoV-2 infection
- •HCW with positive SARS-CoV-2 serology at the inclusion visit
- •HCW with comorbidities such as chronic HCV infection treated by direct antiviral drugs or with hypothyroidism that need hormonal substitution, or known to have hypercholesterolemia hypertriglyceridemiaor chronic renal failure (glomerular filtration rate < 30mL/min) or prior hepatic failure
- •HCW with known hypersensitivity/allergy to LPV/r
- •HCW with baseline QTc interval > 450ms in men or > 460ms in women and QTc <320 ms (both gender)
- •HCW with personal or family history of long QT syndrome, torsades de pointes, or sudden death
- •Pregnant HCW
- •Breastfeeding HCW
- •HCW taking comedications known to have interactions with LPV/r according to the official characteristics of the product
研究组 & 干预措施
Hydroxychloroquine (HCQ) vs Placebo
Group 1.1: HCQ 200 mg : 2 tablets on the evening at Day 1 and 2 tablets on the morning at Day 2 and 1 tablet once daily afterwards
Group 1.2: Placebo of HCQ, 2 tablets on the evening at Day 1 and 2 tablets on the morning at Day 2 and 1 tablet once daily afterwards.
干预措施: Hydroxychloroquine (Drug)
Hydroxychloroquine (HCQ) vs Placebo
Group 1.1: HCQ 200 mg : 2 tablets on the evening at Day 1 and 2 tablets on the morning at Day 2 and 1 tablet once daily afterwards
Group 1.2: Placebo of HCQ, 2 tablets on the evening at Day 1 and 2 tablets on the morning at Day 2 and 1 tablet once daily afterwards.
干预措施: Placebo of Hydroxychloroquine (Drug)
Lopinavir/ritonavir (LPV/r) vs Placebo
Group 2.1: LPV/r 200/50 mg, 2 tablets twice daily
Group 2.2: Placebo of LPV/r, 2 tablets twice daily
干预措施: Lopinavir and ritonavir (Drug)
Lopinavir/ritonavir (LPV/r) vs Placebo
Group 2.1: LPV/r 200/50 mg, 2 tablets twice daily
Group 2.2: Placebo of LPV/r, 2 tablets twice daily
干预措施: Placebo of LPV/r Tablets (Drug)
结局指标
主要结局
Occurrence of an symptomatic or asymptomatic SARS-CoV-2 infection among healthcare workers (HCWs)
时间窗: Up to 2.5 months
An infection by SARS-CoV-2 is defined by either: * a positive specific Reverse Transcription - Polymerase Chain Reaction (RT-PCR) on periodic systematic nasopharyngeal swab during follow-up OR * a positive specific RT-PCR on a respiratory sample in case of onset of symptoms consistent with COVID-19 during follow-up OR * a seroconversion to SARS-CoV-2 after randomization.
次要结局
- Evaluation of the incidence of severe cases of SARS-CoV-2 infection in each arm.(Up to 2.5 months)
- corrected QT interval (ms)(At baseline, at D2 (only for COVIDAXIS 1) and every week up to 2 months.)
- Evaluation of the occurrence of adverse events in each arm,(Up to 2.5 months)
- Evaluation of the discontinuation rates of the investigational drug in each arm,(Up to 2 months)
- Evaluation of the adherence of participants to study drug,(Up to 2 months)
- Evaluation of the incidence of symptomatic cases of SARS-CoV-2 infection in each arm,(Up to 2.5 months)
- Evaluation of the incidence of asymptomatic cases of SARS-CoV-2 infection in each arm(Up to 2.5 months)