Chemoprophylaxis of SARS-CoV-2 Infection (COVID-19) in Exposed Healthcare Workers : A Randomized Double-blind Placebo-controlled Clinical Trial
Overview
- Phase
- Phase 3
- Intervention
- Hydroxychloroquine
- Conditions
- COVID-19
- Sponsor
- Centre Hospitalier Universitaire de Saint Etienne
- Enrollment
- 118
- Locations
- 9
- Primary Endpoint
- Occurrence of an symptomatic or asymptomatic SARS-CoV-2 infection among healthcare workers (HCWs)
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief Summary
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:
Detailed Description
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: * Group 2.1: LPV/r 200/50 mg : 2 tablets twice daily * Group 2.2: Placebo of LPV/r, 2 tablets twice daily Participants will receive the randomized treatment for 2 months and will be followed upon a 2.5 months period. NB: there is no randomization procedure for participant inclusion in either COVIDAXIS 1 or COVIDAXIS 2
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
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.
Intervention: Hydroxychloroquine
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.
Intervention: Placebo of Hydroxychloroquine
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
Intervention: Lopinavir and ritonavir
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
Intervention: Placebo of LPV/r Tablets
Outcomes
Primary Outcomes
Occurrence of an symptomatic or asymptomatic SARS-CoV-2 infection among healthcare workers (HCWs)
Time Frame: 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.
Secondary Outcomes
- 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)