Clinical trial NCT04328285: Chemoprophylaxis of SARS-CoV-2 Infection (COVID-19) in Exposed Healthcare Workers
Official title: Chemoprophylaxis of SARS-CoV-2 Infection (COVID-19) in Exposed Healthcare Workers : A Randomized Double-blind Placebo-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: COVID-19
Keywords: SARS-CoV-2
COVID-19
nasopharyngeal swab
pneumonia
Hydroxychloroquine
Lopinavir/ritonavir
Healthcare Workers
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Institut Pasteur
First posted: 2020-03-31
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized double-blind placebo-controlled clinical trial
Primary purpose: PREVENTION

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

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
* 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

Primary outcomes:
measure: Occurrence of an symptomatic or asymptomatic SARS-CoV-2 infection among healthcare workers (HCWs)
timeFrame: Up to 2.5 months
Secondary outcomes:
measure: Evaluation of the occurrence of adverse events in each arm,
timeFrame: Up to 2.5 months
measure: Evaluation of the discontinuation rates of the investigational drug in each arm,
timeFrame: Up to 2 months
measure: Evaluation of the adherence of participants to study drug,
timeFrame: Up to 2 months
measure: Evaluation of the incidence of symptomatic cases of SARS-CoV-2 infection in each arm,
timeFrame: Up to 2.5 months
measure: Evaluation of the incidence of asymptomatic cases of SARS-CoV-2 infection in each arm
timeFrame: Up to 2.5 months
measure: Evaluation of the incidence of severe cases of SARS-CoV-2 infection in each arm.
timeFrame: Up to 2.5 months
measure: corrected QT interval (ms)
timeFrame: At baseline, at D2 (only for COVIDAXIS 1) and every week up to 2 months.
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU d'Angers
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Clermont-ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nancy
country: France
facility: CHU de Nancy
city: Nantes
country: France
facility: CHU de Nantes
city: Rennes
country: France
facility: CHU de Rennes
city: Rouen
country: France
facility: CHU de Rouen
city: Saint-Étienne
country: France
facility: CHU de Saint-Etienne
Study officials:
affiliation: CHU de Saint-Etienne
name: Elisabeth Botelho-Nevers, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Pasteur
name: Bruno Hoen, MD, PhD
role: STUDY_DIRECTOR
References: