Chemoprophylaxis of SARS-CoV-2 Infection (COVID-19) in Exposed Healthcare Workers (COVIDAXIS)

Centre Hospitalier Universitaire de Saint Etienne

Status and phase

Terminated

Phase 3

Conditions

COVID-19

Treatments

Drug: Placebo of LPV/r Tablets

Drug: Hydroxychloroquine

Drug: Lopinavir and ritonavir

Drug: Placebo of Hydroxychloroquine

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT04328285

20PH061

2020-001188-96 (EudraCT Number)

Details and patient eligibility

About

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:

Full 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

Enrollment

118 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

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

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

118 participants in 2 patient groups

Hydroxychloroquine (HCQ) vs Placebo

Experimental group

Description:

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.

Treatment: