Clinical trial NCT04344379: Prevention of SARS-CoV-2 in Hospital Workers s Exposed to the Virus
Official title: Randomized Multicenter Study Evaluating the Efficacy of Azithromycin and Hydroxychloroquine in the Prevention of SARS-CoV-2 Infection in the Hospital Population Exposed to Virus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: SARS-CoV-2 Infection
Keywords: COVID-19
SARS-CoV-2
hydroxychloroquine
azithromycin
caregivers
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-04-14
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The Investigators propose to set up a preventive trial of infection in hospital workers at risk of coronavirus infection by comparing the rate of SARS-Cov-2 infection in a population of negative SARS-Cov-2 hospital workers receiving preventively azithromycin, hydroxychloroquine or a Placebo

Detailed description: Randomized clinical trial with 3 arms : hydroxychloroquine group, 300 subjects/azithromycin group, 300 subjects/ placebo of hydroxychloroquine group, 300 subjects. Hospital workers workers will be invited to participate in the study in each hospital and they will be included after giving their consent, assessment of their eligibility criteria, endonasal PCR and serolology at baseline. They will be randomized in one of the 3 arms, receive their treatment and will be followed by physical visit (at Day 2, Day 5, Day 15, Day 28) and by phone (at Day) 40 days with clinical data collection (tolerance and clinical signs of infection). At the end of treatment, another serology will be collected.

Eligibility criteria: Inclusion Criteria:

Hospital workers working at AP-HP hospitals over the age of 18

* Hospital workers who have signed consent
* No signs of COVID-19 infection
* Women who are likely to procreate should have a negative pregnancy test on inclusion day. In addition, they should use at least one effective contraceptive method before starting treatment, during treatment and up to 8 months after the last drug tested during the trial. Sexually active men should also have effective contraception during treatment and for at least 8 months after the last drug tested during the trial.
* Affiliated or beneficiary of Social Security

Exclusion Criteria:

* History of SARS-CoV-2 infection confirmed by PCR or serology is available at inclusion
* A history of clinical episode suspecting a PCR-confirmed or unconfirmed COVID-19 infection.
* Pregnancy and breastfeeding
* Allergy or contraindications to one of the 2 drugs in the study
* Known retinopathy
* Long congenital QT syndrome (or known in the family)
* QTc or 450 ms in men, or 460 ms in women, if Fc 55/mn (except in case of intense sport practice), if ESV on baseline ECG, if QRS - or 120 ms, if AC/FA, if the PR or BAV lengthening
* History of severe ischemic heart disease or unbalanced heart failure.
* Clinically significant bradycardia known
* Known kidney or liver failure
* Known G6PD deficit
* Subject who received antiviral treatment in the 14 days prior to inclusion
* Subject who had treatment with azithromycin or hydroxychloroquine, in the 14 days prior to inclusion
* Hypokaliemia (\<= 3.5 mmol/L), Increase in creatinine (\>=120 micromol/Ll, Increase in transaminases at baseline (\>=2N)

Primary outcomes:
measure: To assess the impact of hydroxychloroquine and azithromycin on the prevention of SARS-CoV-2 contamination in hospital workers exposed to 40 days of treatment.
timeFrame: 3 months
Secondary outcomes:
measure: Reducing clinical episodes due to suspected SARS-2 CoV infection confirmed by PCR
timeFrame: 40 days
measure: Reducing seroconversion for SARS-CoV-2 without any clinical sign
timeFrame: 3 months
measure: Evaluation of drug tolerance in the study
timeFrame: 40 days
measure: Evaluation on work stopping of hospital workers
timeFrame: 40 days
measure: Observance of treatment measured by plasmatic concentrations of hydroxychloroquine or azythromycine
timeFrame: 40 days
measure: Incidence of cardiologic events
timeFrame: 40 days
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Hopial Avicenne
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital GHU Paris Saclay
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Paris
country: France
facility: Hôpital Broca
city: Paris
country: France
facility: Hôpital La Pitié-Salpétrière
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital européen Georges Pompidou
city: Paris
country: France
facility: Hôpital Necker
Study officials:
affiliation: Assitance publique - Hôpitaux de Paris.
name: Jean Ma Treluyer, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: