Prevention of SARS-CoV-2 in Hospital Workers s Exposed to the Virus (PREP-COVID)

• ClinicalTrials.gov Identifier: NCT04344379
• Recruitment Status: Completed
• First Posted: April 14, 2020
• Last Update Posted: August 3, 2021
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

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

Condition or disease	Intervention/treatment	Phase
SARS-CoV-2 Infection	Drug: hydroxychloroquine; Drug: azithromycin; Drug: hydroxychloroquine placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 122 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: April 17, 2020
• Actual Primary Completion Date: June 18, 2020
• Actual Study Completion Date: June 18, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm Title : hydroxychloroquine	Drug: hydroxychloroquine; 200 mg BID per day
Placebo Comparator: Placebo of hydroxychloroquine	Drug: hydroxychloroquine placebo; 200 mg BID per day
Active Comparator: azythromycin	Drug: azithromycin; 250 mg per day

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: 3 months ]
   The number of hospital workers with a positive serology or a positive PCR within 40 days of follow-up.

Secondary Outcome Measures :

1. Reducing clinical episodes due to suspected SARS-2 CoV infection confirmed by PCR [ Time Frame: 40 days ]
   Clinical signs suggesting SARS-2 CoV infection confirmed by positive endonasal PCR
2. Reducing seroconversion for SARS-CoV-2 without any clinical sign [ Time Frame: 3 months ]
   number of seroconversion by serology between Day 0 and Day 40.
3. Evaluation of drug tolerance in the study [ Time Frame: 40 days ]
   number of cardiological severe adverse events assessed (ECG abnormalities : widening QT, ventricular arythmia, and cardiac arrests), other serious adverse events including hospitalizations, and deaths
4. Evaluation on work stopping of hospital workers [ Time Frame: 40 days ]
   Number of work stoppages over the period
5. Observance of treatment measured by plasmatic concentrations of hydroxychloroquine or azythromycine [ Time Frame: 40 days ]
   Plasmatic concentrations of treatments
6. Incidence of cardiologic events [ Time Frame: 40 days ]
   number of cardiac events, especialy ECG abnormalities (widening QT) due to treatments

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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)

Contacts and Locations

Locations

France

Hopial Avicenne

Bobigny, France, 93000

Hôpital GHU Paris Saclay

Le Kremlin-Bicêtre, France, 92100

Hôpital Saint Antoine

Paris, France, 75012

Hôpital Broca

Paris, France, 75013

Hôpital La Pitié-Salpétrière

Paris, France, 75013

Hôpital Cochin

Paris, France, 75014

Hôpital européen Georges Pompidou

Paris, France, 75015

Hôpital Necker

Paris, France, 75015

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

• Principal Investigator: Jean Ma Treluyer, MD PhD; Assitance publique - Hôpitaux de Paris.

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT04344379
• Other Study ID Numbers: APHP200386; 2020-001273-73 ( EudraCT Number )
• First Posted: April 14, 2020
• Last Update Posted: August 3, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:

COVID-19; SARS-CoV-2; hydroxychloroquine; azithromycin; caregivers

Additional relevant MeSH terms:

COVID-19; Infections; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Azithromycin; Hydroxychloroquine; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents