## Protocol Section
### Identification Module
**NCT ID:** NCT04344379

**Acronym:** PREP-COVID

**Brief Title:** 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

#### Organization Study ID Info
**ID:** APHP200386
#### Organization
**Class:** OTHER
**Full Name:** Assistance Publique - Hôpitaux de Paris
#### Secondary ID Infos
**ID:** 2020-001273-73
**Type:** EUDRACT_NUMBER
### Status Module
#### Completion Date
**Date:** 2020-06-18

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2021-08-03

**Type:** ACTUAL

**Last Update Submit Date:** 2021-07-31

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2020-06-18

**Type:** ACTUAL

#### Start Date
**Date:** 2020-04-17

**Type:** ACTUAL

**Status Verified Date:** 2021-07

#### Study First Post Date
**Date:** 2020-04-14
**Type:** ACTUAL
**Study First Submit Date:** 2020-03-27
**Study First Submit QC Date:** 2020-04-10
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Assistance Publique - Hôpitaux de Paris

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- SARS-CoV-2 Infection

**Keywords:**

- COVID-19

- SARS-CoV-2

- hydroxychloroquine

- azithromycin

- caregivers

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** DOUBLE

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 122

**Type:** ACTUAL

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: hydroxychloroquine

**Label:** Arm Title : hydroxychloroquine

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Intervention Names:**

- Drug: hydroxychloroquine placebo

**Label:** Placebo of hydroxychloroquine

**Type:** PLACEBO_COMPARATOR

#### Arm Group 3

**Intervention Names:**

- Drug: azithromycin

**Label:** azythromycin

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Arm Title : hydroxychloroquine

**Description:** 200 mg BID per day

**Name:** hydroxychloroquine

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- azythromycin

**Description:** 250 mg per day

**Name:** azithromycin

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Placebo of hydroxychloroquine

**Description:** 200 mg BID per day

**Name:** hydroxychloroquine placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** The number of hospital workers with a positive serology or a positive PCR within 40 days of follow-up.

**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.

**Time Frame:** 3 months

#### Secondary Outcomes

**Description:** Clinical signs suggesting SARS-2 CoV infection confirmed by positive endonasal PCR

**Measure:** Reducing clinical episodes due to suspected SARS-2 CoV infection confirmed by PCR

**Time Frame:** 40 days

**Description:** number of seroconversion by serology between Day 0 and Day 40.

**Measure:** Reducing seroconversion for SARS-CoV-2 without any clinical sign

**Time Frame:** 3 months

**Description:** number of cardiological severe adverse events assessed (ECG abnormalities : widening QT, ventricular arythmia, and cardiac arrests), other serious adverse events including hospitalizations, and deaths

**Measure:** Evaluation of drug tolerance in the study

**Time Frame:** 40 days

**Description:** Number of work stoppages over the period

**Measure:** Evaluation on work stopping of hospital workers

**Time Frame:** 40 days

**Description:** Plasmatic concentrations of treatments

**Measure:** Observance of treatment measured by plasmatic concentrations of hydroxychloroquine or azythromycine

**Time Frame:** 40 days

**Description:** number of cardiac events, especialy ECG abnormalities (widening QT) due to treatments

**Measure:** Incidence of cardiologic events

**Time Frame:** 40 days

### Eligibility Module

**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)

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Bobigny

**Country:** France

**Facility:** Hopial Avicenne

**Zip:** 93000

**Location 2:**

**City:** Le Kremlin-Bicêtre

**Country:** France

**Facility:** Hôpital GHU Paris Saclay

**Zip:** 92100

**Location 3:**

**City:** Paris

**Country:** France

**Facility:** Hôpital Saint Antoine

**Zip:** 75012

**Location 4:**

**City:** Paris

**Country:** France

**Facility:** Hôpital Broca

**Zip:** 75013

**Location 5:**

**City:** Paris

**Country:** France

**Facility:** Hôpital La Pitié-Salpétrière

**Zip:** 75013

**Location 6:**

**City:** Paris

**Country:** France

**Facility:** Hôpital Cochin

**Zip:** 75014

**Location 7:**

**City:** Paris

**Country:** France

**Facility:** Hôpital européen Georges Pompidou

**Zip:** 75015

**Location 8:**

**City:** Paris

**Country:** France

**Facility:** Hôpital Necker

**Zip:** 75015

#### Overall Officials

**Official 1:**

**Affiliation:** Assitance publique - Hôpitaux de Paris.

**Name:** Jean Ma Treluyer, MD PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000011024

- Term: Pneumonia, Viral

- ID: D000011014

- Term: Pneumonia

- ID: D000012141

- Term: Respiratory Tract Infections

- ID: D000014777

- Term: Virus Diseases

- ID: D000018352

- Term: Coronavirus Infections

- ID: D000003333

- Term: Coronaviridae Infections

- ID: D000030341

- Term: Nidovirales Infections

- ID: D000012327

- Term: RNA Virus Infections

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M2561

- Name: COVID-19

- Relevance: HIGH

- As Found: SARS-CoV-2 Infection

- ID: M10283

- Name: Infections

- Relevance: HIGH

- As Found: Infection

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17522

- Name: Virus Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M13904

- Name: Pneumonia

- Relevance: LOW

- As Found: Unknown

- ID: M13914

- Name: Pneumonia, Viral

- Relevance: LOW

- As Found: Unknown

- ID: M14978

- Name: Respiratory Tract Infections

- Relevance: LOW

- As Found: Unknown

- ID: M20490

- Name: Coronavirus Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6555

- Name: Coronaviridae Infections

- Relevance: LOW

- As Found: Unknown

- ID: M23685

- Name: Nidovirales Infections

- Relevance: LOW

- As Found: Unknown

- ID: M15149

- Name: RNA Virus Infections

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000007239

- Term: Infections

- ID: D000086382

- Term: COVID-19

### Intervention Browse Module - Ancestors

- ID: D000000900

- Term: Anti-Bacterial Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000000962

- Term: Antimalarials

- ID: D000000981

- Term: Antiprotozoal Agents

- ID: D000000977

- Term: Antiparasitic Agents

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000018501

- Term: Antirheumatic Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: ARhu

- Name: Antirheumatic Agents

### Intervention Browse Module - Browse Leaves

- ID: M20132

- Name: Azithromycin

- Relevance: HIGH

- As Found: 20 minutes

- ID: M9940

- Name: Hydroxychloroquine

- Relevance: HIGH

- As Found: Bone marrow

- ID: M4222

- Name: Anti-Bacterial Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4280

- Name: Antimalarials

- Relevance: LOW

- As Found: Unknown

- ID: M4298

- Name: Antiprotozoal Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4294

- Name: Antiparasitic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M20604

- Name: Antirheumatic Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000017963

- Term: Azithromycin

- ID: D000006886

- Term: Hydroxychloroquine

### Misc Info Module

- Version Holder: 2024-05-24
