Pre-Exposure Prophylaxis With Hydroxychloroquine for High-Risk Healthcare Workers During the COVID-19 Pandemic (PrEP_COVID)

Pre-Exposure Prophylaxis With Hydroxychloroquine for High-Risk Healthcare Workers During the COVID-19 Pandemic: A Multicentre, Double-Blinded Randomized Controlled Trial

The investigators aim to evaluate the efficacy of pre-exposure prophylaxis with hydroxychloroquine in healthcare workers with high-risk of SARS-CoV-2 infection.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Hydroxychloroquine; Drug: Placebos

• Study Type: Interventional
• Enrollment (Actual): 275
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • ISGlobal

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years
• Negative PCR and negative serology on day 0
• Healthcare worker at any of the trial sites
• Female participants: negative for pregnancy test
• Willing to participate in the study
• Able to sign the informed consent form

Exclusion Criteria:

• Age <18 years
• Pregnancy or breastfeeding
• Ongoing antiviral or antiretroviral treatment or HIV positive
• Ongoing anti-inflammatory treatment (corticosteroids)
• Ongoing or previous (1 month) chloroquine or hydroxychloroquine treatment
• Confirmed case of SARS-CoV-2 infection (positive PCR) at day 0
• Positive serology for SARS-CoV-1 infection at day 0
• Impossibility of signing the informed consent form
• Rejection of participation
• Working less than 3 days a week in the Hospital Clinic of Barcelona.

• Any contraindication for hydroxychloroquine treatment:

  • Hydroxychloroquine hypersensitivity or 4-aminoquinoline hypersensitivity
  • Retinopathy, visual field or visual acuity disturbances
  • QT prolongation, bradycardia (<50bpm), ventricular tachycardia, other arrhythmias, as determined on day 0 ECG or medical history
  • Potassium < 3 mEq/L or AST or ALT > 5 upper normal limit, as determined on day 0 blood test
  • Previous myocardial infarction
  • Myasthenia gravis
  • Porphyria
  • Glomerular clearance < 10ml/min
  • Previous history of severe hypoglycaemia
  • Ongoing treatment with antimalarials, antiarrhythmic, tricyclic antidepressants, selective serotonin reuptake inhibitors, natalizumab, quinolones, macrolides, agalsidase alfa and beta.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pre-exposure prophylaxis of SARS-CoV-2; Participants will receive hydroxychloroquine 400 mg daily during the first 4 days, followed by 400 mg weekly during 6 months	Drug: Hydroxychloroquine; Hydroxychloroquine with the following dosage: day 0: 400 mg (2 tablets); day 1: 400 mg (2 tablets); day 2: 400 mg (2 tablets); day 3: 400 mg (2 tablets); weekly: 400 mg (2 tablets) for a period of six months
Placebo Comparator: Control group with placebo; Participants will receive placebo 400 mg daily during the first 4 days, followed by 400 mg weekly during 6 months	Drug: Placebos; Placebo with the following dosage: day 0: 400 mg (2 tablets); day 1: 400 mg (2 tablets); day 2: 400 mg (2 tablets); day 3: 400 mg (2 tablets); weekly: 400 mg (2 tablets) for a period of six months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed cases of a COVID-19	Confirmed cases of a COVID-19 (defined by a positive PCR for SARS-CoV-2 or symptoms compatible with COVID-19 with seroconversion) in the PrEP group compared to the placebo group at any time during the 6 months of the follow-up in healthcare workers with negative PCR for SARS-CoV-2 on day 0 and negative serology for SARS-CoV-2 on day 0.	Up to 6 months after start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SARS-CoV-2 seroconversion	SARS-CoV-2 seroconversion in the PrEP group compared to placebo in during 6 months of follow-up in healthcare workers with negative serology at day 0.	Up to 6 months after start of treatment
Occurrence of any adverse event related with hydroxychloroquine treatment	Incidence of clinical and/or laboratory adverse events will be compared in the PrEP group and in the placebo arm.	Up to 6 months after start of treatment
Incidence of SARS-CoV-2 infection and COVID-19 among healthcare workers	Incidence of SARS-CoV-2 infection and COVID-19 among healthcare workers will be estimated by the number of healthcare workers diagnosed with COVID-19 in the placebo group, among the total of healthcare workers included in the non-PrEP group during the study period.	Up to 6 months after start of treatment
Risk ratio for the different clinical, analytical and microbiological conditions to develop COVID-19		Up to 6 months after start of treatment
COVID-19 Biobank	A repository (biobank) of serum samples obtained from healthcare workers confirmed COVID-19 cases for future research on blood markers to predict SARS-CoV-2 infection.	Up to 6 months after start of treatment

Collaborators and Investigators

• Sponsor: Barcelona Institute for Global Health
• Collaborators: Hospital Clinic of Barcelona; Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau; Hospital de Granollers; Hospital Plató; Laboratorios Rubió

Publications and helpful links

General Publications

• Grau-Pujol B, Camprubi-Ferrer D, Marti-Soler H, Fernandez-Pardos M, Carreras-Abad C, Andres MV, Ferrer E, Muelas-Fernandez M, Jullien S, Barilaro G, Ajanovic S, Vera I, Moreno L, Gonzalez-Redondo E, Cortes-Serra N, Roldan M, Arcos AA, Mur I, Domingo P, Garcia F, Guinovart C, Munoz J. Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: a double-blind, placebo-controlled randomized clinical trial. Trials. 2021 Nov 15;22(1):808. doi: 10.1186/s13063-021-05758-9.
• Grau-Pujol B, Camprubi D, Marti-Soler H, Fernandez-Pardos M, Guinovart C, Munoz J. Pre-exposure prophylaxis with hydroxychloroquine for high-risk healthcare workers during the COVID-19 pandemic: A structured summary of a study protocol for a multicentre, double-blind randomized controlled trial. Trials. 2020 Jul 29;21(1):688. doi: 10.1186/s13063-020-04621-7.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2020
• Primary Completion (Actual): June 25, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: April 1, 2020
• First Submitted That Met QC Criteria: April 1, 2020
• First Posted (Actual): April 2, 2020

Study Record Updates

• Last Update Posted (Actual): May 1, 2023
• Last Update Submitted That Met QC Criteria: April 28, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: PrEP; prophylaxis; hydroxychloroquine; healthcare workers; pre-exposure
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: PrEP_COVID

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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