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

• ClinicalTrials.gov Identifier: NCT04331834
• Recruitment Status: Completed
• First Posted: April 2, 2020
• Last Update Posted: February 16, 2021
• Sponsor: Barcelona Institute for Global Health
• Collaborators: Hospital Clinic of Barcelona; Laboratorios Rubió; Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau; Hospital Plató; Hospital de Granollers
• Information provided by (Responsible Party): Barcelona Institute for Global Health

Tracking Information

• First Submitted Date: April 1, 2020
• First Posted Date: April 2, 2020
• Last Update Posted Date: February 16, 2021
• Actual Study Start Date: April 3, 2020
• Actual Primary Completion Date: June 25, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 13, 2020)

Confirmed cases of a COVID-19 [ Time Frame: Up to 6 months after start of treatment ]

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.

Original Primary Outcome Measures (submitted: April 1, 2020)

Confirmed cases of a COVID-19 [ Time Frame: Up to 6 months after start of treatment ]

Confirmed cases of a COVID-19 (defined by symptoms compatible with COVID-19 and/or a positive PCR for SARS-CoV-2) 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 at day 0.

Current Secondary Outcome Measures (submitted: April 1, 2020)

• SARS-CoV-2 seroconversion [ Time Frame: Up to 6 months after start of treatment ]
  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.
• Occurrence of any adverse event related with hydroxychloroquine treatment [ Time Frame: Up to 6 months after start of treatment ]
  Incidence of clinical and/or laboratory adverse events will be compared in the PrEP group and in the placebo arm.
• Incidence of SARS-CoV-2 infection and COVID-19 among healthcare workers [ Time Frame: Up to 6 months after start of treatment ]
  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.
• Risk ratio for the different clinical, analytical and microbiological conditions to develop COVID-19 [ Time Frame: Up to 6 months after start of treatment ]
• COVID-19 Biobank [ Time Frame: Up to 6 months after start of treatment ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pre-Exposure Prophylaxis With Hydroxychloroquine for High-Risk Healthcare Workers During the COVID-19 Pandemic
• Official Title: Pre-Exposure Prophylaxis With Hydroxychloroquine for High-Risk Healthcare Workers During the COVID-19 Pandemic: A Multicentre, Double-Blinded Randomized Controlled Trial
• Brief Summary: The investigators aim to evaluate the efficacy of pre-exposure prophylaxis with hydroxychloroquine in healthcare workers with high-risk of SARS-CoV-2 infection.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: COVID-19

Intervention

• 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
• 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

Study Arms

• 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
  Intervention: Drug: Hydroxychloroquine
• 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
  Intervention: Drug: Placebos

• Publications *: Grau-Pujol B, Camprubí D, Marti-Soler H, Fernández-Pardos M, Guinovart C, Muñoz 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 15, 2021): 275
• Original Estimated Enrollment (submitted: April 1, 2020): 440
• Actual Study Completion Date: December 31, 2020
• Actual Primary Completion Date: June 25, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT04331834
• Other Study ID Numbers: PrEP_COVID
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Barcelona Institute for Global Health
• Study Sponsor: Barcelona Institute for Global Health

Collaborators

• Hospital Clinic of Barcelona
• Laboratorios Rubió
• Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Hospital Plató
• Hospital de Granollers

Investigators

• Principal Investigator: Jose Muñoz Gutiérrez, MD, PhD; Barcelona Institute for Global Health

• PRS Account: Barcelona Institute for Global Health
• Verification Date: April 2020