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

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

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

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pre-exposure prophylaxis of SARS-CoV-2<br>Participants will receive hydroxychloroquine 400 mg daily during the first 4 days, followed by 400 mg weekly during 6 months | Drug: Hydroxychloroquine<br>* 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<br>|
| Placebo Comparator: Control group with placebo<br>Participants will receive placebo 400 mg daily during the first 4 days, followed by 400 mg weekly during 6 months | Drug: Placebos<br>* 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<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prophylaxis, PrEP, hydroxychloroquine, pre-exposure, healthcare workers