Randomized Clinical Trial for the Prevention of SARS-CoV-2 Infection (COVID-19) in Healthcare Personnel

Phase 3

Completed

• Conditions: Coronavirus Infection
• Interventions: Drug: Emtricitabine/tenofovir disoproxil; Drug: Hydroxychloroquine

• Registration Number: NCT04334928
• Lead Sponsor: Plan Nacional sobre el Sida (PNS)

Brief Summary

Healthcare workers are particularly at risk of SARS-CoV-2. This study aims to assess the efficacy of a daily single dose of tenofovir disoproxil fumarate (TDF) (245 mg)/ Emtricitabine (FTC) (200 mg), a daily single dose of hydroxychloroquine (HC) (200 mg), a daily single dose of TDF (245 mg)/FTC (200 mg) plus HC (200 mg) versus placebo, during 12 weeks in: (1) reducing the incidence of symptomatic disease and (2) reducing clinical severity COVID-19 among hospital healthcare workers aged 18 to 70 years in public and private hospitals in Spain.

Detailed Description

Healthcare workers are particularly at risk of SARS-CoV-2. In the absence of a vaccine, other strategies aiming to reduce the development of COVID-19 in the population, more specifically in healthcare workers is being sought. Administration of effective drugs to people at risk of developing an infectious disease is well accepted and is part of clinical practice. To date there are few on-going randomized clinical trial on Pre-exposure prophylaxis (PrEP) evaluating chloroquine and hydroxychloroquine efficacy for health care workers and other groups at high risk. Existing recent and scarce literature shows that RNA synthesis nucleos(t)ide analogue inhibitors, acting as viral RNA chain terminators, like TDF, abacavir or lamivudine, amongst others, could have an effect against SARS-CoV-2 infection. Worldwide, there is broad evidence of the use, safety and tolerability of hydroxychloroquine (200 mg) and TDF/FTC (245 mg/200 mg). This study aims to assess the efficacy of a daily single dose of TDF (245 mg)/FTC (200 mg), a daily single dose of HC (200 mg), a daily single dose of TDF (245 mg)/FTC (200 mg) plus HC (200 mg) versus placebo, during 12 weeks in: (1) reducing the incidence of symptomatic disease and (2) reducing clinical severity COVID-19 among hospital healthcare workers aged 18 to 70 years in public and private hospitals in Spain. Sample size calculations are based on the primary outcome; number of symptomatic confirmed infections by SARS-CoV-2. Briefly, 4.000 participants will be assigned to one of the 4 groups, through 1:1:1:1 randomization. Duration of prophylactic treatment will be 12 weeks from early April 2020 till early July 2020. Follow up of participants will continue up to 4 weeks after last dose of treatment. All participants will be assessed on a monthly basis. Interim analyses will be performed on monthly bases.

Study Timeline

• Study First Submitted: 2020-04-02
• Study First Submitted QC: 2020-04-02
• Study First Posted: 2020-04-06
• Study Start: 2020-04-15
• Primary Completion: 2021-02-25
• Study Completion: 2021-07-11
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-15
• Last Update Posted: 2021-09-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1002

Inclusion Criteria

• Participants that, after receiving appropriate information on the study design, objectives, possible risks and acknowledging they have the right to withdraw from the study consent at any time, sing the informed consent for participation in the study.
• Male or female aged 18-70years.
• Health care workers in public or private hospitals in areas of risk of SARS-CoV-2 transmission.
• No previous diagnosis of SARS-CoV-2 (COVID-19) infection plus no symptoms compatible with SARS-CoV-2 (COVID-19) since 1st of March 2020 until the date of enrolment in the study.
• Understanding of the aim of the study and, therefore, acknowledging they have not been on any drug aiming at pre exposure prophylaxis against SARS-CoV-2 (COVID-19) since 1st of March 2020. This also includes PrEP for HIV.
• Negative pregnancy test during the previous 7 days to start treatments or more than 2 years after menopause.
• Women of reproductive age and their partners should commit to use and highly effective contraceptive method ( double barrier, hormonal contraception), during the study period and until 6 months after the last dose of treatment.

Exclusion Criteria

• Having symptoms suggestive of COVID-19 infection
• HIV infection
• Active hepatitis B infection.
• Renal failure with estimated glomerular filtration rate (GFR) < 60 ml/min) and patients on Hemodialysis.
• Osteoporosis
• Myasthenia gravis
• Pre-existent maculopathy.
• Retinitis pigmentosa
• Bradycardia < 50bpm
• Weight < 40kg
• Participant with any immunosuppressive condition or hematological disease.
• Have taken any medications such as PrEP against SARS-CoV-2 from March 1, 2020 until trial entry (also includes PrEP for HIV).
• Treatment with drugs that may prolong QT in the last month before randomization for more than 7 days including: azithromycin, chlorpromazine, cisapride, clarithromycin, domperidone, droperidol, erythromycin, halofantrine, haloperidol, lumefantrine, mefloquine, methadone, pentamidine, procainamide, quinidine, quinine, sotalol, sparfloxacin, thioridazine, amiodarone.
• Breastfeeding
• Known allergy to any of the medication used in this trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Emtricitabine/Tenofovir+Hydroxychloroquine	Emtricitabine/tenofovir disoproxil	Tenofovir Disoproxil Fumarate 245 mg/Emtricitabine 200 mg + Hydroxychloroquine 200 mg 1. Strength FTC/TDF:200 mg/245 mg tablets 2. Strength HC: 200 mg tablets 3. Dose: one tablet FTC/TDF plus one tablet HC once a day (at dinner)
Emtricitabine/Tenofovir	Emtricitabine/tenofovir disoproxil	Tenofovir Disoproxil Fumarate 245 mg/Emtricitabine 200 mg + Placebo of Hydroxychloroquine 200 mg 1. Strength: 200 mg/245 mg tablets 2. Dose: one tablet once a day (both at dinner)
Hydroxychloroquine	Hydroxychloroquine	Hydroxychloroquine 200 mg + Placebo of Tenofovir Disoproxil Fumarate 245 mg/Emtricitabine 200 mg 1. Strength: 200 mg tablets 2. Dose: one tablet once a day (both at dinner)
Emtricitabine/Tenofovir+Hydroxychloroquine	Hydroxychloroquine	Tenofovir Disoproxil Fumarate 245 mg/Emtricitabine 200 mg + Hydroxychloroquine 200 mg 1. Strength FTC/TDF:200 mg/245 mg tablets 2. Strength HC: 200 mg tablets 3. Dose: one tablet FTC/TDF plus one tablet HC once a day (at dinner)

Primary Outcome Measures

Name	Time	Method
Number of confirmed symptomatic infections of SARS-CoV-2 (COVID-19)	12 weeks

Secondary Outcome Measures

Name	Time	Method
Duration of symptoms in confirmed infected participants of SARS-CoV-2 (COVID-19) measured in days	12 weeks
Severity of disease in confirmed infected participants of SARS-CoV-2 (COVID-19)	12 weeks	assessed by: * No symptoms; * Mild symptoms: general malaise, fever, cough, myalgia, asthenia.; * Moderate symptoms: mild symptoms plus shortness of breath,; * Severe symptoms: mild symptoms plus respiratory insufficiency that requires admission in intensive care unit and mechanical ventilation

Trial Locations

Locations (64)

Hospital Universitario de Ferrol; 🇪🇸 Ferrol, A Coruña, Spain

Hospital Clínico Universitario de Santiago; 🇪🇸 Santiago De Compostela, A Coruña, Spain

Hospital General de Elche; 🇪🇸 Elche, Alicante, Spain

Hospital Universitario Central de Asturias; 🇪🇸 Oviedo, Asturias, Spain

Hospital Sant Joan de Deu de Esplugues; 🇪🇸 Esplugues De Llobregat, Barcelona, Spain

Parc Sanitari Sant Joan de Déu de Sant Boi; 🇪🇸 Sant Boi De Llobregat, Barcelona, Spain

Hospital Moisès Broggi; 🇪🇸 Sant Joan Despí, Barcelona, Spain

Hospital Infanta Margarita; 🇪🇸 Cabra, Córdoba, Spain

Hospital Insular de Las Palmas; 🇪🇸 Las Palmas De Gran Canaria, Gran Canaria, Spain

Hospital Universitario de Canarias; 🇪🇸 Las Palmas De Gran Canaria, Gran Canaria, Spain

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