Randomized Clinical Trial for the Prevention of SARS-CoV-2 Infection (COVID-19) in Healthcare Personnel
- Conditions
- Coronavirus Infection
- Interventions
- Drug: Emtricitabine/tenofovir disoproxil
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1002
- 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.
- 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 Central de Asturias
🇪🇸Oviedo, Asturias, Spain
Hospital Rey Juan Carlos
🇪🇸Móstoles, Madrid, Spain
Hospital de Torrejón
🇪🇸Torrejón De Ardoz, Madrid, Spain
Hospital Arnau de Vilanova
🇪🇸Llíria, Valencia, Spain
Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Hospital Clínico Universitario de Santiago
🇪🇸Santiago De Compostela, A Coruña, Spain
Hospital Universitario de Ferrol
🇪🇸Ferrol, A Coruña, Spain
Hospital General de Elche
🇪🇸Elche, Alicante, Spain
Hospital Sant Joan de Deu de Esplugues
🇪🇸Esplugues De Llobregat, Barcelona, Spain
Hospital Infanta Margarita
🇪🇸Cabra, Córdoba, Spain
Hospital Moisès Broggi
🇪🇸Sant Joan Despí, Barcelona, Spain
Hospital Insular de Las Palmas
🇪🇸Las Palmas De Gran Canaria, Gran Canaria, Spain
Hospital de Donostia
🇪🇸San Sebastián, Guipuzcoa, Spain
Hospital Universitario de Canarias
🇪🇸Las Palmas De Gran Canaria, Gran Canaria, Spain
Hospital San Pedro
🇪🇸Logroño, La Rioja, Spain
Hospital Colllado Villalba
🇪🇸Collado-Villalba, Madrid, Spain
Hospital Principe de Asturias
🇪🇸Alcalá De Henares, Madrid, Spain
Hospital Fundación de Alcorcón
🇪🇸Alcorcón, Madrid, Spain
Hospital Quirón Pozuelo
🇪🇸Pozuelo De Alarcón, Madrid, Spain
Hospital Severo Ochoa
🇪🇸Leganés, Madrid, Spain
Hospital de Getafe
🇪🇸Getafe, Madrid, Spain
Hospital de Móstoles
🇪🇸Móstoles, Madrid, Spain
Hospital Infanta Elena
🇪🇸Valdemoro, Madrid, Spain
Hospital Virgen del Castillo
🇪🇸Yecla, Murcia, Spain
Hospital Costa del Sol
🇪🇸Marbella, Málaga, Spain
Complejo Hospitalario de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Reina Sofía
🇪🇸Murcia, Spain
Hospital General Universitario de Albacete
🇪🇸Albacete, Spain
Hospital de Araba
🇪🇸Alava, Vitoria, Spain
Centro Médico Teknon
🇪🇸Barcelona, Spain
Hospital Clinic
🇪🇸Barcelona, Spain
Hospital Dexeus
🇪🇸Barcelona, Spain
Hospital Universitario Sagrat Cor
🇪🇸Barcelona, Spain
Hospital Universitario de Burgos
🇪🇸Burgos, Spain
Hospital Quirón Barcelona
🇪🇸Barcelona, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Virgen de la Luz
🇪🇸Cuenca, Spain
Hospital Clínico San Cecilio
🇪🇸Granada, Spain
Hospital Universitario de León
🇪🇸León, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Infanta Leonor
🇪🇸Madrid, Spain
Hospital Virgen de la Victoria
🇪🇸Málaga, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital La Princesa
🇪🇸Madrid, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Madrid, Spain
Hospital Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
Complejo Asistencial de Palencia
🇪🇸Palencia, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital General de Segovia
🇪🇸Segovia, Spain
Hospital Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Clinico Universitario
🇪🇸Valencia, Spain
Hospital Dr. Peset
🇪🇸Valencia, Spain
Hospital La Fe
🇪🇸Valencia, Spain
Hospital General de Valencia
🇪🇸Valencia, Spain
Hospital de Valladolid
🇪🇸Valladolid, Spain
Hospital Lozano Blesa
🇪🇸Zaragoza, Spain
Hospital Rio Hortega
🇪🇸Valladolid, Spain
Hospital Nuestra Señora de Sonsoles
🇪🇸Ávila, Spain
Hospital Miguel Servet
🇪🇸Zaragoza, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Parc Sanitari Sant Joan de Déu de Sant Boi
🇪🇸Sant Boi De Llobregat, Barcelona, Spain