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.
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.
Drug: Emtricitabine/tenofovir disoproxil
Emtricitabine/tenofovir disoproxil, 200 mg/245 mg tablets. A dose of one tablet once a day will be administered.
Drug: Hydroxychloroquine
Hydroxychloroquine, 200 mg tablets. A dose of one tablet once a day will be administered.
Drug: Placebo: Emtricitabine/tenofovir disoproxil Placebo
Placebo: Tablets similar in appearance to Emtricitabine/tenofovir disoproxil
Drug: Placebo: Hydroxychloroquine
Placebo: Tablets similar in appearance to Hydroxychloroquine
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
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
Hospital de Donostia
San Sebastián, Guipuzcoa, Spain
Hospital San Pedro
Logroño, La Rioja, Spain
Hospital Principe de Asturias
Alcalá De Henares, Madrid, Spain
Hospital Fundación de Alcorcón
Alcorcón, Madrid, Spain
Hospital Colllado Villalba
Collado-Villalba, Madrid, Spain
Hospital de Getafe
Getafe, Madrid, Spain
Hospital Severo Ochoa
Leganés, Madrid, Spain
Hospital de Móstoles
Móstoles, Madrid, Spain
Hospital Rey Juan Carlos
Móstoles, Madrid, Spain
Hospital Quirón Pozuelo
Pozuelo De Alarcón, Madrid, Spain
Hospital de Torrejón
Torrejón De Ardoz, 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
Tudela, Navarra, Spain
Hospital Arnau de Vilanova
Llíria, Valencia, Spain
Hospital de Araba
Alava, Vitoria, Spain
Hospital General Universitario de Albacete
Albacete, Spain
Centro Médico Teknon
Barcelona, Spain
Hospital Clinic
Barcelona, Spain
Hospital del Mar
Barcelona, Spain
Hospital Dexeus
Barcelona, Spain
Hospital Quirón Barcelona
Barcelona, Spain
Hospital Universitario Sagrat Cor
Barcelona, Spain
Hospital Universitario de Burgos
Burgos, 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
Fundación Jiménez Díaz
Madrid, Spain
Hospital Clinico San Carlos
Madrid, Spain
Hospital Infanta Leonor
Madrid, Spain
Hospital La Princesa
Madrid, Spain
Hospital Universitario 12 de Octubre
Madrid, Spain
Hospital Universitario Gregorio Marañon
Madrid, Spain
Hospital Universitario La Paz
Madrid, Spain
Hospital Universitario Puerta de Hierro
Madrid, Spain
Hospital Reina Sofía
Murcia, Spain
Hospital Universitario Virgen de la Arrixaca
Murcia, Spain
Hospital Virgen de la Victoria
Málaga, Spain
Complejo Asistencial de Palencia
Palencia, Spain
Hospital Universitario de Salamanca
Salamanca, Spain
Hospital General de Segovia
Segovia, Spain
Hospital Virgen del Rocio
Sevilla, Spain
Hospital Virgen Macarena
Sevilla, Spain
Hospital Clinico Universitario
Valencia, Spain
Hospital Dr. Peset
Valencia, Spain
Hospital General de Valencia
Valencia, Spain
Hospital La Fe
Valencia, Spain
Hospital de Valladolid
Valladolid, Spain
Hospital Rio Hortega
Valladolid, Spain
Hospital Lozano Blesa
Zaragoza, Spain
Hospital Miguel Servet
Zaragoza, Spain
Hospital Nuestra Señora de Sonsoles
Ávila, Spain