Clinical trial NCT04334928: Randomized Clinical Trial for the Prevention of SARS-CoV-2 Infection (COVID-19) in Healthcare Personnel
Official title: Prevention of SARS-CoV-2 (COVID-19) Through Pre-Exposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine and Hydroxychloroquine in Healthcare Personnel: Randomized Clinical Trial Controlled With Placebo
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Coronavirus Infection
Keywords: COVID-19
SARS-CoV-2
Lead sponsor: Plan Nacional sobre el Sida (PNS)
Sponsor class: OTHER_GOV
Collaborators: name: Effice Servicios Para la Investigacion S.L.
First posted: 2020-04-06
Enrollment: 1002
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of confirmed symptomatic infections of SARS-CoV-2 (COVID-19)
timeFrame: 12 weeks
Secondary outcomes:
measure: Severity of disease in confirmed infected participants of SARS-CoV-2 (COVID-19)
timeFrame: 12 weeks
measure: Duration of symptoms in confirmed infected participants of SARS-CoV-2 (COVID-19) measured in days
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Ferrol
country: Spain
facility: Hospital Universitario de Ferrol
state: A Coruña
city: Santiago De Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago
state: A Coruña
city: Elche
country: Spain
facility: Hospital General de Elche
state: Alicante
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Esplugues De Llobregat
country: Spain
facility: Hospital Sant Joan de Deu de Esplugues
state: Barcelona
city: Sant Boi De Llobregat
country: Spain
facility: Parc Sanitari Sant Joan de Déu de Sant Boi
state: Barcelona
city: Sant Joan Despí
country: Spain
facility: Hospital Moisès Broggi
state: Barcelona
city: Cabra
country: Spain
facility: Hospital Infanta Margarita
state: Córdoba
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Insular de Las Palmas
state: Gran Canaria
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario de Canarias
state: Gran Canaria
city: San Sebastián
country: Spain
facility: Hospital de Donostia
state: Guipuzcoa
city: Logroño
country: Spain
facility: Hospital San Pedro
state: La Rioja
city: Alcalá De Henares
country: Spain
facility: Hospital Principe de Asturias
state: Madrid
city: Alcorcón
country: Spain
facility: Hospital Fundación de Alcorcón
state: Madrid
city: Collado-Villalba
country: Spain
facility: Hospital Colllado Villalba
state: Madrid
city: Getafe
country: Spain
facility: Hospital de Getafe
state: Madrid
city: Leganés
country: Spain
facility: Hospital Severo Ochoa
state: Madrid
city: Móstoles
country: Spain
facility: Hospital de Móstoles
state: Madrid
city: Móstoles
country: Spain
facility: Hospital Rey Juan Carlos
state: Madrid
city: Pozuelo De Alarcón
country: Spain
facility: Hospital Quirón Pozuelo
state: Madrid
city: Torrejón De Ardoz
country: Spain
facility: Hospital de Torrejón
state: Madrid
city: Valdemoro
country: Spain
facility: Hospital Infanta Elena
state: Madrid
city: Yecla
country: Spain
facility: Hospital Virgen del Castillo
state: Murcia
city: Marbella
country: Spain
facility: Hospital Costa del Sol
state: Málaga
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: Navarra
city: Tudela
country: Spain
facility: Hospital Reina Sofía
state: Navarra
city: Llíria
country: Spain
facility: Hospital Arnau de Vilanova
state: Valencia
city: Alava
country: Spain
facility: Hospital de Araba
state: Vitoria
city: Albacete
country: Spain
facility: Hospital General Universitario de Albacete
city: Barcelona
country: Spain
facility: Centro Médico Teknon
city: Barcelona
country: Spain
facility: Hospital Clinic
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Dexeus
city: Barcelona
country: Spain
facility: Hospital Quirón Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitario Sagrat Cor
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos
city: Cuenca
country: Spain
facility: Hospital Virgen de la Luz
city: Granada
country: Spain
facility: Hospital Clínico San Cecilio
city: León
country: Spain
facility: Hospital Universitario de León
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Infanta Leonor
city: Madrid
country: Spain
facility: Hospital La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Murcia
country: Spain
facility: Hospital Reina Sofía
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Málaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Palencia
country: Spain
facility: Complejo Asistencial de Palencia
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Segovia
country: Spain
facility: Hospital General de Segovia
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Clinico Universitario
city: Valencia
country: Spain
facility: Hospital Dr. Peset
city: Valencia
country: Spain
facility: Hospital General de Valencia
city: Valencia
country: Spain
facility: Hospital La Fe
city: Valladolid
country: Spain
facility: Hospital de Valladolid
city: Valladolid
country: Spain
facility: Hospital Rio Hortega
city: Zaragoza
country: Spain
facility: Hospital Lozano Blesa
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
city: Ávila
country: Spain
facility: Hospital Nuestra Señora de Sonsoles
Study officials:
affiliation: Plan Nacional sobre el Sida (PNS)
name: Rosa Polo, MD,PhD
role: STUDY_CHAIR
affiliation: Harvard School of Public Health (HSPH)
name: Miguel Hernán, MD,PhD
role: STUDY_CHAIR
References: