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

NCT ID: NCT04334928

Last Updated: 2021-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1002 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-15
• Study Completion Date: 2021-07-11

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.

Conditions

Coronavirus Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Emtricitabine/Tenofovir

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)

Group Type: EXPERIMENTAL

Emtricitabine/tenofovir disoproxil

Intervention Type: DRUG

Emtricitabine/tenofovir disoproxil, 200 mg/245 mg tablets. A dose of one tablet once a day will be administered.

Placebo: Hydroxychloroquine

Intervention Type: DRUG

Placebo: Tablets similar in appearance to 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)

Group Type: EXPERIMENTAL

Hydroxychloroquine

Intervention Type: DRUG

Hydroxychloroquine, 200 mg tablets. A dose of one tablet once a day will be administered.

Placebo: Emtricitabine/tenofovir disoproxil Placebo

Intervention Type: DRUG

Placebo: Tablets similar in appearance to Emtricitabine/tenofovir disoproxil

Emtricitabine/Tenofovir+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)

Group Type: EXPERIMENTAL

Emtricitabine/tenofovir disoproxil

Intervention Type: DRUG

Emtricitabine/tenofovir disoproxil, 200 mg/245 mg tablets. A dose of one tablet once a day will be administered.

Hydroxychloroquine

Intervention Type: DRUG

Hydroxychloroquine, 200 mg tablets. A dose of one tablet once a day will be administered.

Placebo

Placebo of Tenofovir Disoproxil Fumarate 245 mg/Emtricitabine 200 mg + Placebo of Hydroxychloroquine 200 mg

1. Placebo tablets with similar appearance to study drugs.

2. Dose: one tablet once a day (both at dinner)

Group Type: PLACEBO_COMPARATOR

Placebo: Emtricitabine/tenofovir disoproxil Placebo

Intervention Type: DRUG

Placebo: Tablets similar in appearance to Emtricitabine/tenofovir disoproxil

Placebo: Hydroxychloroquine

Intervention Type: DRUG

Placebo: Tablets similar in appearance to Hydroxychloroquine

Interventions

Emtricitabine/tenofovir disoproxil

Emtricitabine/tenofovir disoproxil, 200 mg/245 mg tablets. A dose of one tablet once a day will be administered.

Intervention Type: DRUG

Hydroxychloroquine

Hydroxychloroquine, 200 mg tablets. A dose of one tablet once a day will be administered.

Intervention Type: DRUG

Placebo: Emtricitabine/tenofovir disoproxil Placebo

Placebo: Tablets similar in appearance to Emtricitabine/tenofovir disoproxil

Intervention Type: DRUG

Placebo: Hydroxychloroquine

Placebo: Tablets similar in appearance to Hydroxychloroquine

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Effice Servicios Para la Investigacion S.L.

INDUSTRY

Sponsor Role: collaborator

Plan Nacional sobre el Sida (PNS)

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rosa Polo, MD,PhD

Role: STUDY_CHAIR

Plan Nacional sobre el Sida (PNS)

Miguel Hernán, MD,PhD

Role: STUDY_CHAIR

Harvard School of Public Health (HSPH)

Locations

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 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, Navarre, Spain

Hospital Reina Sofía

Tudela, Navarre, Spain

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, Spain

Hospital Arnau de Vilanova

Llíria, Valencia, Spain

Hospital de Araba

Alava, Vitoria, Spain

Hospital General Universitario de Albacete

Albacete, , Spain

Hospital Nuestra Señora de Sonsoles

Ávila, , 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 Virgen de la Victoria

Málaga, , Spain

Hospital Reina Sofía

Murcia, , Spain

Hospital Universitario Virgen de la Arrixaca

Murcia, , Spain

Complejo Asistencial de Palencia

Palencia, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Hospital General de Segovia

Segovia, , Spain

Hospital Virgen del Rocio

Seville, , Spain

Hospital Virgen Macarena

Seville, , 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

Countries

Spain

Other Identifiers

PrEP COVID-19

Identifier Type: -

Identifier Source: org_study_id