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

Coronavirus Infection Clinical Trial

— EPICOS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04334928
• Other study ID #: PrEP COVID-19
• Status: Completed
• Phase: Phase 3
• Start date: April 15, 2020
• Est. completion date: July 11, 2021

Study information

• Verified date: September 2021
• Source: Plan Nacional sobre el Sida (PNS)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1002
• Est. completion date: July 11, 2021
• Est. primary completion date: February 25, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Coronavirus Infection
• Coronavirus Infections
• COVID-19
• Infections

Intervention

Drug:
• Emtricitabine/tenofovir disoproxil
Emtricitabine/tenofovir disoproxil, 200 mg/245 mg tablets. A dose of one tablet once a day will be administered.
• Hydroxychloroquine
Hydroxychloroquine, 200 mg tablets. A dose of one tablet once a day will be administered.
• Placebo: Emtricitabine/tenofovir disoproxil Placebo
Placebo: Tablets similar in appearance to Emtricitabine/tenofovir disoproxil
• Placebo: Hydroxychloroquine
Placebo: Tablets similar in appearance to Hydroxychloroquine

Locations

Country	Name	City	State
Spain	Hospital de Araba	Alava	Vitoria
Spain	Hospital General Universitario de Albacete	Albacete
Spain	Hospital Principe de Asturias	Alcalá De Henares	Madrid
Spain	Hospital Fundación de Alcorcón	Alcorcón	Madrid
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 Infanta Margarita	Cabra	Córdoba
Spain	Hospital Colllado Villalba	Collado-Villalba	Madrid
Spain	Hospital Virgen de la Luz	Cuenca
Spain	Hospital General de Elche	Elche	Alicante
Spain	Hospital Sant Joan de Deu de Esplugues	Esplugues De Llobregat	Barcelona
Spain	Hospital Universitario de Ferrol	Ferrol	A Coruña
Spain	Hospital de Getafe	Getafe	Madrid
Spain	Hospital Clínico San Cecilio	Granada
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 Severo Ochoa	Leganés	Madrid
Spain	Hospital Universitario de León	León
Spain	Hospital Arnau de Vilanova	Llíria	Valencia
Spain	Hospital San Pedro	Logroño	La Rioja
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 Universitario Ramón y Cajal	Madrid
Spain	Hospital Virgen de la Victoria	Málaga
Spain	Hospital Costa del Sol	Marbella	Málaga
Spain	Hospital de Móstoles	Móstoles	Madrid
Spain	Hospital Rey Juan Carlos	Móstoles	Madrid
Spain	Hospital Reina Sofía	Murcia
Spain	Hospital Universitario Virgen de la Arrixaca	Murcia
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturias
Spain	Complejo Asistencial de Palencia	Palencia
Spain	Complejo Hospitalario de Navarra	Pamplona	Navarra
Spain	Hospital Quirón Pozuelo	Pozuelo De Alarcón	Madrid
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital de Donostia	San Sebastián	Guipuzcoa
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 Clínico Universitario de Santiago	Santiago De Compostela	A Coruña
Spain	Hospital General de Segovia	Segovia
Spain	Hospital Virgen del Rocio	Sevilla
Spain	Hospital Virgen Macarena	Sevilla
Spain	Hospital de Torrejón	Torrejón De Ardoz	Madrid
Spain	Hospital Reina Sofía	Tudela	Navarra
Spain	Hospital Infanta Elena	Valdemoro	Madrid
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 Virgen del Castillo	Yecla	Murcia
Spain	Hospital Lozano Blesa	Zaragoza
Spain	Hospital Miguel Servet	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
Plan Nacional sobre el Sida (PNS)	Effice Servicios Para la Investigacion S.L.

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of confirmed symptomatic infections of SARS-CoV-2 (COVID-19)		12 weeks
Secondary	Severity of disease in confirmed infected participants of SARS-CoV-2 (COVID-19)	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	12 weeks
Secondary	Duration of symptoms in confirmed infected participants of SARS-CoV-2 (COVID-19) measured in days		12 weeks