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

Primary Purpose

Coronavirus Infection

Status
Completed
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Emtricitabine/tenofovir disoproxil
Hydroxychloroquine
Placebo: Emtricitabine/tenofovir disoproxil Placebo
Placebo: Hydroxychloroquine
Sponsored by
Plan Nacional sobre el Sida (PNS)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Coronavirus Infection focused on measuring COVID-19, SARS-CoV-2

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Hospital Universitario de Ferrol
  • Hospital Clínico Universitario de Santiago
  • Hospital General de Elche
  • Hospital Universitario Central de Asturias
  • Hospital Sant Joan de Deu de Esplugues
  • Parc Sanitari Sant Joan de Déu de Sant Boi
  • Hospital Moisès Broggi
  • Hospital Infanta Margarita
  • Hospital Insular de Las Palmas
  • Hospital Universitario de Canarias
  • Hospital de Donostia
  • Hospital San Pedro
  • Hospital Principe de Asturias
  • Hospital Fundación de Alcorcón
  • Hospital Colllado Villalba
  • Hospital de Getafe
  • Hospital Severo Ochoa
  • Hospital de Móstoles
  • Hospital Rey Juan Carlos
  • Hospital Quirón Pozuelo
  • Hospital de Torrejón
  • Hospital Infanta Elena
  • Hospital Virgen del Castillo
  • Hospital Costa del Sol
  • Complejo Hospitalario de Navarra
  • Hospital Reina Sofía
  • Hospital Arnau de Vilanova
  • Hospital de Araba
  • Hospital General Universitario de Albacete
  • Centro Médico Teknon
  • Hospital Clinic
  • Hospital del Mar
  • Hospital Dexeus
  • Hospital Quirón Barcelona
  • Hospital Universitario Sagrat Cor
  • Hospital Universitario de Burgos
  • Hospital Virgen de la Luz
  • Hospital Clínico San Cecilio
  • Hospital Universitario de León
  • Hospital Universitario Ramón y Cajal
  • Fundación Jiménez Díaz
  • Hospital Clinico San Carlos
  • Hospital Infanta Leonor
  • Hospital La Princesa
  • Hospital Universitario 12 de Octubre
  • Hospital Universitario Gregorio Marañon
  • Hospital Universitario La Paz
  • Hospital Universitario Puerta de Hierro
  • Hospital Reina Sofía
  • Hospital Universitario Virgen de la Arrixaca
  • Hospital Virgen de la Victoria
  • Complejo Asistencial de Palencia
  • Hospital Universitario de Salamanca
  • Hospital General de Segovia
  • Hospital Virgen del Rocio
  • Hospital Virgen Macarena
  • Hospital Clinico Universitario
  • Hospital Dr. Peset
  • Hospital General de Valencia
  • Hospital La Fe
  • Hospital de Valladolid
  • Hospital Rio Hortega
  • Hospital Lozano Blesa
  • Hospital Miguel Servet
  • Hospital Nuestra Señora de Sonsoles

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Emtricitabine/Tenofovir

Hydroxychloroquine

Emtricitabine/Tenofovir+Hydroxychloroquine

Placebo

Arm Description

Tenofovir Disoproxil Fumarate 245 mg/Emtricitabine 200 mg + Placebo of Hydroxychloroquine 200 mg Strength: 200 mg/245 mg tablets Dose: one tablet once a day (both at dinner)

Hydroxychloroquine 200 mg + Placebo of Tenofovir Disoproxil Fumarate 245 mg/Emtricitabine 200 mg Strength: 200 mg tablets Dose: one tablet once a day (both at dinner)

Tenofovir Disoproxil Fumarate 245 mg/Emtricitabine 200 mg + Hydroxychloroquine 200 mg Strength FTC/TDF:200 mg/245 mg tablets Strength HC: 200 mg tablets Dose: one tablet FTC/TDF plus one tablet HC once a day (at dinner)

Placebo of Tenofovir Disoproxil Fumarate 245 mg/Emtricitabine 200 mg + Placebo of Hydroxychloroquine 200 mg Placebo tablets with similar appearance to study drugs. Dose: one tablet once a day (both at dinner)

Outcomes

Primary Outcome Measures

Number of confirmed symptomatic infections of SARS-CoV-2 (COVID-19)

Secondary Outcome Measures

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
Duration of symptoms in confirmed infected participants of SARS-CoV-2 (COVID-19) measured in days

Full Information

First Posted
April 2, 2020
Last Updated
September 15, 2021
Sponsor
Plan Nacional sobre el Sida (PNS)
Collaborators
Effice Servicios Para la Investigacion S.L.
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1. Study Identification

Unique Protocol Identification Number
NCT04334928
Brief Title
Randomized Clinical Trial for the Prevention of SARS-CoV-2 Infection (COVID-19) in Healthcare Personnel
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
April 15, 2020 (Actual)
Primary Completion Date
February 25, 2021 (Actual)
Study Completion Date
July 11, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Plan Nacional sobre el Sida (PNS)
Collaborators
Effice Servicios Para la Investigacion S.L.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronavirus Infection
Keywords
COVID-19, SARS-CoV-2

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Randomized double-blind clinical trial
Allocation
Randomized
Enrollment
1002 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Emtricitabine/Tenofovir
Arm Type
Experimental
Arm Description
Tenofovir Disoproxil Fumarate 245 mg/Emtricitabine 200 mg + Placebo of Hydroxychloroquine 200 mg Strength: 200 mg/245 mg tablets Dose: one tablet once a day (both at dinner)
Arm Title
Hydroxychloroquine
Arm Type
Experimental
Arm Description
Hydroxychloroquine 200 mg + Placebo of Tenofovir Disoproxil Fumarate 245 mg/Emtricitabine 200 mg Strength: 200 mg tablets Dose: one tablet once a day (both at dinner)
Arm Title
Emtricitabine/Tenofovir+Hydroxychloroquine
Arm Type
Experimental
Arm Description
Tenofovir Disoproxil Fumarate 245 mg/Emtricitabine 200 mg + Hydroxychloroquine 200 mg Strength FTC/TDF:200 mg/245 mg tablets Strength HC: 200 mg tablets Dose: one tablet FTC/TDF plus one tablet HC once a day (at dinner)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo of Tenofovir Disoproxil Fumarate 245 mg/Emtricitabine 200 mg + Placebo of Hydroxychloroquine 200 mg Placebo tablets with similar appearance to study drugs. Dose: one tablet once a day (both at dinner)
Intervention Type
Drug
Intervention Name(s)
Emtricitabine/tenofovir disoproxil
Intervention Description
Emtricitabine/tenofovir disoproxil, 200 mg/245 mg tablets. A dose of one tablet once a day will be administered.
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Intervention Description
Hydroxychloroquine, 200 mg tablets. A dose of one tablet once a day will be administered.
Intervention Type
Drug
Intervention Name(s)
Placebo: Emtricitabine/tenofovir disoproxil Placebo
Intervention Description
Placebo: Tablets similar in appearance to Emtricitabine/tenofovir disoproxil
Intervention Type
Drug
Intervention Name(s)
Placebo: Hydroxychloroquine
Intervention Description
Placebo: Tablets similar in appearance to Hydroxychloroquine
Primary Outcome Measure Information:
Title
Number of confirmed symptomatic infections of SARS-CoV-2 (COVID-19)
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Severity of disease in confirmed infected participants of SARS-CoV-2 (COVID-19)
Description
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
Time Frame
12 weeks
Title
Duration of symptoms in confirmed infected participants of SARS-CoV-2 (COVID-19) measured in days
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rosa Polo, MD,PhD
Organizational Affiliation
Plan Nacional sobre el Sida (PNS)
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Miguel Hernán, MD,PhD
Organizational Affiliation
Harvard School of Public Health (HSPH)
Official's Role
Study Chair
Facility Information:
Facility Name
Hospital Universitario de Ferrol
City
Ferrol
State/Province
A Coruña
Country
Spain
Facility Name
Hospital Clínico Universitario de Santiago
City
Santiago De Compostela
State/Province
A Coruña
Country
Spain
Facility Name
Hospital General de Elche
City
Elche
State/Province
Alicante
Country
Spain
Facility Name
Hospital Universitario Central de Asturias
City
Oviedo
State/Province
Asturias
Country
Spain
Facility Name
Hospital Sant Joan de Deu de Esplugues
City
Esplugues De Llobregat
State/Province
Barcelona
Country
Spain
Facility Name
Parc Sanitari Sant Joan de Déu de Sant Boi
City
Sant Boi De Llobregat
State/Province
Barcelona
Country
Spain
Facility Name
Hospital Moisès Broggi
City
Sant Joan Despí
State/Province
Barcelona
ZIP/Postal Code
08970
Country
Spain
Facility Name
Hospital Infanta Margarita
City
Cabra
State/Province
Córdoba
Country
Spain
Facility Name
Hospital Insular de Las Palmas
City
Las Palmas De Gran Canaria
State/Province
Gran Canaria
Country
Spain
Facility Name
Hospital Universitario de Canarias
City
Las Palmas De Gran Canaria
State/Province
Gran Canaria
Country
Spain
Facility Name
Hospital de Donostia
City
San Sebastián
State/Province
Guipuzcoa
Country
Spain
Facility Name
Hospital San Pedro
City
Logroño
State/Province
La Rioja
Country
Spain
Facility Name
Hospital Principe de Asturias
City
Alcalá De Henares
State/Province
Madrid
Country
Spain
Facility Name
Hospital Fundación de Alcorcón
City
Alcorcón
State/Province
Madrid
Country
Spain
Facility Name
Hospital Colllado Villalba
City
Collado-Villalba
State/Province
Madrid
Country
Spain
Facility Name
Hospital de Getafe
City
Getafe
State/Province
Madrid
ZIP/Postal Code
28905
Country
Spain
Facility Name
Hospital Severo Ochoa
City
Leganés
State/Province
Madrid
Country
Spain
Facility Name
Hospital de Móstoles
City
Móstoles
State/Province
Madrid
ZIP/Postal Code
28935
Country
Spain
Facility Name
Hospital Rey Juan Carlos
City
Móstoles
State/Province
Madrid
Country
Spain
Facility Name
Hospital Quirón Pozuelo
City
Pozuelo De Alarcón
State/Province
Madrid
Country
Spain
Facility Name
Hospital de Torrejón
City
Torrejón De Ardoz
State/Province
Madrid
Country
Spain
Facility Name
Hospital Infanta Elena
City
Valdemoro
State/Province
Madrid
Country
Spain
Facility Name
Hospital Virgen del Castillo
City
Yecla
State/Province
Murcia
Country
Spain
Facility Name
Hospital Costa del Sol
City
Marbella
State/Province
Málaga
Country
Spain
Facility Name
Complejo Hospitalario de Navarra
City
Pamplona
State/Province
Navarra
Country
Spain
Facility Name
Hospital Reina Sofía
City
Tudela
State/Province
Navarra
ZIP/Postal Code
31500
Country
Spain
Facility Name
Hospital Arnau de Vilanova
City
Llíria
State/Province
Valencia
Country
Spain
Facility Name
Hospital de Araba
City
Alava
State/Province
Vitoria
Country
Spain
Facility Name
Hospital General Universitario de Albacete
City
Albacete
Country
Spain
Facility Name
Centro Médico Teknon
City
Barcelona
Country
Spain
Facility Name
Hospital Clinic
City
Barcelona
Country
Spain
Facility Name
Hospital del Mar
City
Barcelona
Country
Spain
Facility Name
Hospital Dexeus
City
Barcelona
Country
Spain
Facility Name
Hospital Quirón Barcelona
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario Sagrat Cor
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario de Burgos
City
Burgos
Country
Spain
Facility Name
Hospital Virgen de la Luz
City
Cuenca
Country
Spain
Facility Name
Hospital Clínico San Cecilio
City
Granada
Country
Spain
Facility Name
Hospital Universitario de León
City
León
Country
Spain
Facility Name
Hospital Universitario Ramón y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Fundación Jiménez Díaz
City
Madrid
Country
Spain
Facility Name
Hospital Clinico San Carlos
City
Madrid
Country
Spain
Facility Name
Hospital Infanta Leonor
City
Madrid
Country
Spain
Facility Name
Hospital La Princesa
City
Madrid
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Gregorio Marañon
City
Madrid
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Puerta de Hierro
City
Madrid
Country
Spain
Facility Name
Hospital Reina Sofía
City
Murcia
Country
Spain
Facility Name
Hospital Universitario Virgen de la Arrixaca
City
Murcia
Country
Spain
Facility Name
Hospital Virgen de la Victoria
City
Málaga
Country
Spain
Facility Name
Complejo Asistencial de Palencia
City
Palencia
Country
Spain
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
Country
Spain
Facility Name
Hospital General de Segovia
City
Segovia
Country
Spain
Facility Name
Hospital Virgen del Rocio
City
Sevilla
Country
Spain
Facility Name
Hospital Virgen Macarena
City
Sevilla
Country
Spain
Facility Name
Hospital Clinico Universitario
City
Valencia
Country
Spain
Facility Name
Hospital Dr. Peset
City
Valencia
Country
Spain
Facility Name
Hospital General de Valencia
City
Valencia
Country
Spain
Facility Name
Hospital La Fe
City
Valencia
Country
Spain
Facility Name
Hospital de Valladolid
City
Valladolid
Country
Spain
Facility Name
Hospital Rio Hortega
City
Valladolid
Country
Spain
Facility Name
Hospital Lozano Blesa
City
Zaragoza
Country
Spain
Facility Name
Hospital Miguel Servet
City
Zaragoza
Country
Spain
Facility Name
Hospital Nuestra Señora de Sonsoles
City
Ávila
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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