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

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

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.

Study Overview

• Status: Completed
• Conditions: Coronavirus Infection
• Intervention / Treatment: Drug: Emtricitabine/tenofovir disoproxil; Drug: Placebo: Hydroxychloroquine; Drug: Hydroxychloroquine; Drug: Placebo: Emtricitabine/tenofovir disoproxil Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 1002
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Albacete, Spain
    • Hospital General Universitario de Albacete
  • Barcelona, Spain
    • Hospital Del Mar
  • Barcelona, Spain
    • Hospital Clínic
  • Barcelona, Spain
    • Centro Médico Teknon
  • Barcelona, Spain
    • Hospital Dexeus
  • Barcelona, Spain
    • Hospital Quiron Barcelona
  • Barcelona, Spain
    • Hospital Universitario Sagrat Cor
  • Burgos, Spain
    • Hospital Universitario de Burgos
  • Cuenca, Spain
    • Hospital Virgen De La Luz
  • Granada, Spain
    • Hospital Clínico San Cecilio
  • León, Spain
    • Hospital Universitario de Leon
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain
    • Fundacion Jimenez Diaz
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Hospital La Princesa
  • Madrid, Spain
    • Hospital Infanta Leonor
  • Madrid, Spain
    • Hospital Universitario Puerta de Hierro
  • Madrid, Spain
    • Hospital Universitario Gregorio Marañon
  • Murcia, Spain
    • Hospital Universitario Virgen de la Arrixaca
  • Murcia, Spain
    • Hospital Reina Sofia
  • Málaga, Spain
    • Hospital Virgen de la Victoria
  • Palencia, Spain
    • Complejo Asistencial de Palencia
  • Salamanca, Spain
    • Hospital Universitario de Salamanca
  • Segovia, Spain
    • Hospital General de Segovia
  • Sevilla, Spain
    • Hospital Virgen del Rocío
  • Sevilla, Spain
    • Hospital Virgen Macarena
  • Valencia, Spain
    • Hospital General de Valencia
  • Valencia, Spain
    • Hospital La Fe
  • Valencia, Spain
    • Hospital Clinico Universitario
  • Valencia, Spain
    • Hospital Dr. Peset
  • Valladolid, Spain
    • Hospital Rio Hortega
  • Valladolid, Spain
    • Hospital de Valladolid
  • Zaragoza, Spain
    • Hospital Lozano Blesa
  • Zaragoza, Spain
    • Hospital Miguel Servet
  • Ávila, Spain
    • Hospital Nuestra Senora de Sonsoles
  • A Coruña
    • Ferrol, A Coruña, Spain
      • Hospital Universitario de Ferrol
    • Santiago De Compostela, A Coruña, Spain
      • Hospital Clinico Universitario de Santiago
  • Alicante
    • Elche, Alicante, Spain
      • Hospital General de Elche
  • Asturias
    • Oviedo, Asturias, Spain
      • Hospital Universitario Central de Asturias
  • Barcelona
    • Esplugues De Llobregat, Barcelona, Spain
      • Hospital Sant Joan de Deu de Esplugues
    • Sant Boi De Llobregat, Barcelona, Spain
      • Parc Sanitari Sant Joan de Déu de Sant Boi
    • Sant Joan Despí, Barcelona, Spain, 08970
      • Hospital Moisés Broggi
  • Córdoba
    • Cabra, Córdoba, Spain
      • Hospital Infanta Margarita
  • Gran Canaria
    • Las Palmas De Gran Canaria, Gran Canaria, Spain
      • Hospital Insular de las Palmas
    • Las Palmas De Gran Canaria, Gran Canaria, Spain
      • Hospital Universitario de Canarias
  • Guipuzcoa
    • San Sebastián, Guipuzcoa, Spain
      • Hospital de Donostia
  • La Rioja
    • Logroño, La Rioja, Spain
      • Hospital San Pedro
  • Madrid
    • Alcalá De Henares, Madrid, Spain
      • Hospital Principe de Asturias
    • Alcorcón, Madrid, Spain
      • Hospital Fundación de Alcorcón
    • Collado-Villalba, Madrid, Spain
      • Hospital Colllado Villalba
    • Getafe, Madrid, Spain, 28905
      • Hospital de Getafe
    • Leganés, Madrid, Spain
      • Hospital Severo Ochoa
    • Móstoles, Madrid, Spain, 28935
      • Hospital De Mostoles
    • Móstoles, Madrid, Spain
      • Hospital Rey Juan Carlos
    • Pozuelo De Alarcón, Madrid, Spain
      • Hospital Quirón Pozuelo
    • Torrejón De Ardoz, Madrid, Spain
      • Hospital de Torrejón
    • Valdemoro, Madrid, Spain
      • Hospital Infanta Elena
  • Murcia
    • Yecla, Murcia, Spain
      • Hospital Virgen del Castillo
  • Málaga
    • Marbella, Málaga, Spain
      • Hospital Costa del Sol
  • Navarra
    • Pamplona, Navarra, Spain
      • Complejo Hospitalario de Navarra
    • Tudela, Navarra, Spain, 31500
      • Hospital Reina Sofia
  • Valencia
    • Llíria, Valencia, Spain
      • Hospital Arnau de Vilanova
  • Vitoria
    • Alava, Vitoria, Spain
      • Hospital de Araba

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Emtricitabine/Tenofovir; 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)	Drug: Emtricitabine/tenofovir disoproxil; Emtricitabine/tenofovir disoproxil, 200 mg/245 mg tablets. A dose of one tablet once a day will be administered.; Drug: Placebo: Hydroxychloroquine; Placebo: Tablets similar in appearance to Hydroxychloroquine
Experimental: Hydroxychloroquine; 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)	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
Experimental: Emtricitabine/Tenofovir+Hydroxychloroquine; 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)	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.
Placebo Comparator: Placebo; 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)	Drug: Placebo: Hydroxychloroquine; Placebo: Tablets similar in appearance to Hydroxychloroquine; Drug: Placebo: Emtricitabine/tenofovir disoproxil Placebo; Placebo: Tablets similar in appearance to Emtricitabine/tenofovir disoproxil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of confirmed symptomatic infections of SARS-CoV-2 (COVID-19)	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Duration of symptoms in confirmed infected participants of SARS-CoV-2 (COVID-19) measured in days		12 weeks

Collaborators and Investigators

• Sponsor: Plan Nacional sobre el Sida (PNS)
• Collaborators: Effice Servicios Para la Investigacion S.L.
• Investigators: Study Chair: Rosa Polo, MD,PhD, Plan Nacional sobre el Sida (PNS); Study Chair: Miguel Hernán, MD,PhD, Harvard School of Public Health (HSPH)

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2020
• Primary Completion (Actual): February 25, 2021
• Study Completion (Actual): July 11, 2021

Study Registration Dates

• First Submitted: April 2, 2020
• First Submitted That Met QC Criteria: April 2, 2020
• First Posted (Actual): April 6, 2020

Study Record Updates

• Last Update Posted (Actual): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 15, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections; Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Hydroxychloroquine
• Other Study ID Numbers: PrEP COVID-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No