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

• ClinicalTrials.gov Identifier: NCT04334928
• Recruitment Status: Completed
• First Posted: April 6, 2020
• Last Update Posted: September 16, 2021
• Sponsor: Plan Nacional sobre el Sida (PNS)
• Collaborator: Effice Servicios Para la Investigacion S.L.
• Information provided by (Responsible Party): Plan Nacional sobre el Sida (PNS)

Tracking Information

• First Submitted Date: April 2, 2020
• First Posted Date: April 6, 2020
• Last Update Posted Date: September 16, 2021
• Actual Study Start Date: April 15, 2020
• Actual Primary Completion Date: February 25, 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 2, 2020): Number of confirmed symptomatic infections of SARS-CoV-2 (COVID-19) [ Time Frame: 12 weeks ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 2, 2020)

• Severity of disease in confirmed infected participants of SARS-CoV-2 (COVID-19) [ Time Frame: 12 weeks ]
  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 [ Time Frame: 12 weeks ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Randomized double-blind clinical trial

Primary Purpose: Prevention

• Condition: Coronavirus Infection

Intervention

• 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.
• Drug: Placebo: Emtricitabine/tenofovir disoproxil Placebo
  Placebo: Tablets similar in appearance to Emtricitabine/tenofovir disoproxil
• Drug: Placebo: Hydroxychloroquine
  Placebo: Tablets similar in appearance to Hydroxychloroquine

Study Arms

• Experimental: 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)
  Interventions:

  • Drug: Emtricitabine/tenofovir disoproxil
  • Drug: Placebo: Hydroxychloroquine
• Experimental: 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)
  Interventions:

  • Drug: Hydroxychloroquine
  • Drug: Placebo: Emtricitabine/tenofovir disoproxil Placebo
• Experimental: 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)
  Interventions:

  • Drug: Emtricitabine/tenofovir disoproxil
  • Drug: Hydroxychloroquine
• Placebo Comparator: 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)
  Interventions:

  • Drug: Placebo: Emtricitabine/tenofovir disoproxil Placebo
  • Drug: Placebo: Hydroxychloroquine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 16, 2021): 1002
• Original Estimated Enrollment (submitted: April 2, 2020): 4000
• Actual Study Completion Date: July 11, 2021
• Actual Primary Completion Date: February 25, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT04334928
• Other Study ID Numbers: PrEP COVID-19
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Plan Nacional sobre el Sida (PNS)
• Original Responsible Party: Same as current
• Current Study Sponsor: Plan Nacional sobre el Sida (PNS)
• Original Study Sponsor: Same as current
• 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)

• PRS Account: Plan Nacional sobre el Sida (PNS)
• Verification Date: September 2021