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

Sponsor

Plan Nacional sobre el Sida (PNS) (Other)

Overall Status

Completed

CT.gov ID

NCT04334928

Collaborator

Effice Servicios Para la Investigacion S.L. (Industry)

1,002

Enrollment

Locations

Arms

14.9

Actual Duration (Months)

15.4

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Coronavirus Infection	Drug: Emtricitabine/tenofovir disoproxil Drug: Hydroxychloroquine Drug: Placebo: Emtricitabine/tenofovir disoproxil Placebo Drug: Placebo: Hydroxychloroquine	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

1002 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

Randomized double-blind clinical trial

Primary Purpose:

Prevention

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

Actual Study Start Date :

Apr 15, 2020

Actual Primary Completion Date :

Feb 25, 2021

Actual Study Completion Date :

Jul 11, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Number of confirmed symptomatic infections of SARS-CoV-2 (COVID-19) [12 weeks]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario de Ferrol	Ferrol	A Coruña	Spain
2	Hospital Clínico Universitario de Santiago	Santiago De Compostela	A Coruña	Spain
3	Hospital General de Elche	Elche	Alicante	Spain
4	Hospital Universitario Central de Asturias	Oviedo	Asturias	Spain
5	Hospital Sant Joan de Deu de Esplugues	Esplugues De Llobregat	Barcelona	Spain
6	Parc Sanitari Sant Joan de Déu de Sant Boi	Sant Boi De Llobregat	Barcelona	Spain
7	Hospital Moisès Broggi	Sant Joan Despí	Barcelona	Spain	08970
8	Hospital Infanta Margarita	Cabra	Córdoba	Spain
9	Hospital Insular de Las Palmas	Las Palmas De Gran Canaria	Gran Canaria	Spain
10	Hospital Universitario de Canarias	Las Palmas De Gran Canaria	Gran Canaria	Spain
11	Hospital de Donostia	San Sebastián	Guipuzcoa	Spain
12	Hospital San Pedro	Logroño	La Rioja	Spain
13	Hospital Principe de Asturias	Alcalá De Henares	Madrid	Spain
14	Hospital Fundación de Alcorcón	Alcorcón	Madrid	Spain
15	Hospital Colllado Villalba	Collado-Villalba	Madrid	Spain
16	Hospital de Getafe	Getafe	Madrid	Spain	28905
17	Hospital Severo Ochoa	Leganés	Madrid	Spain
18	Hospital de Móstoles	Móstoles	Madrid	Spain	28935
19	Hospital Rey Juan Carlos	Móstoles	Madrid	Spain
20	Hospital Quirón Pozuelo	Pozuelo De Alarcón	Madrid	Spain
21	Hospital de Torrejón	Torrejón De Ardoz	Madrid	Spain
22	Hospital Infanta Elena	Valdemoro	Madrid	Spain
23	Hospital Virgen del Castillo	Yecla	Murcia	Spain
24	Hospital Costa del Sol	Marbella	Málaga	Spain
25	Complejo Hospitalario de Navarra	Pamplona	Navarra	Spain
26	Hospital Reina Sofía	Tudela	Navarra	Spain	31500
27	Hospital Arnau de Vilanova	Llíria	Valencia	Spain
28	Hospital de Araba	Alava	Vitoria	Spain
29	Hospital General Universitario de Albacete	Albacete		Spain
30	Centro Médico Teknon	Barcelona		Spain
31	Hospital Clinic	Barcelona		Spain
32	Hospital del Mar	Barcelona		Spain
33	Hospital Dexeus	Barcelona		Spain
34	Hospital Quirón Barcelona	Barcelona		Spain
35	Hospital Universitario Sagrat Cor	Barcelona		Spain
36	Hospital Universitario de Burgos	Burgos		Spain
37	Hospital Virgen de la Luz	Cuenca		Spain
38	Hospital Clínico San Cecilio	Granada		Spain
39	Hospital Universitario de León	León		Spain
40	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
41	Fundación Jiménez Díaz	Madrid		Spain
42	Hospital Clinico San Carlos	Madrid		Spain
43	Hospital Infanta Leonor	Madrid		Spain
44	Hospital La Princesa	Madrid		Spain
45	Hospital Universitario 12 de Octubre	Madrid		Spain
46	Hospital Universitario Gregorio Marañon	Madrid		Spain
47	Hospital Universitario La Paz	Madrid		Spain
48	Hospital Universitario Puerta de Hierro	Madrid		Spain
49	Hospital Reina Sofía	Murcia		Spain
50	Hospital Universitario Virgen de la Arrixaca	Murcia		Spain
51	Hospital Virgen de la Victoria	Málaga		Spain
52	Complejo Asistencial de Palencia	Palencia		Spain
53	Hospital Universitario de Salamanca	Salamanca		Spain
54	Hospital General de Segovia	Segovia		Spain
55	Hospital Virgen del Rocio	Sevilla		Spain
56	Hospital Virgen Macarena	Sevilla		Spain
57	Hospital Clinico Universitario	Valencia		Spain
58	Hospital Dr. Peset	Valencia		Spain
59	Hospital General de Valencia	Valencia		Spain
60	Hospital La Fe	Valencia		Spain
61	Hospital de Valladolid	Valladolid		Spain
62	Hospital Rio Hortega	Valladolid		Spain
63	Hospital Lozano Blesa	Zaragoza		Spain
64	Hospital Miguel Servet	Zaragoza		Spain
65	Hospital Nuestra Señora de Sonsoles	Ávila		Spain