Clinical trial NCT04304053: Treatment of COVID-19 Cases and Chemoprophylaxis of Contacts as Prevention
Official title: Treatment of Non-severe Confirmed Cases of COVID-19 and Chemoprophylaxis of Their Contacts as Prevention Strategy: a Cluster Randomized Clinical Trial (PEP CoV-2 Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Lead sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Sponsor class: OTHER
Collaborators: name: Germans Trias i Pujol Hospital
name: Department of Health, Generalitat de Catalunya
name: Laboratorios Gebro Pharma SA
name: Laboratorios Rubió
name: Institut Catala de Salut
First posted: 2020-03-11
Enrollment: 2300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Primary study: Cluster-randomized clinical trial of Covid-19 contacts

Secondary study: Randomized clinical trial of Covid-19 cases
Primary purpose: PREVENTION

Brief summary: This study is a research project to evaluate the efficacy of hydroxychloroquine for post-exposure prophylaxis and early treatment of Covid-19. The intervention entails administering prophylactic hydroxychloroquine to all contacts (Study 1) and treating non severe confirmed cases with hydroxychloroquine (Study 2).

Detailed description: Hydroxychloroquine (HCQ) is a drug that has been extensively used for the prevention of malaria. HCQ showed excellent in vitro results and strong antiviral effects on SARS-CoV-2 infection of primate cells at low concentration. Empirical data for the efficacy of HCQ in hospitalized Covid-19 patients became available after the start of this study; HCQ administration did not result in a significantly higher PCR negative conversion in a RCT including 150 patients and there was no reduction in the risk of death/intubation in two large observational studies.

Study 1 -We investigated the efficacy and safety of HCQ to prevent secondary SARS-CoV-2 infection and Covid-19 disease in contacts exposed to a PCR-positive Covid-19 case during.

Study 2- We also conducted a study to test the hypothesis that HCQ treatment would be more efficacious than no-treatment for patients with mild Covid-19.

Initially, the protocol included the use of combined treatment with a HIV protease inhibidor (cobicistat-boosted darunavir) for cases (study 2), but it was adapted to HCQ alone after the recommendation of the pharmaceutical company not to use DRVc for the treatment of Covid-19 due to lack of activity in-vitro.

Eligibility criteria: Study 1:

Inclusion Criteria for a contact:

1. Asymptomatic individuals exposed to a PCR confirmed COVID19 case within 7 days as either a healthcare worker or household contact
2. Aged ≥18 years male or female;
3. In women of childbearing potential, negative pregnancy test and commitment to use contraceptive method throughout the study.
4. Willing to take study medication;
5. Willing to comply with all study procedures;
6. Able to provide oral, informed consent and/or assent.

Exclusion Criteria for a contact:

1. With known history of cardiac arrhythmia (or QT prolongation syndrome);
2. Unable to take drugs by mouth;
3. With significantly abnormal liver function (Child Pugh C)
4. Need of dialysis treatment, or GFR≤30 mL/min/1.73 m2;
5. Participants with psoriasis, myasthenia, haematopoietic and retinal diseases,CNS-related hearing loss or glucose-6-phosphate dehydrogenase deficit;
6. Persons already treated with any of the study drugs during the last 30 days;
7. Pregnant or lactating women;
8. Any contraindications as per the Data Sheet of Hydroxychloroquine.

Study 2:

Inclusion Criteria for a case:

1. Patients who meet the requirements of the New Coronavirus Infection Diagnosis (Acute \<5 days respiratory infection symptoms, or fever alone, or acute cough alone and positive PCR)
2. Aged ≥18 years male or female;
3. In women of childbearing potential, negative pregnancy test and commitment to use contraceptive method throughout the study.
4. Willing to take study medication
5. Willing to comply with all study procedures, including repeat nasal swab at day 3
6. Able to provide oral and written informed consent

Exclusion Criteria for a case:

1. Hospital admission
2. Serious condition meeting one of the following: (1) respiratory distress with respiratory rate \>=30 breaths/min; (2) oxygen saturation\<=93% on quiet status; (3) Arterial partial pressure of oxygen (PaO2)/oxygen concentration\<=300mmHg;
3. Critically ill patients meeting one of the following: (1) Experience respiratory failure and need to receive mechanical ventilation; (2) Experience shock; (3) Complicated with other organs failure and need intensive care and therapy in ICU;
4. Participants under treatment with medications likely to interfere with experimental drugs
5. Unable to take drugs by mouth;
6. With significantly abnormal liver function (Child Pugh C)
7. Need of dialysis treatment, or GFR≤30 mL/min/1.73 m2;
8. Participants with psoriasis, myasthenia, haematopoietic and retinal diseases,CNS-related hearing loss or glucose-6-phosphate dehydrogenase deficit
9. Participants with severe neurological and mental illness;
10. Pregnant or lactating women;
11. Inability to consent and/or comply with study protocol;
12. Individuals with known hypersensitivity to the study drugs.
13. Persons already treated with any of the study drugs during the last 30 days.
14. Any contraindications as per the Data Sheet of Hydroxychloroquine.

Primary outcomes:
measure: Study 1- Clinical and virological outcome in exposed contacts
timeFrame: Up to 14 days after start of treatment
measure: Study 1- Transmission of SARS-CoV-2 in exposed contacts
timeFrame: Up to 14 days after start of treatment
measure: Study 2- Virological outcome in index cases
timeFrame: Up to 7 days after start of treatment
measure: Study 2- Clinical outcome in index cases
timeFrame: Up to 28 days after start of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Departament de Salut
Study officials:
References:
citation: Akhtar S, Das JK, Ismail T, Wahid M, Saeed W, Bhutta ZA. Nutritional perspectives for the prevention and mitigation of COVID-19. Nutr Rev. 2021 Feb 11;79(3):289-300. doi: 10.1093/nutrit/nuaa063.
citation: Mitja O, Corbacho-Monne M, Ubals M, Alemany A, Suner C, Tebe C, Tobias A, Penafiel J, Ballana E, Perez CA, Admella P, Riera-Marti N, Laporte P, Mitja J, Clua M, Bertran L, Sarquella M, Gavilan S, Ara J, Argimon JM, Cuatrecasas G, Canadas P, Elizalde-Torrent A, Fabregat R, Farre M, Forcada A, Flores-Mateo G, Lopez C, Muntada E, Nadal N, Narejos S, Nieto A, Prat N, Puig J, Quinones C, Ramirez-Viaplana F, Reyes-Uruena J, Riveira-Munoz E, Ruiz L, Sanz S, Sentis A, Sierra A, Velasco C, Vivanco-Hidalgo RM, Zamora J, Casabona J, Vall-Mayans M, Gonzalez-Beiras C, Clotet B; BCN-PEP-CoV2 Research Group. A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19. N Engl J Med. 2021 Feb 4;384(5):417-427. doi: 10.1056/NEJMoa2021801. Epub 2020 Nov 24.