Treatment of COVID-19 Cases and Chemoprophylaxis of Contacts as Prevention (HCQ4COV19)

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)

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).

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Other: Standard Public Health measures; Drug: Treatment and prophylaxis

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.

• Study Type: Interventional
• Enrollment (Actual): 2300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
    • Departament de Salut

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: No Intervention- SARS-CoV-2 surveillance; Study 1- Contacts will complete a survey collecting demographic, epidemiological and clinical data and provides a swab for RT-PCR testing at baseline and day 14. Study 2- Index case completes a survey collecting demographic, epidemiological and clinical data and provides a swab for RT-PCR testing at baseline and on days 3 and 7. Isolation of patient and contact tracing as per national guidelines.	Other: Standard Public Health measures; Isolation of patient and contact tracing as per national guidelines.
Experimental: Testing, treatment and prophylaxis of SARS-CoV-2; Study 1- Contacts receive Hydroxychloroquine prophylaxis. Contacts will complete a survey collecting demographic, epidemiological and clinical and provides a swab for RT-PCR testing at baseline and day 14. Study 2- Index case receives Hydroxychloroquine. Index case completes a survey collecting demographic, epidemiological and clinical data and provides a swab for RT-PCR testing at baseline and on days 3, and 7. Isolation of patient and contact tracing as per national guidelines.	Other: Standard Public Health measures; Isolation of patient and contact tracing as per national guidelines.; Drug: Treatment and prophylaxis; Cases will be offered a therapeutic regimen hydroxychloroquine (200mg tablets) 800mg on day 1, and 400mg on days 2-7 Contacts will be offered a prophylactic regimen of hydroxychloroquine (200mg tablets) 800mg on day 1, and 400mg on days 2-7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study 1- Clinical and virological outcome in exposed contacts	Incidence of secondary PCR confirmed symptomatic Covid-19 episodes among contacts after high risk PCR+ exposure	Up to 14 days after start of treatment
Study 1- Transmission of SARS-CoV-2 in exposed contacts	Incidence of symptomatically compatible or a PCR-positive result regardless of symptoms	Up to 14 days after start of treatment
Study 2- Virological outcome in index cases	Reduction of viral RNA load in nasopharyngeal swabs at days 3, and 7 after treatment start.	Up to 7 days after start of treatment
Study 2- Clinical outcome in index cases	Time from randomization to complete resolution of symptoms at an extended 28-days follow-	Up to 28 days after start of treatment

Collaborators and Investigators

• Sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
• Collaborators: Germans Trias i Pujol Hospital; Institut Catala de Salut; Department of Health, Generalitat de Catalunya; Laboratorios Rubió; Laboratorios Gebro Pharma SA

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2020
• Primary Completion (Actual): June 15, 2020
• Study Completion (Actual): June 15, 2020

Study Registration Dates

• First Submitted: March 5, 2020
• First Submitted That Met QC Criteria: March 7, 2020
• First Posted (Actual): March 11, 2020

Study Record Updates

• Last Update Posted (Actual): June 30, 2020
• Last Update Submitted That Met QC Criteria: June 26, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: HCQ4COV19; 2020-001031-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Open access
• IPD Sharing Time Frame: 30 days after start of treatment
• IPD Sharing Access Criteria: Open access for everybody
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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