Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04304053
Recruitment Status : Recruiting
First Posted : March 11, 2020
Last Update Posted : April 16, 2020
Sponsor:
Collaborators:
Germans Trias i Pujol Hospital
Department of Health, Generalitat de Catalunya
FUNDACIÓN FLS DE LUCHA CONTRA EL SIDA, LAS ENFERMEDADES INFECCIOSAS Y LA PROMOCIÓN DE LA SALUD Y LA CIENCIA
Laboratorios Gebro Pharma SA
Laboratorios Rubió
Institut Catala de Salut
Information provided by (Responsible Party):
Oriol Mitja, Germans Trias i Pujol Hospital

Brief Summary:
The investigators plan to evaluate the efficacy of the 'test and treat' strategy of infected patients and prophylactic chloroquine treatment to all contacts. The strategy entails decentralized COVID-19 testing and starting chloroquine treatment immediately in all who are found to be infected. As viral loads decline to undetectable levels, the probability of onward transmission is reduced to very low levels. Such evaluation will require prospective surveillance to assess the population-level effect of transmission prevention.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Treatment and prophylaxis Other: Standard Public Health measures Phase 3

Detailed Description:

Previous research on influenza has indicated that antiviral drugs administered before o short after symptom onset can reduce infectiousness to others by reducing viral loads in the respiratory secretions of patients.

Lopinavir/ritonavir, a protease inhibitor used to treat HIV/AIDS, was found to block COVID-19 infection in vitro at low-micromolar concentration, with a half-maximal effective concentration (EC50) of 8.5 μM. China's guidelines were set up in January 2020 and treated hospitalized patients with lopinavir/ritonavir, either alone or with various combinations. Darunavir (DRV)/Cobicistat, is also a protease inhibitor used to treat and prevent HIV/AIDS. Its as effective as lopinavir/ritonavir for the treatment of HIV/AIDS and better tolerated because the adverse effects rate is lower (diarrhea 2% vs 27%).

In last week DRV has been shown to exert no activity on the SARS-CoV-2 clinical studies and is therefore withdrawn for futility. Although LPVr shows in vitro efficacy against SARS-CoV-2 at elevated total drug concentrations, human clinical trials have not demonstrated superiority of LPVr vs Placebo. It has been considered that the magnitude of the possible clinical benefit of LPVr if it is started in the early stages of the disease is small and does not compensate for the gastrointestinal and renal toxicity of the drug.

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3040 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Cluster-randomized clinical trial
Masking: None (Open Label)
Masking Description: Open label
Primary Purpose: 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)
Actual Study Start Date : March 18, 2020
Estimated Primary Completion Date : June 15, 2020
Estimated Study Completion Date : June 15, 2020

Arm Intervention/treatment
Active Comparator: No Intervention- SARS-CoV-2 surveillance

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. Contacts will also complete a survey collecting demographic, epidemiological and clinical data and provides a swab for RT-PCR testing at baseline and day 14. Rescue therapy with Hydroxychloroquine will be administered when a contact in the control arm develops symptoms consistent with COVID-19 and positive PCR.

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
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. Index case receives Hydroxychloroquine. Contacts receive Hydroxychloroquine prophylaxis. Index case contacts will also complete a survey collecting demographic, epidemiological and clinical and provides a swab for RT-PCR testing at baseline and day 14.
Drug: Treatment and prophylaxis

hydroxychloroquine (200mg tablets) 800mg on day 1, and 400mg on days 2,3,4, 5, 6 and 7

Contacts will be offered a prophylactic regimen of hydroxychloroquine (200mg tablets) 800mg on day 1, and 400mg on days 2,3,4.


Other: Standard Public Health measures
Isolation of patient and contact tracing as per national guidelines.




Primary Outcome Measures :
  1. Effectiveness of chemoprophylaxis assessed by incidence of secondary COVID-19 cases [ Time Frame: Up to 14 days after start of treatment ]
    Incidence of secondary cases among contacts of a case and contacts of contacts


Secondary Outcome Measures :
  1. The virological clearance rate of throat swabs, sputum, or lower respiratory tract secretions at days 3 [ Time Frame: 3 and 7 days after start of treatment ]
  2. The mortality rate of subjects at weeks 2 [ Time Frame: Up to 14 days after start of treatment ]
  3. Proportion of participants that drop out of study [ Time Frame: Up to 14 days after start of treatment ]
  4. Proportion of participants that show non-compliance with study drug [ Time Frame: Up to 14 days after start of treatment ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Inclusion Criteria for a contact:

  1. Asymptomatic individuals exposed to a PCR confirmed COVID19 case within 5 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04304053


Contacts
Layout table for location contacts
Contact: oriol Mitja, PhD 0034 934651072 oriolmitja@hotmail.com
Contact: Laia Bertran 0034 934651072

Locations
Layout table for location information
Spain
Departament de Salut Recruiting
Barcelona, Spain
Contact: Oriol Mitjà       omitja@flsida.org   
Sponsors and Collaborators
Fundacio Lluita Contra la SIDA
Germans Trias i Pujol Hospital
Department of Health, Generalitat de Catalunya
FUNDACIÓN FLS DE LUCHA CONTRA EL SIDA, LAS ENFERMEDADES INFECCIOSAS Y LA PROMOCIÓN DE LA SALUD Y LA CIENCIA
Laboratorios Gebro Pharma SA
Laboratorios Rubió
Institut Catala de Salut
Layout table for additonal information
Responsible Party: Oriol Mitja, Prof (Ass) Infectious Disease and Global Health, Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier: NCT04304053    
Other Study ID Numbers: HCQ4COV19
2020-001031-27 ( EudraCT Number )
First Posted: March 11, 2020    Key Record Dates
Last Update Posted: April 16, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Open access
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: 30 days after start of treatment
Access Criteria: Open access for everybody
URL: http://www.estudicovid19.org

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No