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History of Changes for Study: NCT04304053
Treatment of COVID-19 Cases and Chemoprophylaxis of Contacts as Prevention (HCQ4COV19)
Latest version (submitted June 26, 2020) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 March 7, 2020 None (earliest Version on record)
2 March 11, 2020 Study Design, Eligibility, Sponsor/Collaborators and Study Status
3 March 13, 2020 Study Identification, Arms and Interventions, Sponsor/Collaborators and Study Status
4 March 22, 2020 Recruitment Status, Study Status, Study Identification, Sponsor/Collaborators, Contacts/Locations, Eligibility, Arms and Interventions and Oversight
5 April 6, 2020 IPDSharing, Contacts/Locations and Study Status
6 April 14, 2020 Arms and Interventions, Study Description, Eligibility, Outcome Measures and Study Status
7 June 7, 2020 Recruitment Status, Outcome Measures, Study Status, Contacts/Locations, Study Description and Arms and Interventions
8 June 10, 2020 Outcome Measures, Arms and Interventions, Study Design, Study Description and Study Status
9 June 22, 2020 Outcome Measures, Arms and Interventions, Study Design, Study Description and Study Status
10 June 26, 2020 Recruitment Status, Study Status, Arms and Interventions, Study Design, Study Description, Sponsor/Collaborators, Eligibility and Outcome Measures
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Changes (Side-by-Side) for Study: NCT04304053
March 7, 2020 (v1) -- April 14, 2020 (v6)

Changes in: Study Status, Study Identification, IPDSharing, Arms and Interventions, Sponsor/Collaborators, Study Design, Study Description, Contacts/Locations, Eligibility, Outcome Measures and Oversight

Study Identification
Unique Protocol ID: CQ4COV19 HCQ4COV19
Brief Title: Treatment of Mild Cases and Chemoprophylaxis of Contacts as Prevention of the COVID-19 Epidemic (CQ4COV19)Treatment of COVID-19 Cases and Chemoprophylaxis of Contacts as Prevention (HCQ4COV19)
Official Title: Antiviral Treatment of COVID-19 Confirmed Cases and Ring Chloroquine Chemoprevention in Close Contacts: a Cluster Randomized Clinical Trial 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)
Secondary IDs: 2020-001031-27 [EudraCT Number]
Study Status
Record Verification: March 2020 April 2020
Overall Status: Not yet recruiting Recruiting
Study Start: March 15, 2020 March 18, 2020
Primary Completion: July 15, 2020 [Anticipated ] June 15, 2020 [Anticipated ]
Study Completion: July 15, 2020 [Anticipated ] June 15, 2020 [Anticipated ]
First Submitted: March 5, 2020 March 5, 2020
First Submitted that
Met QC Criteria:
March 7, 2020 March 7, 2020
First Posted: March 11, 2020 [Actual ] March 11, 2020 [Actual ]
Last Update Submitted that
Met QC Criteria:
March 7, 2020 April 14, 2020
Last Update Posted: March 11, 2020 [Actual ] April 16, 2020 [Actual ]
Sponsor/Collaborators
Sponsor: Lihir Medical Centre Fundacio Lluita Contra la SIDA
Responsible Party: Principal Investigator
Investigator: Oriol Mitja
Official Title: Prof (Ass) Infectious Disease and Global Health
Affiliation: Germans Trias i Pujol Hospital
Principal Investigator
Investigator: Oriol Mitja
Official Title: Prof (Ass) Infectious Disease and Global Health
Affiliation: Germans Trias i Pujol Hospital
Collaborators: Germans Trias i Pujol Hospital
Department of Health, Generalitat de Catalunya
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
Oversight
U.S. FDA-regulated Drug: No No
U.S. FDA-regulated Device: No No
Data Monitoring: Yes Yes
Study Description
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 antiviral darunavir/cobicistat plus 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.

Drug interventions in this protocol will follow the Spanish law about off-label use of medicines.

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.
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%).

Another promising drug is chloroquine, that showed excellent in vitro results and strong antiviral effects on SARS-CoV infection of primate cells. Results from n=100 patients have shown superiority to the control treatment in improving lung imaging findings, promoting virus reversion to negative and shortening the disease.

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.

Conditions
Conditions: COVID-19 COVID-19
Keywords:
Study Design
Study Type: InterventionalInterventional
Primary Purpose: PreventionPrevention
Study Phase: Phase 2/Phase 3Phase 3
Interventional Study Model: Parallel Assignment Parallel Assignment
Cluster-randomized clinical trial Cluster-randomized clinical trial
Number of Arms: 22
Masking: None (Open Label)None (Open Label)
Allocation: RandomizedRandomized
Enrollment: 2900 [Anticipated ] 3040 [Anticipated ]
Arms and Interventions
Arms Assigned Interventions
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.

Subjects exhibiting Acute Respiratory Infection (ARI) symptoms at a participating health care services complete a survey collecting demographic and clinical data and provide a swab for RT-PCR testing. Isolation of patient and contact tracing as per guidelines.
Standard Public Health measures
Isolation of patient and contact tracing as per national guidelines.
Experimental: Testing, treatment and prophylaxis of SARS-CoV-2
Subjects exhibiting ARI symptoms at a participating hospital complete a survey collecting demographic and clinical data and provide a swab to be tested on-site with a molecular assay. Isolation of patient and contact tracing as per guidelines. Case receive an antiviral if tested positive (Chloroquine and darunavir/cobicistat). Contacts receive Chloroquine prophylaxis 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: Antiviral Treatment and prophylaxis

darunavir 800 mg / cobicistat 150 mg tablets (oral, 1 tablet q24h, taking for 7 days) and chloroquine (ResochinR chloroquine phosphate 250mg tablets, equivalent to 155mg chloroquine base) 1 g of chloroquine phosphate on days 1 and 2 and 0,5 g on day 3. 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 chloroquine hydroxychloroquine ( ResochinR chloroquine phosphate 250 200mg tablets , equivalent to 155 ) 800mg chloroquine base;) 1 g of chloroquine phosphate on day 1, and 2 and 0,5 g 400mg on days 2,3,4.

Standard Public Health measures
Isolation of patient and contact tracing as per national guidelines.
Outcome Measures
Primary Outcome Measures:
1. Effectiveness of chemoprophylaxis assessed by incidence of secondary COVID-19 cases
Incidence of secondary cases among contacts of a case and contacts of contacts

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

[Time Frame: Up to 14 days after start of treatment ]
Secondary Outcome Measures:
2. The virological clearance rate of throat swabs, sputum, or lower respiratory tract secretions at days 3
3 days after start of treatment
The virological clearance rate of throat swabs, sputum, or lower respiratory tract secretions at days 3
3 and 7 days after start of treatment
3. The mortality rate of subjects at weeks 2
Up to 14 days after start of treatment
The mortality rate of subjects at weeks 2
Up to 14 days after start of treatment
4. Proportion of participants that drop out of study
Up to 14 days after start of treatment
Proportion of participants that drop out of study
Up to 14 days after start of treatment
5. Proportion of participants that show non-compliance with study drug
Up to 14 days after start of treatment
Proportion of participants that show non-compliance with study drug
Up to 14 days after start of treatment
Eligibility
Minimum Age: 18 Years 18 Years
Maximum Age:
Sex: All All
Gender Based:
Accepts Healthy Volunteers: YesYes
Criteria:

Inclusion Criteria for a case:

  1. Patients who meet the requirements of the New Coronavirus Infection Diagnosis (Acute respiratory infection symptoms or acute cough alone and positive PCR)
  2. Aged ≥18 years male or female;
  3. Willing to take study medication
  4. Willing to comply with all study procedures, including repeat nasal swab at day 3
  5. Able to provide written, informed consent and/or assent

Exclusion Criteria for a case:

  1. 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;
  2. 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;
  3. With known history of cardiac arrhythmia (or QT prolongation syndrome);
  4. Unable to take drugs by mouth;
  5. With significantly abnormal liver function (Child Pugh C)
  6. Need of dialysis treatment, or GFR≤30 mL/min/1.73 m2;
  7. Participants with retinal disease, hearing loss;
  8. Participants with severe neurological and mental illness;
  9. Pregnant or lactating women;
  10. Inability to consent and/or comply with study protocol;
  11. Individuals with known hypersensitivity to the study drugs.

Inclusion Criteria for a contact:

  1. Patients who meet the definition of a contact according to the Catalan Public Health Department Guidelines
  2. Aged ≥18 years male or female;
  3. Willing to take study medication;
  4. Willing to comply with all study procedures;
  5. 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 retinal disease, hearing loss.

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.
Contacts/Locations
Central Contact: oriol Mitja, PhD
Telephone: 0034 934651072
Email: oriolmitja@hotmail.com
oriol Mitja, PhD
Telephone: 0034 934651072
Email: oriolmitja@hotmail.com
Central Contact Backup: Laia Bertran
Telephone: 0034 934651072
Laia Bertran
Telephone: 0034 934651072
Locations: Spain
Departament de Salut
[Recruiting]
Barcelona, Spain
Contact: Oriol Mitjà omitja@flsida.org
IPDSharing
Plan to Share IPD: No Yes
Open access
Supporting Information:
Supporting Information:
Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame:
Time Frame:
30 days after start of treatment
Access Criteria:
Access Criteria:
Open access for everybody
URL: URL: http://www.estudicovid19.org
References
Citations:
Links:
Available IPD/Information:

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