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Cardiovascular Disease in HIV and Hepatitis C: Risk Outcomes After Hepatitis C Eradication (CHROME)

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ClinicalTrials.gov Identifier: NCT03823911
Recruitment Status : Recruiting
First Posted : January 31, 2019
Last Update Posted : February 15, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Poonam Mathur, University of Maryland

Brief Summary:
This is an interventional, non-randomized, controlled prospective study to treat HCV in mono-infected and HIV co-infected individuals and compare cardiovascular risk outcomes to HIV mono-infected controls. This pilot study will demonstrate whether functional cure of HCV reduces myocardial injury and risk of cardiovascular disease.

Condition or disease Intervention/treatment Phase
Cardiovascular Diseases Hepatitis C Hiv Drug: Elbasvir / Grazoprevir Oral Tablet [Zepatier] Procedure: Cardiac MRI Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Cardiovascular Disease in HIV and Hepatitis C: Risk Outcomes After Hepatitis C Eradication
Actual Study Start Date : November 18, 2018
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : December 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: HIV Mono-Infected
Patients infected with HIV only, and not currently or previously infected with hepatitis C.
Procedure: Cardiac MRI
Cardiac MRI to assess for myocardial function and fibrosis

Experimental: Hepatitis C Mono-Infected
Patients infected with Hepatitis C and have no evidence of active HIV or hepatitis B infection
Drug: Elbasvir / Grazoprevir Oral Tablet [Zepatier]
All approved direct-acting antivirals for hepatitis C will be used as the intervention.
Other Names:
  • Sofosbuvir/Ledipasvir
  • Sofosbuvir/Velpatasvir
  • Glecaprevir/Pibrentasvir
  • Sofosbuvir/Velpatasvir/Voxilaprevir

Procedure: Cardiac MRI
Cardiac MRI to assess for myocardial function and fibrosis

Experimental: HIV and Hepatitis C Co-Infected
Patients co-infected with HIV and hepatitis C, and have no evidence of active hepatitis B infection.
Drug: Elbasvir / Grazoprevir Oral Tablet [Zepatier]
All approved direct-acting antivirals for hepatitis C will be used as the intervention.
Other Names:
  • Sofosbuvir/Ledipasvir
  • Sofosbuvir/Velpatasvir
  • Glecaprevir/Pibrentasvir
  • Sofosbuvir/Velpatasvir/Voxilaprevir

Procedure: Cardiac MRI
Cardiac MRI to assess for myocardial function and fibrosis




Primary Outcome Measures :
  1. Change in cardiovascular disease risk from baseline to after functional cure of hepatitis C, as measured by high-sensitivity C-reactive protein [ Time Frame: Baseline to 48 weeks after functional cure of HCV ]
    Change in high-sensitivity C-reactive protein


Secondary Outcome Measures :
  1. Change in troponin I and troponin T from baseline to after functional cure of hepatitis C [ Time Frame: Baseline to 48 weeks after functional cure of HCV ]
    Change in the cardiac biomarkers Troponin I and Troponin T



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age > or equal to 18 years old
  2. Able and willing to sign informed consent
  3. Chronically infected with any HCV genotype (1a, 1b, 2, 3, 4, 5, or 6), defined as any individual with documentation of positive HCV antibody and positive HCV RNA test (HCV RNA of 2,000 IU/mL or greater)
  4. If HIV+, suppressed on a stable, protocol-approved, ARV regimen for ≥ 8 weeks prior to starting HCV treatment

    1. HIV RNA < 50 copies/mL (or < LLOQ if the local laboratory assay's LLOQ is ≥50 copies/mL) prior to Screening. Subjects with an isolated or unconfirmed HIV RNA > 50 copies/mL (or > LLOQ if the local laboratory assay's LLOQ is ≥50 copies/mL) are not excluded.
    2. CD4 count >100 cells/mm3
  5. Willing to have samples stored for future use
  6. If tested positive for NS5A resistance-associated polymorphisms or PEG-IFN and ribavirin experienced, able to tolerate ribavirin-containing regimen for 16 weeks. Ribavirin will be administered at the discretion of the PI.
  7. Women of childbearing potential who receive ribavirin will have to be willing to commit to abstinence from sexual activity, or use of two forms of contraceptive during treatment and for the 6 months after completion of ribavirin. Men receiving ribavirin who are sexually active with women will also have to be willing to commit to abstinence from sexual activity, or use of two forms of contraceptive during treatment and for the 6 months after completion of ribavirin.

Exclusion Criteria:

  1. Decompensated liver disease (Childs Pugh B or C)
  2. Unable to comply with research study visits
  3. Poor venous access not allowing screening laboratory collection
  4. Have any condition that the investigator considers a contraindication to study participation
  5. Pregnant or breastfeeding woman
  6. Prior HCV treatment with Direct-Acting Antivirals. Note: Patients who are treatment-experienced with PEG-IFN/RBV will not be excluded; their inclusion in the study will be considered by the PI.
  7. HIV+ patients with prior HCV treatment who achieved sustained virologic response (SVR)/ functional cure
  8. Use of a concomitant medication that is contraindicated with the use of the DAA for HCV treatment (per package insert)
  9. Coinfection with HCV and HBV, in partcular HBsAg + patients.

    a. Patients with HBcAb+ will not be excluded, but will have HBV DNA levels checked and will be monitored while on DAA therapy and medically managed as considered appropriate by the PI.

  10. Have any condition that the investigator considers a contraindication to study participation or not eligible per standard of care for HCV treatment
  11. Patients with the following devices are excluded from participating in the cardiovascular MRI study:

    • Central nervous system aneurysm clip
    • Implanted neural stimulator
    • Implanted cardiac pacemaker or defibrillator
    • Cochlear implant
    • Ocular foreign body (e.g. metal shavings)
    • Implanted insulin pump
    • Metal shrapnel or bullet
  12. The following groups of people are also excluded from participating in the cardiovascular MRI study:

    • Patients with stable renal disease (estimated glomerular filtration rate (eGFR)<30ml/min/1.73m2 body surface area. The eGFR must be within two weeks of the the MRI exam.
    • Patients with acute renal disease.
  13. Patients who choose to have the cardiac MRI and are over 60 years of age, have a history of renal failure, or have type I or II diabetes mellitus must have laboratory tests the same day as the MRI exam.
  14. Positive urine drug screen at screening. Not all patients with positive drug screen will be excluded; decision will be made by the PI.

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): NCT03823911


Contacts
Contact: Chloe Gross, RN 3014018016 cgross@ihv.umaryland.edu
Contact: Rachel Silk, RN 3013267652 rsilk@ihv.umaryland.edu

Locations
United States, District of Columbia
Unity Parkside Health Center Recruiting
Washington, District of Columbia, United States, 20019
Contact: Chloe Gross, RN    301-401-8016    cgross@ihv.umaryland.edu   
Contact: Poonam Mathur, DO    4433260506    pmathur@ihv.umaryland.edu   
Sponsors and Collaborators
University of Maryland
National Institutes of Health (NIH)
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Poonam Mathur, DO University of Maryland

Responsible Party: Poonam Mathur, Assistant Professor, University of Maryland
ClinicalTrials.gov Identifier: NCT03823911     History of Changes
Other Study ID Numbers: HP-00081300
First Posted: January 31, 2019    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Stored samples will be sent to the Institute of Human Virology at the University of Maryland and to BHF Centre for Cardiovascular Sciences:

Individuals with new seroconversion to HIV will have samples sent for viral sequencing and phylogenetic analysis. Individuals with detectable HCV RNA after completion of HCV treatment or new infection during the follow up period will have current sample, and baseline stored sample sent for viral sequencing and phylogenetic analysis.

In addition, we will study the viral and host immunity to HCV and HIV in all patients. The results will be used to characterize each individual with regards to immune status and chronicity of disease.

Supporting Materials: Study Protocol

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Poonam Mathur, University of Maryland:
Cardiovascular Disease

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Viral, Human
Cardiovascular Diseases
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Sofosbuvir
Sofosbuvir-velpatasvir drug combination
Elbasvir-grazoprevir drug combination
Antiviral Agents
Anti-Infective Agents