Clinical Trials

MainTitle

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

This study is currently recruiting participants. (see Contacts and Locations)

Verified December 2019 by Poonam Mathur, University of Maryland, Baltimore

Sponsor
University of Maryland, Baltimore

Collaborator
National Institutes of Health (NIH)
Merck Sharp & Dohme Corp.

Information provided by (Responsible Party)
Poonam Mathur, University of Maryland, Baltimore

ClinicalTrials.gov Identifier
NCT03823911

First received: January 28, 2019
Last updated: December 10, 2019
Last Verified: December 2019
History of Changes
Purpose

Purpose

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 Intervention Phase
Cardiovascular Diseases
Hepatitis C
Hiv

Drug : Elbasvir / Grazoprevir Oral Tablet [Zepatier]
Procedure : Cardiac MRI
Phase 4

Study Type: Interventional
Study Design: 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

Further study details as provided by Poonam Mathur, University of Maryland, Baltimore:

Primary Outcome Measures

  • 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:
  • 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

Estimated Enrollment: 90
Study Start Date: November 18, 2018
Estimated Study Completion Date: July 1, 2021
Estimated Primary Completion Date: July 1, 2021 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
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 Name:
  • 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 Name:
  • Sofosbuvir/Ledipasvir
  • Sofosbuvir/Velpatasvir
  • Glecaprevir/Pibrentasvir
  • Sofosbuvir/Velpatasvir/Voxilaprevir

Procedure: Cardiac MRI

Cardiac MRI to assess for myocardial function and fibrosis

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 70 Years  
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:
  • Decompensated liver disease (Childs Pugh B or C)
  • Unable to comply with research study visits
  • Poor venous access not allowing screening laboratory collection
  • Have any condition that the investigator considers a contraindication to study participation
  • Pregnant or breastfeeding woman
  • 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.
  • HIV+ patients with prior HCV treatment who achieved sustained virologic response (SVR)/ functional cure
  • Use of a concomitant medication that is contraindicated with the use of the DAA for HCV treatment (per package insert)
  • 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.
  • Have any condition that the investigator considers a contraindication to study participation or not eligible per standard of care for HCV treatment
  • 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
  • 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.
  • 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.
  • Positive urine drug screen at screening. Not all patients with positive drug screen will be excluded; decision will be made by the PI.

    contacts and locations

    Contacts and Locations

    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, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT03823911

    Contacts

    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: Rachel Silk, RN    301-326-7652    rsilk@ihv.umaryland.edu
    Contact: Poonam Mathur, DO    4433260506    pmathur@ihv.umaryland.edu
    United States, Maryland
    Institute of Human Virology, CRU Enrolling by invitation
    Baltimore, Maryland, United States, 21201

    Sponsors and Collaborators

    University of Maryland, Baltimore
    National Institutes of Health (NIH)
    Merck Sharp & Dohme Corp.

    Investigators

    Principal Investigator: Poonam Mathur, DO University of Maryland, Baltimore
    More Information

    More Information


    Responsible Party: Poonam Mathur, Assistant Professor, University of Maryland, Baltimore  
    ClinicalTrials.gov Identifier: NCT03823911   History of Changes  
    Other Study ID Numbers: HP-00081300  
    Study First Received: January 28, 2019  
    Last Updated: December 10, 2019  
    Individual Participant Data    
    Plan to Share IPD: Yes  

    Studies a U.S. FDA-regulated Drug Product: Yes  
    Studies a U.S. FDA-regulated Device Product: Yes  
    Product Manufactured in and Exported from the U.S.: No  

    Keywords provided by Poonam Mathur, University of Maryland, Baltimore:

    Cardiovascular Disease

    Additional relevant MeSH terms:
    Hepatitis A
    Hepatitis C
    Hepatitis
    Cardiovascular Diseases
    Sofosbuvir
    MK-5172
    Ledipasvir
    Velpatasvir
    Elbasvir-grazoprevir drug combination
    Sofosbuvir-velpatasvir drug combination

    ClinicalTrials.gov processed this data on May 24, 2020
    This information is provided by ClinicalTrials.gov.