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

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Hepatitis C; Hiv
• Intervention / Treatment: Procedure: Cardiac MRI; Drug: Elbasvir / Grazoprevir Oral Tablet [Zepatier]

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20019
      • Unity Parkside Health Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Institute of Human Virology, CRU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cardiovascular Disease Risk From Baseline to After Functional Cure of Hepatitis C, as Measured by High-sensitivity C-reactive Protein	Change in high-sensitivity C-reactive protein	Baseline to 72 weeks after functional cure of HCV

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Troponin I and Troponin T From Baseline to After Functional Cure of Hepatitis C	Change in the cardiac biomarkers Troponin I and Troponin T	Baseline to 48 weeks after functional cure of HCV

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: Merck Sharp & Dohme LLC; National Institutes of Health (NIH)
• Investigators: Principal Investigator: Poonam Mathur, DO, University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2018
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: January 28, 2019
• First Submitted That Met QC Criteria: January 28, 2019
• First Posted (Actual): January 31, 2019

Study Record Updates

• Last Update Posted (Actual): May 22, 2023
• Last Update Submitted That Met QC Criteria: May 19, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Cardiovascular Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Cardiovascular Diseases; Hepatitis; Hepatitis A; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Sofosbuvir-velpatasvir drug combination; Velpatasvir; Ledipasvir; Grazoprevir; Elbasvir-grazoprevir drug combination
• Other Study ID Numbers: HP-00081300

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• 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