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

Cardiovascular Diseases Clinical Trial

— CHROME  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03823911
• Other study ID #: HP-00081300
• Status: Completed
• Phase: Phase 4
• Start date: November 18, 2018
• Est. completion date: December 31, 2022

Study information

• Verified date: May 2023
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 87
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hiv

Intervention

Drug:
• Elbasvir / Grazoprevir Oral Tablet [Zepatier]
All approved direct-acting antivirals for hepatitis C will be used as the intervention.

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

Locations

Country	Name	City	State
United States	Institute of Human Virology, CRU	Baltimore	Maryland
United States	Unity Parkside Health Center	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
University of Maryland, Baltimore	Merck Sharp & Dohme LLC, National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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