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

NCT ID: NCT03823911

Last Updated: 2023-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-18
• Study Completion Date: 2022-12-31

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.

Conditions

Cardiovascular Diseases; Hepatitis C; Hiv

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

HIV Mono-Infected

Patients infected with HIV only, and not currently or previously infected with hepatitis C.

Group Type: ACTIVE_COMPARATOR

Cardiac MRI

Intervention Type: PROCEDURE

Cardiac MRI to assess for myocardial function and fibrosis

Hepatitis C Mono-Infected

Patients infected with Hepatitis C and have no evidence of active HIV or hepatitis B infection

Group Type: EXPERIMENTAL

Elbasvir / Grazoprevir Oral Tablet [Zepatier]

Intervention Type: DRUG

All approved direct-acting antivirals for hepatitis C will be used as the intervention.

Cardiac MRI

Intervention Type: PROCEDURE

Cardiac MRI to assess for myocardial function and fibrosis

HIV and Hepatitis C Co-Infected

Patients co-infected with HIV and hepatitis C, and have no evidence of active hepatitis B infection.

Group Type: EXPERIMENTAL

Elbasvir / Grazoprevir Oral Tablet [Zepatier]

Intervention Type: DRUG

All approved direct-acting antivirals for hepatitis C will be used as the intervention.

Cardiac MRI

Intervention Type: PROCEDURE

Cardiac MRI to assess for myocardial function and fibrosis

Interventions

Elbasvir / Grazoprevir Oral Tablet [Zepatier]

All approved direct-acting antivirals for hepatitis C will be used as the intervention.

Intervention Type: DRUG

Cardiac MRI

Cardiac MRI to assess for myocardial function and fibrosis

Intervention Type: PROCEDURE

Other Intervention Names

Sofosbuvir/Ledipasvir; Sofosbuvir/Velpatasvir; Glecaprevir/Pibrentasvir; Sofosbuvir/Velpatasvir/Voxilaprevir

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Poonam Mathur

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Poonam Mathur, DO

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Locations

Unity Parkside Health Center

Washington D.C., District of Columbia, United States

Institute of Human Virology, CRU

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HP-00081300

Identifier Type: -

Identifier Source: org_study_id