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

NCT03823911 | Completed Phase 4 Results FDA Drug FDA Device

• 1 other identifier: HP-00081300
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 2

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

Keywords

Cardiovascular Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change in Troponin I and Troponin T From Baseline to After Functional Cure of Hepatitis C

  Baseline to 48 weeks after functional cure of HCV

Study Arms (3)

HIV Mono-Infected

ACTIVE COMPARATOR

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

Procedure: Cardiac MRI

Hepatitis C Mono-Infected

EXPERIMENTAL

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

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

HIV and Hepatitis C Co-Infected

EXPERIMENTAL

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

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

Interventions

Elbasvir / Grazoprevir Oral Tablet [Zepatier] DRUG

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

Also known as: Sofosbuvir/Ledipasvir, Sofosbuvir/Velpatasvir, Glecaprevir/Pibrentasvir, Sofosbuvir/Velpatasvir/Voxilaprevir

HIV and Hepatitis C Co-Infected; Hepatitis C Mono-Infected

Cardiac MRI PROCEDURE

Cardiac MRI to assess for myocardial function and fibrosis

HIV Mono-Infected; HIV and Hepatitis C Co-Infected; Hepatitis C Mono-Infected

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> or equal to 18 years old
• Able and willing to sign informed consent
• 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)
• If HIV+, suppressed on a stable, protocol-approved, ARV regimen for ≥ 8 weeks prior to starting HCV treatment
• 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.
• CD4 count \>100 cells/mm3
• Willing to have samples stored for future use
• 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.
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Institutes of Health (NIH): collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Unity Parkside Health Center

Washington D.C., District of Columbia, 20019, United States

Location

Institute of Human Virology, CRU

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Cardiovascular Diseases; Hepatitis C; Acquired Immunodeficiency Syndrome

Interventions

elbasvir; grazoprevir; elbasvir-grazoprevir drug combination; ledipasvir, sofosbuvir drug combination; sofosbuvir-velpatasvir drug combination; glecaprevir and pibrentasvir; sofosbuvir velpatasvir voxilaprevir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; HIV Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Dr. Poonam Mathur
• Organization: Institute of Human Virology, University of Maryland School of Medicine

pmathur@ihv.umaryland.edu

410-706-4745

Study Officials

• Poonam Mathur, DO

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: January 31, 2019
• Study Start: November 18, 2018
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: May 22, 2023
• Results First Posted: May 22, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

US (2)