A Single-arm Evaluation of the Effect of HCV Treatment on Cardiovascular Disease Risk (HEART-C)

A Single-arm Evaluation of the Effect of Elbasvir/Grazoprevir on Cardiometabolic Parameters in Patients With Hepatitis C Infection and Underlying Metabolic Disease

This study will assess the effect of treatment for hepatitis C virus (HCV) on cardiovascular disease risk. The study will enroll men and women who are infected with HCV and have underlying metabolic disease. All participants will receive a 12-week course of an HCV treatment (elbasvir/grazoprevir). Cardiovascular disease risk will be evaluated at baseline, week 4 on treatment, 12 weeks post-treatment, and 52 weeks post-treatment through noninvasive measurements of endothelial function, insulin resistance, liver fibrosis and steatosis, and circulating blood biomarkers.

Study Overview

• Status: Withdrawn
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Elbasvir/grazoprevir

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90025
      • UCLA CARE Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women ≥ 18 years of age.
• Presence of HCV infection for at least 12 weeks
• Serum or plasma HCV RNA > lower limit of quantification or detection at any time before or at the time of screening, and the absence of intervening HCV treatment
• Absence of HIV infection
• HCV treatment-naïve OR HCV treatment-experienced with PEG-IFN/RBV only (no prior HCV DAA exposure)
• Genotype 1 or 4 HCV infection. If HCV genotype 1a infection is present, absence of genotype 1a NS5A resistance associated substitutions (RASs) at amino acid positions 28, 30, 31, and 93 must be documented at screening

• Evidence of metabolic disease defined as:

  1. Insulin resistance or impaired glucose tolerance by one of the following:

     • HOMA-IR ≥2.5 at screening
     • Hemoglobin A1c 5.7-6.4% at screening
     • Diabetes mellitus with hemoglobin A1c <7% at screening and never on more than one oral hypoglycemic agent, as well as never requiring insulin

     OR

  2. Metabolic Syndrome, defined as at least 3 of the following:

     • Waist circumference ≥102 cm for men and ≥ 88 cm for women
     • Serum triglyceride level ≥150 mg/dL or on a triglyceride lowering agent
     • Serum high-density lipoprotein (HDL) cholesterol <40 mg/dL in men and <50 mg/dL in women or drug treatment for low HDL cholesterol
     • Blood pressure ≥130/85 mmHg or drug treatment for elevated blood pressure
     • Fasting blood glucose ≥100 mg/dL
• Ability and willingness of subject to provide written informed consent

Exclusion Criteria:

• History of decompensated liver disease (Child Pugh Class B or C)
• Albumin below 3 g/dL
• Platelet count below 75,000
• HBsAg positivity.
• Pregnancy or breastfeeding
• Inability to conform to the following drug interruptions for PAT testing, whether due to safety (determined by the investigator) or willingness: No caffeine or recreational or prescription stimulant use for 24 hours prior; no nicotine for 4 hours prior; no vigorous exercise for 12 hours prior; stopping of beta blockers, short-acting calcium channel blockers (CCBs), nitrates, angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin-receptor blockers (ARBs), and renin-inhibitors for 24 hours prior; and stopping of long acting CCBs 48 hours prior to testing.
• Use of anticoagulant or antiplatelet agents (other than aspirin ≤ 325 mg orally daily) within 1 week prior to study entry or anticipated need for these agents for >7 days during the study follow-up period.
• Use of contraindicated concomitant medications, including OATP1B1/3 inhibitors and strong CYP3A inducers
• Serious illness including acute liver-related disease and malignancy requiring systemic treatment or hospitalization within 12 weeks prior to study entry.
• History of major organ transplantation with an existing functional graft and on immunosuppressive therapy.
• History of known vascular disorder or autoimmune processes including Crohn's disease, ulcerative colitis, severe psoriasis, rheumatoid arthritis, and cryoglobulinemia that may affect vascular studies.
• Decompensated congestive heart failure or acute cardiovascular event (such as stroke, myocardial infarction, arrhythmia, acute peripheral arterial insufficiency) within 6 months prior to study entry
• Use of immune-based therapies or systemic corticosteroids which may affect vascular studies or inflammatory/endothelial biomarkers within 12 weeks prior to study entry
• Advanced renal insufficiency as defined by glomerular filtration rate (GFR) < 30 mL/min/1.73 m2 or treatment by dialysis
• Anticipated inability to comply with research study visits as determined by the investigator
• Poor venous access not allowing screening laboratory collection
• Having any condition that the investigator considers a contraindication to study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All participants; Intervention: Elbasvir/grazoprevir	Drug: Elbasvir/grazoprevir; Daily fixed-dose combination (FDC) elbasvir (EBR) (50 mg)/grazoprevir (GZR) (100 mg) for 12 weeks; Other Names: Zepatier, serial number 86336186

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in reactive hyperemia index (RHI) by peripheral arterial tonometry (PAT)	Baseline to 12 weeks after end of EBR/GZR treatment.

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in insulin resistance by HOMA-IR	Baseline to 12 weeks after end of treatment
Change in reactive hyperemia index (RHI) by PAT	Baseline to week 4 on treatment
Change in reactive hyperemia index (RHI) by PAT	Baseline to 52 weeks after end of treatment
Change in insulin resistance by HOMA-IR	Baseline to week 4 on treatment
Change in insulin resistance by HOMA-IR	Baseline to 52 weeks after end of treatment
Change in hemoglobin A1c	Baseline to week 4, baseline to 12 weeks after end of treatment, and baseline to 52 weeks after end of treatment
Change in total and LDL cholesterol levels	Baseline to week 4, baseline to 12 weeks after end of treatment, and baseline to 52 weeks after end of treatment
Change in levels of each soluble biomarker (sCD163, sCD14, sICAM-1, PAI-1, sE-selectin, oxidized LDL, Lp-PLA2, and lipoprotein particle quantification)	Baseline to week 4, baseline to 12 weeks after end of treatment, and baseline to 52 weeks after end of treatment
Cross-sectional levels of each soluble biomarker (sCD163, sCD14, sICAM-1, PAI-1, sE-selectin, oxidized LDL, Lp-PLA2, and lipoprotein particle quantification) at each time point for correlation with RHI	Baseline, week 4, post-treatment weeks 12 and 52
Cross-sectional fibrosis score in kPa by transient elastography (TE) for correlation with RHI and soluble biomarkers	Baseline and 12 and 52 weeks after end of treatment
Cross-sectional steatosis score in dB/m by CAP for correlation with RHI and soluble biomarkers at the same time points	Baseline and 12 and 52 weeks after end of treatment
Change in fibrosis score by transient elastography	Baseline to 52 weeks after end of treatment
Change in hepatic steatosis score by CAP	Baseline to 52 weeks after end of treatment

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Kara W Chew, M.D., M.S., University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2018
• Primary Completion (Anticipated): June 1, 2019
• Study Completion (Anticipated): April 1, 2020

Study Registration Dates

• First Submitted: June 29, 2018
• First Submitted That Met QC Criteria: June 29, 2018
• First Posted (Actual): July 12, 2018

Study Record Updates

• Last Update Posted (Actual): August 7, 2018
• Last Update Submitted That Met QC Criteria: August 3, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Inflammation; Insulin resistance; Endothelial function; Cardiovascular disease risk; Hepatitis C virus; Metabolic 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; Metabolic Diseases; Anti-Infective Agents; Antiviral Agents; Grazoprevir; Elbasvir-grazoprevir drug combination
• Other Study ID Numbers: 18-000650

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No