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

Sponsor

University of California, Los Angeles (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03585101

Collaborator

Merck Sharp & Dohme LLC (Industry)

Enrollment

Location

Arm

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: Elbasvir/grazoprevir	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2018

Anticipated Primary Completion Date :

Jun 1, 2019

Anticipated Study Completion Date :

Apr 1, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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

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