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

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ClinicalTrials.gov Identifier: NCT03585101
Recruitment Status : Withdrawn (Funding no longer available)
First Posted : July 12, 2018
Last Update Posted : August 7, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Kara Chew, University of California, Los Angeles

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
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
Estimated Study Start Date : August 2018
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine


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 Name: Zepatier, serial number 86336186




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

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


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03585101


Locations
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United States, California
UCLA CARE Center
Los Angeles, California, United States, 90025
Sponsors and Collaborators
University of California, Los Angeles
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Kara W Chew, M.D., M.S. University of California, Los Angeles

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Responsible Party: Kara Chew, Assistant Clinical Professor of Medicine, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT03585101     History of Changes
Other Study ID Numbers: 18-000650
First Posted: July 12, 2018    Key Record Dates
Last Update Posted: August 7, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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

Keywords provided by Kara Chew, University of California, Los Angeles:
Hepatitis C virus
Endothelial function
Cardiovascular disease risk
Metabolic disease
Inflammation
Insulin resistance

Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Hepatitis
Metabolic Diseases
Cardiovascular Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
MK-5172
Antiviral Agents
Anti-Infective Agents