Cardiovascular Diseases, Hepatitis C, Hiv
Conditions
Keywords
Cardiovascular Disease
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.
Interventions
All approved direct-acting antivirals for hepatitis C will be used as the intervention.
PROCEDURECardiac MRI
Cardiac MRI to assess for myocardial function and fibrosis
Sponsors
National Institutes of Health (NIH)
Merck Sharp & Dohme LLC
University of Maryland, Baltimore
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cardiovascular Disease Risk From Baseline to After Functional Cure of Hepatitis C, as Measured by High-sensitivity C-reactive Protein | Baseline to 72 weeks after functional cure of HCV | Change in high-sensitivity C-reactive protein |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Change in the cardiac biomarkers Troponin I and Troponin T |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HIV Mono-Infected Patients infected with HIV only, and not currently or previously infected with hepatitis C.
Cardiac MRI: Cardiac MRI to assess for myocardial function and fibrosis | 43 |
| Hepatitis C Mono-Infected Patients infected with Hepatitis C and have no evidence of active HIV or hepatitis B infection
Elbasvir / Grazoprevir Oral Tablet \[Zepatier\]: All approved direct-acting antivirals for hepatitis C will be used as the intervention.
Cardiac MRI: Cardiac MRI to assess for myocardial function and fibrosis | 37 |
| HIV and Hepatitis C Co-Infected Patients co-infected with HIV and hepatitis C, and have no evidence of active hepatitis B infection.
Elbasvir / Grazoprevir Oral Tablet \[Zepatier\]: All approved direct-acting antivirals for hepatitis C will be used as the intervention.
Cardiac MRI: Cardiac MRI to assess for myocardial function and fibrosis | 7 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Did not meet eligibility criteria | 13 | 7 | 4 |
| Overall Study | Lost to Follow-up | 1 | 5 | 2 |
Baseline characteristics
| Characteristic | HIV Mono-Infected | Total | HIV and Hepatitis C Co-Infected | Hepatitis C Mono-Infected |
|---|---|---|---|---|
| Age, Continuous | 52 years | 55 years | 56 years | 58 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 37 Participants | 75 Participants | 6 Participants | 32 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 8 Participants | 1 Participants | 3 Participants |
| Region of Enrollment United States | 43 participants | 87 participants | 7 participants | 37 participants |
| Sex: Female, Male Female | 19 Participants | 37 Participants | 1 Participants | 17 Participants |
| Sex: Female, Male Male | 24 Participants | 50 Participants | 6 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 1 / 37 | 0 / 7 |
| other Total, other adverse events | 0 / 43 | 0 / 37 | 0 / 7 |
| serious Total, serious adverse events | 0 / 43 | 0 / 37 | 0 / 7 |
Outcome results
Primary
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
Time frame: Baseline to 72 weeks after functional cure of HCV
Population: 13 participants were analyzed in the hepatitis C mono-infected group and 1 participant in the HIV-HCV co-infected group since other participants were lost to follow-up and week 72 data was available for these participants only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hepatitis C Mono-Infected | Change in Cardiovascular Disease Risk From Baseline to After Functional Cure of Hepatitis C, as Measured by High-sensitivity C-reactive Protein | 0.6 mg/L | Standard Deviation 0.96 |
| HIV and Hepatitis C Co-Infected | Change in Cardiovascular Disease Risk From Baseline to After Functional Cure of Hepatitis C, as Measured by High-sensitivity C-reactive Protein | 0 mg/L | Standard Deviation 0 |
Secondary
Change in Troponin I and Troponin T From Baseline to After Functional Cure of Hepatitis C
Change in the cardiac biomarkers Troponin I and Troponin T
Time frame: Baseline to 48 weeks after functional cure of HCV
Population: Data on troponin I and T were not collected for any of the participants, therefore the outcome cannot be reported