Clinical trial NCT03823911: Cardiovascular Disease in HIV and Hepatitis C: Risk Outcomes After Hepatitis C Eradication
Official title: Cardiovascular Disease in HIV and Hepatitis C: Risk Outcomes After Hepatitis C Eradication
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cardiovascular Diseases
Hepatitis C
Hiv
Keywords: Cardiovascular Disease
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Merck Sharp & Dohme LLC
First posted: 2019-01-31
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in Cardiovascular Disease Risk From Baseline to After Functional Cure of Hepatitis C, as Measured by High-sensitivity C-reactive Protein
timeFrame: Baseline to 72 weeks after functional cure of HCV
Secondary outcomes:
measure: Change in Troponin I and Troponin T From Baseline to After Functional Cure of Hepatitis C
timeFrame: Baseline to 48 weeks after functional cure of HCV
Other outcomes:
Locations:
city: Washington
country: United States
facility: Unity Parkside Health Center
state: District of Columbia
city: Baltimore
country: United States
facility: Institute of Human Virology, CRU
state: Maryland
Study officials:
affiliation: University of Maryland, Baltimore
name: Poonam Mathur, DO
role: PRINCIPAL_INVESTIGATOR
References: