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Protocol Details

Cardiovascular Disease in HIV and Hepatitis C: Risk Outcomes after Hepatitis C Eradication

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

19-CC-0055

Sponsoring Institute

National Institutes of Health Clinical Center (CC)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required

Yes

Population Exclusion(s)

Children

Keywords

Sustained Virologic Response;
Myocardial Infection;
Directly Acting Antiviral;
Cardiac MRI;
Cardiovascular Biomarkers

Recruitment Keyword(s)

None

Condition(s)

Hepatitis C;
HIV;
Cardiovascular Disease

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Drug: Elbasvir/Grazoprevir Oral Tablets
Procedure/Surgery: Cardiac MRI

Supporting Site

NIH Clinical Center

Background:

People living with HIV (PLWH) have a 50% higher risk of heart attack than the general population. Highly active antiretroviral therapy (HAART) has many benefits for PLWH. These include a longer life span. But living longer makes PLWH prone to health issues for all people their age, like cardiovascular disease (CVD). Plus, HAART itself is a risk factor for CVD. The virus hepatitis C (HCV) is another infection that causes ill health and death. People who have HIV and HCV have a magnified risk of CVD. Researchers want to see if treating HCV lowers the risk of CVD for these people.

Objectives:

To treat HCV in people with HCV alone and people with both HCV and HIV, and compare heart disease risk to people with HIV alone.

Eligibility:

Adults ages 18 70 who have HIV, HCV, or both.

Design:

Participants will be screened at their clinics.

Some participants will have a cardiac magnetic resonance imaging (MRI) scan. They will lie in a machine that uses magnets and radio waves to take pictures of the heart. A medicine will be injected into their vein to brighten up the image of their heart, to see where blood flows. Heart rate and blood pressure will be monitored. The MRI does not use radiation.

Participants who have HCV will get standard care and monitoring. They will get direct-acting antiviral treatment.

Participants who have just HIV will get standard care.

After about 73 weeks of treatment, participants who had MRI will repeat it.

Some participants will be required to use 2 forms of birth control throughout the study.

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Eligibility

SUBJECTS INCLUSION CRITERIA:

To be eligible for participation on this protocol, a participant must satisfy all of the following conditions:

-Age greater than or equal to 18 years old

-Able and willing to sign informed consent

-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)

-If HIV+, suppressed on a stable, protocol-approved, ARV regimen for greater than or equal to 8 weeks prior to enrolling in the study

--HIV RNA < 50 copies/mL (or < LLOQ if the local laboratory assay s LLOQ is greater than or equal to 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 greater than or equal to 50 copies/mL) are not excluded.

--CD4 count >100 cells/mm3

-Willing to have samples stored for future use

-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.

-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.

SUBJECTS EXCLUSION CRITERIA:

A participant will be ineligible to participate in this study if any of the following criteria are met:

-Decompensated liver disease (Childs Pugh B or C)

-Unable to comply with research study visits

-Poor venous access not allowing screening laboratory collection

-Have any condition that the investigator considers a contraindication to study participation

-Pregnant or breastfeeding woman

-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.

-HIV+ patients with prior HCV treatment who achieved sustained virologic response (SVR)/ functional cure

-Use of a concomitant medication that is contraindicated with the use of the DAA for HCV treatment (per package insert)

-Coinfection with HCV and HBV, in particular HBsAg + patients.

--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.

-Have any condition that the investigator considers a contraindication to study participation or not eligible per standard of care for HCV treatment

-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

-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 MRI exam.

--Patients with acute renal disease.

-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.

-Positive urine drug screen at screening. Not all patients with positive drug screen will be excluded; decision will be made by the PI.


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Citations:

Sulkowski MS, Eron JJ, Wyles D, Trinh R, Lalezari J, Wang C, Slim J, Bhatti L, Gathe J, Ruane PJ, Elion R, Bredeek F, Brennan R, Blick G, Khatri A, Gibbons K, Hu YB, Fredrick L, Schnell G, Pilot-Matias T, Tripathi R, Da Silva-Tillmann B, McGovern B, Campbell AL, Podsadecki T. Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. JAMA. 2015 Mar 24-31;313(12):1223-31. doi: 10.1001/jama.2015.1328.

Chew KW, Liu CY, Ambale-Venkatesh B, Liao D, Horwich TB, Lima JAC, Bluemke DA, Paul Finn J, Butt AA, Currier JS. Subclinical myocardial disease by cardiac magnetic resonance imaging and spectroscopy in healthy HIV/Hepatitis C virus-coinfected persons. J Int Med Res. 2017 Dec;45(6):1693-1707. doi: 10.1177/0300060517708919. Epub 2017 Jun 12.

Freiberg MS, Chang CC, Kuller LH, Skanderson M, Lowy E, Kraemer KL, Butt AA, Bidwell Goetz M, Leaf D, Oursler KA, Rimland D, Rodriguez Barradas M, Brown S, Gibert C, McGinnis K, Crothers K, Sico J, Crane H, Warner A, Gottlieb S, Gottdiener J, Tracy RP, Budoff M, Watson C, Armah KA, Doebler D, Bryant K, Justice AC. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med. 2013 Apr 22;173(8):614-22. doi: 10.1001/jamainternmed.2013.3728.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Henry Masur, M.D.
National Institutes of Health Clinical Center (CC)
NIHBC 10 - CLINICAL CENTER BG RM 2C145
10 CENTER DR
BETHESDA MD 20892
(301) 496-9320
hmasur@cc.nih.gov

Rachel E. Silk, R.N.
National Institutes of Health Clinical Center (CC)
National Institutes of Health
Building 10
Room 2C145
10 Center Drive
Bethesda, Maryland 20892
(202) 857-5219
silkr@mail.nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1
ccopr@nih.gov

Clinical Trials Number:

NCT03823911

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