Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Heart Transplants From Hepatitis C-Positive Donors (HCV) (USHER)

November 18, 2021 updated by: University of Pennsylvania

Open-Labeled Trial Of Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Heart Transplants From Hepatitis C-Positive Donors

This study is being conducted to determine safety and effectiveness of transplanting hearts from Hepatitis C-positive donors into Hepatitis C-negative patients on the heart transplant waitlist, who will then be treated with Zepatier after transplantation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Open-labelled pilot clinical trial of Zepatier (MK-5172 and MK-8742/Grazoprevir + Elbasvir) in at least 20 HCV-negative subjects receiving a heart transplant from a HCV-positive donor. Eligible subjects will receive a heart transplant from a deceased-donor with genotype 1 or 4 HCV, and then will receive 12 weeks of Zepatier after heart transplantation when infection with HCV is confirmed in these heart transplant recipients. Treatment will be complete after 12 weeks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • New York Heart Association (NYHA) Class III or IV CHF refractory to maximal medical therapy (ACE inhibitor, B-blocker, digoxin and diuretics, resynchronization therapy or Implantable Cardioverter Defibrillator when applicable) and/or conventional surgery.
  • Inoperable coronary artery disease with intractable anginal symptoms
  • Malignant ventricular arrhythmias unresponsive to medical or surgical therapy
  • 18-65 years of age
  • Obtained agreement for participation from the transplant cardiology team
  • No evident contraindication to liver transplantation other than the underlying cardiac disorder
  • Able to travel to the University of Pennsylvania for routine post-transplant visits and study visits for a minimum of 6 months after transplantation
  • No active illicit substance abuse
  • Women must agree to use birth control in accordance with Mycophenolate Risk Evaluation and Mitigation Strategy (REMS) following transplant due to the increased risk of birth defects and/or miscarriage
  • Both men and women must agree to use at least one barrier method of birth control or remain abstinent following transplant due to risk of HCV transmission
  • Inclusion criteria for treatment (not for entry as study patient) will include any detectable HCV RNA by week 4 post-heart transplantation
  • Able to provide informed consent

Exclusion Criteria:

  • Hepatocellular carcinoma
  • HIV positive
  • HCV antibody positive and/or RNA positive
  • Hepatitis B surface antigen, core antibody, and/or DNA positive
  • Any other chronic liver disease (excluding non-alcoholic fatty liver disease (NAFLD) with abnormal liver enzymes
  • Persistently elevated liver transaminases
  • Congenital heart disease
  • Fibrosis by liver biopsy or total bilirubin > 2.5 with associated evidence of synthetic dysfunction.
  • Pregnant or nursing (lactating) women
  • Known allergy or intolerance to tacrolimus that would require post-transplant administration of cyclosporine, rather than tacrolimus given the drug-drug interaction between cyclosporine and ZEPATIER
  • Waitlisted for a multi-organ transplant
  • Evidence of end organ damage due to diabetes (e.g. retinopathy, nephropathy, ulcerations) and /or brittle diabetes mellitus (e.g. history of diabetic ketoacidosis) and/or uncontrolled diabetes as evidence by a HgbA1C of 7.5-8.5.
  • Chronic bronchitis, chronic obstructive pulmonary disease, inability to stop smoking.
  • Hematologic: Significant coagulation abnormalities, bleeding diatheses.
  • Psychosocial: Profound neurocognitive impairment with absence of social support.
  • Active mental illness or psychosocial instability
  • Inadequate insurance or financial support for post-transplant care.
  • Evidence of drug, tobacco or alcohol abuse within the past six months and completion of recommended therapy/services or meets satisfied parameters as indicated by social work staff and/or consult team.
  • History of chronic non-compliance.
  • Amyloidosis (restricted to cardiac only, without evidence of extra cardiac involvement)
  • BMI ≥38
  • Active peptic ulcer disease.
  • Severe malnutrition.
  • Major chronic disabling illness (e.g. lupus, severe arthritis, neurologic diseases, previous stroke with profound residual).
  • Pulmonary infarction within the past 6 weeks
  • Severe pulmonary hypertension as evidenced by a fixed pulmonary vascular resistance of greater than 4 Wood units on appropriate medical therapy.
  • Patient refusal to receive blood products or transfusions during heart transplant surgery.
  • Severe chronic obstructive pulmonary disease
  • Current clinical sepsis.
  • Symptomatic or severe vascular disease.
  • Chronic Kidney Disease Stage IV, Glomerular Filtration Rate < 30
  • History of Mantle radiation.
  • Asymptomatic renal cell carcinoma <1 year from curative treatment.
  • Symptomatic renal cell carcinoma <5 years from curative treatment.
  • Prostate cancer <2 years from curative treatment.
  • Uterine or cervical cancer <2 years from curative treatment.
  • Any other cancer other than the above including malignant melanoma, < 5 years from treatment apart from other skin malignancies.

Donor Organ Selection Criteria:

General criteria (although there can be exceptions on a case-by-case basis)

  • Detectable HCV RNA
  • Genotype 1 or 4 HCV
  • Age <=55 years
  • No history of coronary artery disease
  • No congenital heart disease except a repaired atrial septal defect (ASD) provided the patient has normal right ventricular function
  • No history of arrhythmia (atrial fibrilation, atrial flutter or VT) except during resuscitation from fatal event.
  • No evidence of cirrhosis

Echocardiographic criteria:

  • Left ventricular ejection fraction (LVEF) >=50%
  • Normal right ventricular function
  • No left ventricular hypertrophy (LVH) - septal wall thickness <1 cm
  • No left ventricular hypertrophy (LVH)- posterior wall thickness <1 cm
  • No significant valvular heart disease - more than mild tricuspid regurgitation, more than mild mitral regurgitation, more than trace aortic regurgitation. No mitral or aortic stenosis.
  • No congenital heart disease - transposition of the great vessels, ventricular septal defect (VSD), ASD, and/or single ventricle (Fontan)

Right heart catheterization criteria:

  • Right atrial pressure <=10mmHg
  • Pulmonary capillary wedge pressure <=18mmHg
  • CI >=2.1 l/min/m2
  • Pulmonary hypertension is allowed if the patient has normal right ventricular function and a normal tricuspid valve

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Zepatier (grazoprevir 100mg and elbasvir 50 mg)
Drug: Zepatier
Zepatier (grazoprevir 100mg and elbasvir 50 mg once daily) is taken by mouth for 12 weeks unless a genetic variation is detected. In this case treatment with Zepatier will be extended to 16 weeks. Study subjects with treatment failure will be provided open-label Zepatier + sofosbuvir (sovaldi) 400mg + Ribavirin (generic), renally dosed based on creatinine clearance per the manufacturer guidelines.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Post-treatment Sustained Virologic Response (SVR)
Time Frame: Baseline to 24 weeks
The primary analysis will be based on a calculation of SVR rates (number of subjects with SVR; negative HCV RNA after completing Zepatier therapy) / (number of subjects treated with Zepatier post-heart transplantation)
Baseline to 24 weeks
Number of Severe Adverse Events (SAE) Attributable to HCV Therapy Post-heart Transplant
Time Frame: Baseline to 52 weeks
Baseline to 52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Pennsylvania

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Merck Sharp & Dohme LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Peter Reese, MD, MSCE, Perelman School of Medicine at the University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 16, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 10, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 27, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 8, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 10, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 22, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 18, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 826708

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

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.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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