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Expanding the Pool in Orthotopic Heart Transplantation

Primary Purpose

Hepatitis C, Heart Transplant, Cardiac Transplant

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

sofosbuvir/velpatasvir

About this trial

This is an interventional other trial for Hepatitis C

Eligibility Criteria

18 Years - 71 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria (recipients):

End stage heart failure
Age ≥ 18 and <71 years
Listed heart transplant at UPMC
Have panel reactive antibody level of <98%
No obvious contraindication to liver transplant
Able to travel to UPMC for routine post-transplant visits and study visits for a minimum of 12 months after transplantation
Able to provide informed consent
Be willing to use a contraceptive method for a year after transplant

Inclusion criteria (donors):

HCV antibody positive
HCV NAT negative or positive
Acceptable cardiac function for donation

Exclusion criteria (recipients):

HIV positive
HCVAb or HCV RNA positive
Presence of behavioral risk factors for contracting HCV. These behavioral risk factors are current injection drug use, current intranasal illicit drug use, current percutaneous/parenteral exposures in an unregulated setting.
Hepatitis B surface antigen positive
History of liver cirrhosis
Persistently elevated liver transaminases, defined as ALT/AST at least 3 times the upper limit of normal for a minimum of 3 consecutive months
Waitlisted for a multi-organ transplant
Pregnant women
Known allergy to sofosbuvir/velpatasvir
Any condition, psychiatric or physical, that in the opinion of the investigator would make it unsafe to proceed with transplantation or interfere with the ability of the subject to participate in the study
Ongoing therapy with amiodarone for atrial or ventricular arrhythmia Prescribed use of Amiodarone

Exclusion criteria (donors):

Confirmed HIV positive (positive HIV-1 antibody, positive HIV-2 antibody, positive p24 antigen and/or positive HIV NAT)
Confirmed HBV positive (positive hepatitis B surface antigen and/or HBV NAT) Known ongoing therapy for HCV

Sites / Locations

UPMC

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

HCV seropositive non-viremic (HCV Ab+/NAT-) donor

HCV seropositive viremic (HCV Ab+/NAT+) donor

Arm Description

HCV seropositive non-viremic (HCV Ab+/NAT-) donor hearts to HCV seronegative recipients. Heart recipients will be monitored for HCV for one year following transplant. When HCV RNA is detected, the transmission-triggered treatment phase will be initiated. Recipients will be treated with 12-week oral course of sofosbuvir/velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg). Intervention: Drug: sofosbuvir/velpatasvir

HCV seropositive viremic (HCV Ab+/NAT+) donor hearts to HCV seronegative recipients. Starting post-operative day 1, heart recipients will be treated with 12-week oral course of sofosbuvir/velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg). Intervention: Drug: sofosbuvir/velpatasvir

Outcomes

Primary Outcome Measures

Adverse Events

Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in patients in each experimental group

HCV free at 1 year

Proportion of participants in each experimental group who are free of HCV at 1 year following transplantation

Secondary Outcome Measures

Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients

Incidence of allograft rejection

Incidence of graft loss

All-cause mortality

Waitlist time after enrollment

Full Information

NCT ID

NCT03222531

First Posted

July 5, 2017

Last Updated

September 6, 2023

Sponsor

Mary E. Keebler, MD

1. Study Identification

Unique Protocol Identification Number

NCT03222531

Brief Title

Expanding the Pool in Orthotopic Heart Transplantation

Official Title

Expanding the Pool in Orthotopic Heart Transplantation: The Use of Hepatitis C Positive Donor Hearts in Hepatitis C Negative Recipients

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 1, 2017 (Actual)

Primary Completion Date

December 1, 2023 (Anticipated)

Study Completion Date

December 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Mary E. Keebler, MD

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is an open-label, pilot trial to test the safety and efficacy of transplantation of hearts from HCV seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic (HCV Ab+/NAT+) donors to HCV seronegative recipients on the heart transplant waitlist. Treatment and prophylaxis will be administered, using a transmission-triggered approach for the first scenario (HCV Ab+/NAT- donors, arm 1) and a prophylaxis approach for the later scenario (HCV Ab+/NAT+ donors, arm 2).

Detailed Description

This is a prospective, single center, pilot, open-label study of transplantation of hearts of HCVAb+ donors to HCVAb- recipients with subsequent therapy with sofosbuvir/velpatasvir (Epclusa®). Recipients of a heart from HCVAb+/NAT- donors is ARM 1 or the transmission-triggered arm of the study. In this arm, the study will monitor transmission of HCV by measuring HCV RNA in heart transplant recipients. If HCV RNA is detected, indicating transmission of HCV, recipients will be treated with sofosbuvir/velpatasvir (Epclusa®) for 12 weeks. Virological response will be assessed at 4 weeks, end of treatment and 12 weeks after completion of therapy. Recipients of a heart from HCVAb+/NAT+ donors will be in ARM 2 or the prophylaxis arm of the study. In this arm, patients will be started on a 12-week course of sofosbuvir/velpatasvir (Epclusa®) on post-operative day 1 and will undergo close monitoring of HCV RNA for evidence of transmission as well as monitoring of adverse events from therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis C, Heart Transplant, Cardiac Transplant

7. Study Design

Primary Purpose

Other

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

HCV seropositive non-viremic (HCV Ab+/NAT-) donor

Arm Type

Experimental

Arm Description

Arm Title

HCV seropositive viremic (HCV Ab+/NAT+) donor

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

sofosbuvir/velpatasvir

Other Intervention Name(s)

Epclusa

Intervention Description

Drug: sofobuvir/velpatasvir

Primary Outcome Measure Information:

Title

Adverse Events

Description

Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in patients in each experimental group

Time Frame

5 years

Title

HCV free at 1 year

Description

Proportion of participants in each experimental group who are free of HCV at 1 year following transplantation

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients

Time Frame

5 years

Title

Incidence of allograft rejection

Time Frame

5 years

Title

Incidence of graft loss

Time Frame

5 years

Title

All-cause mortality

Time Frame

5 years

Title

Waitlist time after enrollment

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

71 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria (recipients): End stage heart failure Age ≥ 18 and <71 years Listed heart transplant at UPMC Have panel reactive antibody level of <98% No obvious contraindication to liver transplant Able to travel to UPMC for routine post-transplant visits and study visits for a minimum of 12 months after transplantation Able to provide informed consent Be willing to use a contraceptive method for a year after transplant Inclusion criteria (donors): HCV antibody positive HCV NAT negative or positive Acceptable cardiac function for donation Exclusion criteria (recipients): HIV positive HCVAb or HCV RNA positive Presence of behavioral risk factors for contracting HCV. These behavioral risk factors are current injection drug use, current intranasal illicit drug use, current percutaneous/parenteral exposures in an unregulated setting. Hepatitis B surface antigen positive History of liver cirrhosis Persistently elevated liver transaminases, defined as ALT/AST at least 3 times the upper limit of normal for a minimum of 3 consecutive months Waitlisted for a multi-organ transplant Pregnant women Known allergy to sofosbuvir/velpatasvir Any condition, psychiatric or physical, that in the opinion of the investigator would make it unsafe to proceed with transplantation or interfere with the ability of the subject to participate in the study Ongoing therapy with amiodarone for atrial or ventricular arrhythmia Prescribed use of Amiodarone Exclusion criteria (donors): Confirmed HIV positive (positive HIV-1 antibody, positive HIV-2 antibody, positive p24 antigen and/or positive HIV NAT) Confirmed HBV positive (positive hepatitis B surface antigen and/or HBV NAT) Known ongoing therapy for HCV

Facility Information:

Facility Name

UPMC

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Expanding the Pool in Orthotopic Heart Transplantation

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