Clinical trial NCT03222531: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Hepatitis C
Heart Transplant
Cardiac Transplant
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2017-07-19
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 71
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Adverse Events
timeFrame: 5 years
measure: HCV free at 1 year
timeFrame: 1 year
Secondary outcomes:
measure: Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients
timeFrame: 5 years
measure: Incidence of allograft rejection
timeFrame: 5 years
measure: Incidence of graft loss
timeFrame: 5 years
measure: All-cause mortality
timeFrame: 5 years
measure: Waitlist time after enrollment
timeFrame: 5 years
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
Study officials:
References: