• June 17, 2019

    Innovative heart transplant research using hepatitis C-positive donors

It all started with one very sick patient. Transplant cardiologists Shelley Hall, MD, and Robert Gottlieb, MD, PhD, and cardiothoracic surgeon Gonzo Gonzalez-Stawinski, MD, with Baylor University Medical Center, part of Baylor Scott & White Health, faced a difficult situation. A heart transplant was needed for a patient with biventricular heart failure and multiple comorbidities, but her condition made her a poor candidate for bridging mechanical support therapy, like a ventricular assist device (VAD). Even though the Heart Transplant Program in the Baylor Annette C. and Harold C. Simmons Transplant Institute at Baylor University Medical Center is nationally recognized for short donor organ wait times, it was not clear if a suitable donor heart would appear before the patient succumbed to the disease.

Given the dire situation, the team of physicians opened a dialogue with the patient about transplanting the first available heart, regardless of whether it was from a donor that could transmit the hepatitis C virus (HCV), followed by treatment with direct-acting antivirals if she became infected. With recent innovations in antiviral therapies, it was now possible to deliver curative HCV treatment that was theoretically compatible with the immunosuppressive transplant procedure. Within hours of indicating on the national waitlist that a heart with HCV would be evaluated for transplant, a suitable heart became available, and the transplant was a success. This clinical success planted a seed that has grown into the TROJAN-C multicenter phase 2 clinical trial, which is led by the team at Baylor University Medical Center and sponsored by Baylor Scott & White Research Institute (BSWRI).

This first patient underwent testing for HCV, which detected the virus by day five after transplant. Treatment with sofosbuvir/velpatasvir, starting on day 13, promptly suppressed the viral titer to below the limit of detection by day 23, and 12 weeks after therapy was completed, she was deemed cured of hepatitis C. The patient had no need for further hospitalization after her transplant. This test case was an essential proof-of-principle, but more work was needed to determine the safety in a larger population.

Dr. Hall, National Study Chair for the TROJAN-C trial, described the early phases of study development, “We had these great new antiviral drugs, but nobody was talking about using them for heart transplants. I organized a meeting among the other leaders of transplant centers around the country to talk about developing procedures for using HCV-positive donor heart organs as a research priority.” At the same time, a consensus statement (on which Dr. Hall is a co-author) from the American Society of Transplantation and the American Society of Transplant Surgeons in 2017 described an urgent need for prospective research on the risks and benefits of transplanting HCV-positive donor organs.

The researchers then engaged BSWRI to navigate the organizational and regulatory challenges involved in bringing such a groundbreaking trial to fruition. BSWRI is a consolidated infrastructure resource to facilitate research and development across all Baylor Scott & White Health, the largest not-for-profit healthcare system in Texas. Regulatory specialists in the Clinical Trials Office provided in-depth consultation to coordinate with the FDA and develop a clinical protocol. According to Dr. Gottlieb, who is the Principal Investigator for the Baylor University Medical Center site of the TROJAN-C trial, “We are very aware that we are knowingly transmitting a virus to save a life. This is a special circumstance, and we were able to have very thoughtful discussions with BSWRI and our Institutional Review Board about how to collect more data to see if this is a safe strategy.”

Funding was obtained from both the Baylor Scott & White Dallas Foundation and the American Society of Transplant Surgeons, via their Expanding Organ Donation and Transplantation grant program. BSWRI provides comprehensive support for the management of grants and contracts, as well as services in clinical trial recruitment planning, study coordination, clinical laboratory analysis, training and communication among trial sites. The TROJAN-C trial is one of more than 600 active or actively enrolling Investigator-Initiated studies BSWRI is currently supporting, in addition to its larger portfolio of sponsored clinical trials across nearly 50 specialty areas.

Together, the team coordinated the establishment of three centers: Cedars-Sinai Medical Center in California, Duke University Medical Center in North Carolina and Baylor University Medical Center in Texas, which is the lead site. The TROJAN-C study intends to recruit patients to receive the next available donor heart regardless of HCV status, and it will enroll up to 20 patients who receive an HCV-positive heart. Patients with PCR-confirmed HCV viremia will receive sofosbuvir/velpatasvir for 12 weeks with close surveillance, with follow-up evaluation at one year.

The Baylor University Medical Center team described their experience with the landmark HCV-positive donor heart recipient in the Journal of Cardiac Failure in 2017. More information about the TROJAN-C trial can be found online.