Using hepatitis C–positive donor hearts for hepatitis C–negative recipients treated with Epclusa

Transplant of Redeemed Organs by Judicious Administration of New Direct-Acting Antivirals for Hepatitis-C Heart Recipients

This test will see if giving Epclusa to hepatitis C–negative heart transplant recipients prevents hepatitis C infection and allows safe use of hearts from HCV-positive donors.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years to 90 Years
• Sex: All
• Sponsor: Baylor Research Institute (other)
• Locations: 3 sites (Los Angeles, California and 2 other locations)
• Trial ID: NCT03383419 on ClinicalTrials.gov

What this trial studies

This Phase II, multicenter, open-label protocol enrolls adults listed for isolated orthotopic heart transplant who are HCV seronegative or have documented prior clearance. Consented participants who accept an HCV-NAT–positive donor heart are closely monitored with serial HCV PCR testing and donor HCV NAT/genotype analysis. If recipients develop confirmed HCV viremia post-transplant, they receive a 12-week course of sofosbuvir 400 mg/velpatasvir 100 mg (Epclusa) provided by the sponsor. Patients lacking hepatitis B immunity are encouraged to begin hepatitis B vaccination and all participants are followed through the post-transplant period per protocol.

Who should consider this trial

Good fit: Adults (≥18) listed for isolated orthotopic heart transplant who are HCV seronegative (or previously cleared infection with documented negative PCRs) and willing to accept an HCV-positive donor heart are ideal candidates.

Not a fit: Patients listed for combined organ transplants, those with active or uncured HCV viremia, cirrhosis, active hepatitis B infection, or other listed exclusion criteria are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could expand the donor heart pool and let more patients get transplants sooner while preventing chronic HCV infection with antiviral therapy.

How similar studies have performed: Similar protocols using direct-acting antivirals to permit transplantation of HCV-positive donor kidneys and livers into HCV-negative recipients have shown high cure rates, and this trial applies that approach to heart transplantation.

Eligibility criteria

Inclusion Criteria:

1. Willing and capable of providing written informed consent
2. Age ≥ 18 years
3. Listed for isolated orthotopic heart transplant
4. HCV seronegative (or, if HCV seropositive, then subject must be PCR negative on at least 2 draws consistent with a spontaneously cleared or fully-treated and cleared prior infection; in this case last anti-HCV antiviral dose must be ≥12 weeks ago and 2 negative titers ≥12 weeks after completion of the antiviral regimen)

Exclusion Criteria:

1. Listed for combined organ transplant
2. Any of the following liver disease states, including:

   1. History of HCV viremia detectable by either HCV qualitative or quantitative PCR unless deemed cured (SVR-12),
   2. Hepatitis B surface Ag positive(unless clinically determined to be previously negative and acutely positive due to vaccination with recombinant surface antigen) or detectable hepatitis B DNA,
   3. Cirrhosis, as indicated by liver biopsy,
   4. Portal hypertension as indicated by a hepatic venous pressure gradient \> 5 mm Hg and/or the presence of esophageal varices e.) ALT and AST \> 3x ULN unless adjudicated to be from a non-hepatic cardiac or skeletal muscle source,
3. History of prior solid organ transplant
4. Pregnant individuals
5. History of HIV infection
6. History of severe renal disease currently requiring dialysis. Chronic kidney disease with creatinine clearance \<30 ml/min/1.73m2 (by MDRD method) at screening or on last two consecutive measurements before acceptance of transplant organ offer
7. Patients who have undergone or who will undergo immune desensitization therapy
8. Prospective-positive cross-match or predicted positive cross-match
9. Patients unwilling to notify their sexual partner(s) of participation in this trial

Where this trial is running

Los Angeles, California and 2 other locations

• Cedars-Sinai Medical Center — Los Angeles, California, United States (RECRUITING)
• Duke University Medical Center — Durham, North Carolina, United States (ACTIVE_NOT_RECRUITING)
• Baylor University Medical Center — Dallas, Texas, United States (RECRUITING)

Study contacts

• Study coordinator: Aayla Jamil, MBBS MPH

Conditions: Heart Failure, Heart Failure, Heart Transplant