Utilization of Hepatitis B Virus NAT+ Donors for Hepatitis B Vaccinated Lung Transplant Candidates

• Status: Not yet recruiting
• Trial end date: 2032-08-01
• Target enrollment: 0
• Participant gender: All

Summary

The objective of this study is to determine the safety and efficacy of transplanting lungs from hepatitis B virus (HBV) nucleic acid test positive (NAT+) donors into HBV vaccinated HBV surface antibody positive (sAb+) lung transplant candidates, who will then be treated with Hepatitis B Immune Globulin (HBIG) and entecavir, tenofovir disoproxil, or tenofovir alafenamide.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pennsylvania
• Treatments: Antibodies; Entecavir; gamma-Globulins; Immunoglobulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin; Tenofovir

Criteria

Inclusion Criteria:

• Age 18-70 years

• Able to provide informed consent

• Willing and able to travel to the University of Pennsylvania for routine post-transplant study visits

• Pre-menopausal women must agree to use birth control in accordance with the Mycophenolate Risk Evaluation and Mitigation Strategy (REMS) following transplant

• 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 HBV transmission

• Appropriate HBV vaccine pre-transplant response, defined as HBV sAb ≥12.00 mIU/mL

Exclusion Criteria:

• Donor characteristics:

• Donation after circulatory death donor

• Hepatitis C Virus (HCV) NAT+

• PaO2/FiO2 <300 on FiO2 = 100% and PEEP=5

• Age >55 years

• Smoking history >20 pack years

• Transplant candidate characteristics:

• Age >70 years

• Any chronic liver disease (excluding non-alcoholic fatty liver disease (NAFLD)) associated with persistently elevated liver enzymes

• Significant fibrosis (≥F2 on Fibroscan or Fib4 ≥1.67 (for patients unable to complete Fibroscan and without liver disease risk factors))

• Inadequate insurance coverage of entecavir, tenofovir disoproxil, or tenofovir alafenamide

• Retransplant candidate

• Current use of extracorporeal membrane oxygenation (ECMO) or mechanical ventilation as a bridge to lung transplantation

• HIV infection

• Chronic kidney disease with estimated glomerular filtrate rate less than 50 ml/min/1.73 m2

• Small bowel dysmotility or plan for prolonged medications and/or nutrition via tube route in the post-transplant period

• Significant human leukocyte antibody (HLA) sensitization (Calculated Panel Reactive Antibody (CPRA) ≥60%)

• Planned or high likelihood of anti-thymocyte globulin induction immunosuppression or rituximab treatment

• Known hypercoagulable states including positive antiphospholipid antibodies with prior venous or arterial thromboembolic events or Factor V Leiden or Prothrombin mutations with or without prior venous or arterial thromboembolic events

• History of hypersensitivity or anaphylactic reaction to immune globulin or similar products

• Receiving or anticipated to receive drugs with significant entecavir or tenofovir interactions including phenytoin/fosphenytoin, oxcarbazepine, phenobarbital, primidone, rifabutin, and rifampin