Combined Light, ExVivo, and Antivirals for Recipients of Lungs From HBV Donors

Phase 4RecruitingNCT07189377

University Health Network, Toronto20 enrolled

Overview

The aim of the study is to show that transplantation of lungs from Hepatitis B-infected donors is safe when using EVLP with UV light inactivation plus antivirals

The success of transplantation is significantly hindered by the lack of sufficient available donors. Many potential donor organs are not fully utilized in clinical transplantation because donors have chronic viral infections. Currently, donors with chronic hepatitis B virus (HBV) infection are utilized by typically providing nucleoside analogues such as entecavir or lamivudine plus/minus several doses of HBIG. The entecavir or lamivudine are typically given either life-long in liver transplants or for 1 year in non-liver transplants. Donors with chronic HBV infection are Core Antibody positive (HBcAb +ve). These donors carry chronic virus but may be NAT positive or NAT negative. HBcAb+ve donors are routinely used, but NAT positive donors are typically not used. The Toronto lung transplant program commonly applies Ex Vivo Lung Perfusion (EVLP) to organs. This allows for treatment of organs prior to transplantation. The investigators have shown that UV light administered on the EVLP circuit can substantially decrease the amount of infectious virus. Such a strategy was previously employed with hepatitis C virus. The aim of the study is to show that transplantation of organs from HBV NAT+ve donors is safe with the use of UV light treatment on EVLP combined with post-transplant antivirals for the recipient (HBIG and entecavir). The investigators hypothesize that rates of HBV transmission to recipients will be prevented by the use of this approach and any HBV transmission that does occur will be readily treatable. This will be a small pilot study to determine the feasibility of this approach. If successful, the knowledge from this study can have an important impact on patients awaiting lung transplantation by providing a novel strategy for the use of HBV-positive organ donors, simplified through a shorter course of approved antivirals.

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Hepatitis B Virus (HBV)Lung Transplant Recipient

Interventions

EntecavirDRUG

Recipients will receive 1mg administered orally, beginning pre-transplant as soon as the patient arrives to the hospital for surgery, and then 1mg post-operatively administered orally or via nasogastric tube once daily for 28 days.

HBIGBIOLOGICAL

Recipients will receive 4500 IU intravenously pre-transplant and then at day 3 and 7 post-transplant (3 doses total).

EVLP UV Light TreatmentDEVICE

UV light therapy will be administered to the organ during EVLP prior to transplantation. For minimum 2 hours, maximum 6 hours (duration determined by time clinically required for EVLP based on standard clinical assessment of lung).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Donor Inclusion Criteria * Donor lung suitable for transplantation * HBV SAg positive and/or HBV NAT+ donor Donor Exclusion Criteria * HIV positive * HTLV 1/2 positive; * Any medical issues in the donor that would normally clinically exclude the donor (e.g. history of cancer, evidence of organ dysfunction, etc). Recipient inclusion Criteria: * Recipients eligible and listed for lung transplant * HBV NAT negative * Provides written informed consent * Has received at least 3 prior doses of Hepatitis B vaccine or anti-HBs\>=10 IU/mL * Patients with other co-morbid conditions (such as diabetes, autoimmune disease, renal dysfunction) will remain eligible provided they are otherwise medically suitable for transplantation. The exception to this will be patients with significant liver disease as outlined below. Recipient exclusion Criteria: * Chronic liver disease with \> stage 2 fibrosis * Participating in another interventional clinical trial * Recipient listed for combined transplant (e.g., heart-lung, lung-liver) * Known allergy or contraindication to any of the antiviral medications * Hepatitis B surface antigen (HBsAg) or Hepatitis B core Ab positive pre-transplant (indicates already HBV infected). * HIV positive * Patients with a low level of serum IgA pre-transplant (this may be a risk factor for sensitivity reaction to HBIG).

Locations (1)

University Health Network, Toronto General Hospital

Toronto, Ontario, Canada

RECRUITING

Outcomes

Primary Outcomes

Safety of transplantation using HBV positive donors reflected by negative HBV NAT at 6 months post-transplant

Participant blood samples will be taken at days 3 and 7, then weekly for the first 4 weeks, then every two weeks until 12 weeks post-transplant, then at month 6 after transplantation. Blood samples will be tested for HBV DNA via Nucleic Acid Amplification.

Time frame: At 6 months post-transplant

Secondary Outcomes

Incidence of any HBV donor to recipient transmission

Time frame: From enrollment until 2 years post-transplant

Correlation between donor viremia level, and recipient infection

Time frame: From enrollment until up to 2 years post-transplant

Interval of time from transplantation to viremia development

Time frame: From enrollment until 2 years post-transplant

HBV suppression rates after treatment for infected patients

Time frame: From time of infection until end of treatment or up to 2 years post-transplant

Adverse reactions to antiviral therapy

Time frame: From enrollment until 2 years post-transplant

Incidence of acute liver dysfunction for infected patients

Time frame: From enrollment until 2 years post-transplant

In-hospital mortality

Time frame: From hospital admission until date of discharge or date of death from any cause, whichever comes first, assessed up to 2 years

1-year graft and patient survival

Central Contacts

Atul Humar, MD, FRCPC

CONTACT

416-340-4241 atul.humar@uhn.ca

Data from ClinicalTrials.gov

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