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

NCT ID: NCT07189377

Last Updated: 2025-11-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-24
• Study Completion Date: 2027-08-31

Brief Summary

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

Detailed Description

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.

Conditions

Hepatitis B Virus (HBV); Lung Transplant Recipient

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

UV Light + Short-course Entecavir/HBIG

Patients will receive lungs from HBV NAT+ donors, which will be treated with UV light therapy during ex-vivo perfusion. Patients will also receive Entecavir and HBIG prophylaxis in the immediate peri-operative period.

Group Type: EXPERIMENTAL

Entecavir

Intervention Type: DRUG

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.

HBIG

Intervention Type: BIOLOGICAL

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

EVLP UV Light Treatment

Intervention Type: DEVICE

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).

Interventions

Entecavir

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.

Intervention Type: DRUG

HBIG

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

Intervention Type: BIOLOGICAL

EVLP UV Light Treatment

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).

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Donor lung suitable for transplantation
• HBV SAg positive and/or HBV NAT+ donor

• 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.

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).

• 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Health Network, Toronto General Hospital

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Atul Humar, MD, FRCPC

Role: CONTACT

atul.humar@uhn.ca

416-340-4241

Facility Contacts

Ilona Bahinskaya, MSc, CCRP

Role: primary

Ilona.Bahinskaya@uhn.ca

416-340-4800 ext. 4328

Other Identifiers

24-6051

Identifier Type: -

Identifier Source: org_study_id