Evaluating the Addition of Hemodiafiltration to EVLP - Impact on the Regeneration of Marginal Donor Lungs

NCT ID: NCT06082401

Last Updated: 2025-05-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-01
• Study Completion Date: 2025-12-31

Brief Summary

The primary objective of the study is the evaluation of the effect of hemodiafiltration during ex vivo lung perfusion in marginal donor lungs, and its feasibility. The hypothesis of this study is that this therapy could stabilize perfusate electrolyte composition, remove toxins and waste products, normalize pH levels and prevent edema formation, thereby reconditioning marginal donor lungs for transplantation.

The proposed pilot study addresses the unmet clinical needs in several aspects: a) for the first time a homeostatic device will be introduced in EVLP to reach stable perfusate composition; b) the proposed modification of the standard EVLP could lead to longer perfusion times, making elective transplantation possible and setting the base for possible ex vivo lung treatments; c) the ultimate effect of the proposed study is to increase organ availability through reconditioning of marginal donor lungs.

Conditions

Lung Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Group

EVLP + HDF

Group Type: EXPERIMENTAL

hemodiafiltration (HDF)

Intervention Type: DEVICE

Hemodiafiltration (HDF) is a variation of conventional HD. By the addition of a substitution solution, convection forces are significantly increased. This substitution solution is added to the blood and is completely removed again in the dialyzer. This increases the negative pressure on the dialysate side and the removal of toxins through convection. The substitution solution can be added in a pre-dilution (before the dialyzer) or post-dilution (after the dialyzer) manner. Pre-dilution is associated with longer run times, less filter clotting, but is also less effective in removing toxins. Post-dilution offers a better toxin clearance capacity, but is associated with an increased risk of filter clotting. Several studies have shown that HDF provides higher clearance rates for both small and middle molecule solutes. Moreover, effective cytokine removal has been shown in HDF both in acute and chronic renal disease patients.

Ex vivo lung perfusion (EVLP)

Intervention Type: DEVICE

Lung transplantation has become a standard treatment for patients suffering from end-stage lung diseases. One of the major obstacles in the modern transplant era is the fact that the need for organs by far exceeds availability. This leads to growing waiting lists with mortality rates ranging between 10-30%. On the other hand, up to 80% of offered lungs from brain dead donors are rejected because they do not meet predefined donor selection criteria.

Recently, ex vivo lung perfusion (EVLP) has become available as a tool to expand the donor pool. Based on experimental work by Stig Steen, the Toronto lung transplant group developed an EVLP system with the purpose to evaluate lungs with uncertain quality. Consequently, Aigner et al. have expanded the indications for EVLP by showing that primarily unacceptable donor lungs can be reconditioned and then become suitable for transplantation. This concept of organ repair by EVLP has recently been highlighted by a number of publications.

Control Group

EVLP

Group Type: ACTIVE_COMPARATOR

Ex vivo lung perfusion (EVLP)

Intervention Type: DEVICE

Lung transplantation has become a standard treatment for patients suffering from end-stage lung diseases. One of the major obstacles in the modern transplant era is the fact that the need for organs by far exceeds availability. This leads to growing waiting lists with mortality rates ranging between 10-30%. On the other hand, up to 80% of offered lungs from brain dead donors are rejected because they do not meet predefined donor selection criteria.

Recently, ex vivo lung perfusion (EVLP) has become available as a tool to expand the donor pool. Based on experimental work by Stig Steen, the Toronto lung transplant group developed an EVLP system with the purpose to evaluate lungs with uncertain quality. Consequently, Aigner et al. have expanded the indications for EVLP by showing that primarily unacceptable donor lungs can be reconditioned and then become suitable for transplantation. This concept of organ repair by EVLP has recently been highlighted by a number of publications.

Interventions

hemodiafiltration (HDF)

Hemodiafiltration (HDF) is a variation of conventional HD. By the addition of a substitution solution, convection forces are significantly increased. This substitution solution is added to the blood and is completely removed again in the dialyzer. This increases the negative pressure on the dialysate side and the removal of toxins through convection. The substitution solution can be added in a pre-dilution (before the dialyzer) or post-dilution (after the dialyzer) manner. Pre-dilution is associated with longer run times, less filter clotting, but is also less effective in removing toxins. Post-dilution offers a better toxin clearance capacity, but is associated with an increased risk of filter clotting. Several studies have shown that HDF provides higher clearance rates for both small and middle molecule solutes. Moreover, effective cytokine removal has been shown in HDF both in acute and chronic renal disease patients.

Intervention Type: DEVICE

Ex vivo lung perfusion (EVLP)

Lung transplantation has become a standard treatment for patients suffering from end-stage lung diseases. One of the major obstacles in the modern transplant era is the fact that the need for organs by far exceeds availability. This leads to growing waiting lists with mortality rates ranging between 10-30%. On the other hand, up to 80% of offered lungs from brain dead donors are rejected because they do not meet predefined donor selection criteria.

Recently, ex vivo lung perfusion (EVLP) has become available as a tool to expand the donor pool. Based on experimental work by Stig Steen, the Toronto lung transplant group developed an EVLP system with the purpose to evaluate lungs with uncertain quality. Consequently, Aigner et al. have expanded the indications for EVLP by showing that primarily unacceptable donor lungs can be reconditioned and then become suitable for transplantation. This concept of organ repair by EVLP has recently been highlighted by a number of publications.

Intervention Type: DEVICE

Other Intervention Names

device: multiFiltrate Ci-Ca(R) (by Fresenius); device: XPS (TM) (by XVIVO)

Eligibility Criteria

Inclusion Criteria

• Marginal donor lungs according to the ISHLT criteria (18)

• PaO2/FiO2 ratio < 400 (with FiO2=1.0 and PEEP=5-8cmH2O)
• Donor age ≥ 55 years
• Smoking history ≥ 20 pack-years
• Infiltrates in chest radiograph
• Significant secretions in bronchoscopy
• Organisms on sputum gram stain
• Donor age > 18 years

Exclusion Criteria

For donor organs:

• Bilateral consolidations in donor lungs
• Lungs from donors with chest trauma
• Lungs from drowned donors

For patients receiving lung transplantation:

• Inclusions in other interventional studies
• Patients on the intensive care unit (ICU) prior to transplantation, with mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) support
• Re-transplantations

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

XVIVO Perfusion

INDUSTRY

Sponsor Role: collaborator

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Alberto Benazzo

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alberto Benazzo, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

Medical University of Vienna

Vienna, , Austria

Site Status: RECRUITING

Countries

Austria

Central Contacts

Panja M Boehm, MD

Role: CONTACT

panja.boehm@meduniwien.ac.at

004314040056440

Alberto Benazzo, MD

Role: CONTACT

alberto.benazzo@meduniwien.ac.at

004314040056440

Facility Contacts

Panja M Boehm, MD

Role: primary

panja.boehm@meduniwien.ac.at

004314040056400

Alberto Benazzo, MD

Role: backup

alberto.benazzo@meduniwien.ac.at

004314040056440

Other Identifiers

FILONEX

Identifier Type: -

Identifier Source: org_study_id