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

Evaluating the Addition of Hemodiafiltration to Ex-vivo Lung Perfusion - Impact on the Regeneration of Marginal Donor Lungs: a Prospective Randomized Pilot Study

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.

Study Overview

• Status: Recruiting
• Conditions: Lung Diseases
• Intervention / Treatment: Device: hemodiafiltration (HDF); Device: Ex vivo lung perfusion (EVLP)

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Panja M Boehm, MD; Phone Number: 004314040056440; Email: panja.boehm@meduniwien.ac.at
• Study Contact Backup: Name: Alberto Benazzo, MD; Phone Number: 004314040056440; Email: alberto.benazzo@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Alberto Benazzo, MD; Phone Number: 004314040056440; Email: alberto.benazzo@meduniwien.ac.at
    • Contact: Panja M Boehm, MD; Phone Number: 004314040056400; Email: panja.boehm@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group; EVLP + HDF	Device: 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.; Other Names: device: multiFiltrate Ci-Ca(R) (by Fresenius); 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.; Other Names: device: XPS (TM) (by XVIVO)
Active Comparator: Control Group; EVLP	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.; Other Names: device: XPS (TM) (by XVIVO)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
suitability for transplantation of the lungs after 6 hours of EVLP with HDF		6 hours
PGD grade 3 at 72 hours after transplantation	for all transplanted organs	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
survival	survival assessed at 12 and 24 months	months
Length of mechanical ventilation		up to 100 days
length of ICU stay		up to 100 days
length of hospital stay		up to 200 days
lung function parameters (MEF50)	1, 3, 6, 12 and 24 months after transplantation	24 months

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Collaborators: XVIVO Perfusion
• Investigators: Principal Investigator: Alberto Benazzo, MD, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: January 4, 2023
• First Submitted That Met QC Criteria: October 9, 2023
• First Posted (Actual): October 13, 2023

Study Record Updates

• Last Update Posted (Actual): May 14, 2025
• Last Update Submitted That Met QC Criteria: May 11, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases
• Other Study ID Numbers: FILONEX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No