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

Lung Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06082401
• Other study ID #: FILONEX
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: October 2023
• Source: Medical University of Vienna
• Contact: Panja M Boehm, MD
• Phone: 004314040056440
• Email: panja.boehm[@]meduniwien.ac.at
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Diseases

Intervention

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.
• 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.

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of Vienna	XVIVO Perfusion

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	suitability for transplantation of the lungs after 6 hours of EVLP with HDF		6 hours
Primary	PGD grade 3 at 72 hours after transplantation	for all transplanted organs	72 hours
Secondary	survival	survival assessed at 12 and 24 months	months
Secondary	Length of mechanical ventilation		up to 100 days
Secondary	length of ICU stay		up to 100 days
Secondary	length of hospital stay		up to 200 days
Secondary	lung function parameters (MEF50)	1, 3, 6, 12 and 24 months after transplantation	24 months