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

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

Overview

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.

Interventions

• 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 associ
• 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 be

Primary outcome measures

• suitability for transplantation of the lungs after 6 hours of EVLP with HDF [Time frame: 6 hours]
• PGD grade 3 at 72 hours after transplantation [Time frame: 72 hours]

Secondary outcome measures (5)

• survival [Time frame: months]
• Length of mechanical ventilation [Time frame: up to 100 days]
• length of ICU stay [Time frame: up to 100 days]
• length of hospital stay [Time frame: up to 200 days]
• lung function parameters (MEF50) [Time frame: 24 months]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Austria · 1 center

• Medical University of Vienna — Vienna

Identifiers

NCT: NCT06082401 · FILONEX

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗