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

Study Overview
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Brief Summary
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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.

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

Conditions
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Lung Diseases

Intervention / Treatment
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* Device: hemodiafiltration (HDF)
* Device: Ex vivo lung perfusion (EVLP)


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>EVLP + HDF | Device: hemodiafiltration (HDF)<br>* 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.<br>* Other names: device: multiFiltrate Ci-Ca(R) (by Fresenius);Device: Ex vivo lung perfusion (EVLP)<br>* 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.<br>* Other names: device: XPS (TM) (by XVIVO);|
| Active Comparator: Control Group<br>EVLP | Device: Ex vivo lung perfusion (EVLP)<br>* 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.<br>* Other names: device: XPS (TM) (by XVIVO);|

What is the study measuring?
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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 |