About this trial
Lung transplantation (LTx) remains the gold standard for treating patients with irreversible end-stage pulmonary disease. Of the major organs transplanted, survival in LTx recipients remains the lowest (mean 5 years). Despite improvements, primary graft dysfunction (PGD), as defined by respiratory insufficiency and edema up to 72 hours post LTx, remains the leading cause of early mortality and contributes to the development of chronic lung allograft dysfunction (CLAD) which is the leading cause of late mortality. PGD develops within the first 72 hours after LTx. The development of CLAD increases quickly with cumulative incidence of 40-80 % within the first 3-5 years. There is a general lack of efficient treatments for PGD and CLAD. Prevention of PGD is therefore of crucial importance and has a direct impact on survival.
The present study is a randomized controlled study which aims to compare patients undergoing LTx with and without the utilization of cytokine adsorption.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
None
Disqualifiers
Age <18 years
Previous organ transplantation
Cyclosporine, Tacrolimus, Everolimus, or Sirolimus, minimum 1 month of treatment prior to transplantation and active treatment at the time of transplantation.
Any form of antibody-based treatment that is known for having an immunomodulatory effect taken up to 1 week before transplantation.
Trial design
Parallel
Treatments tested in this trial
Device: CytoSorb
DeviceMedical device used hemoperfusion and cytokine adsorption in conjunction with lung transplantation.
Treatment groups
Trial outcomes
Primary outcomes
To determine whether cytokine reduction by cytokine filtration leads to improved oxygenation in patients undergoing lung transplantation.
Higest value of oxygenation expressed as the PaO2/FiO2 ratio.
To determine whether cytokine reduction by cytokine filtration leads to improved oxygenation in patients undergoing lung transplantation. Oxygenation at 24 hours
Oxygenation expressed as the PaO2/FiO2 ratio at 24 hours
To determine whether cytokine reduction by cytokine filtration leads to improved oxygenation in patients undergoing lung transplantation. Oxygenation at 48 hours
Oxygenation expressed as the PaO2/FiO2 ratio at 48 hours
To determine whether cytokine reduction by cytokine filtration leads to improved oxygenation in patients undergoing lung transplantation. Oxygenation at 72 hours
Oxygenation expressed as the PaO2/FiO2 ratio at 72 hours
Secondary outcomes
To determine whether cytokine reduction by cytokine filtration improves levels of plasma inflammatory markers (including cytokines) in patients undergoing lung transplantation.
Plasma levels of inflammatory markers: interleukin (IL)-10, IL-1β, soluble IL-2 receptor, IL-6, IL-8, and tumour necrosis factor (TNF)α before and immediately after transplantation and at 6, 12, 24, 48, and 72 hours after transplantation, and C-reactive protein (CRP) and white blood cells before and immediately after transplantation and at day 1, 2, and 3 after transplantation
To determine whether cytokine reduction by cytokine filtration decreases lung infiltrates and oedema in patients undergoing lung transplantation
Infiltrates and oedema measured by chest x-ray and/or CT scan of the thorax at day 1, 2, and 3 after transplantation
To determine whether cytokine reduction by cytokine filtration improves arterial blood gas measures in patients undergoing lung transplantation
Highest daily arterial blood gas measurements recorded on day 1, 2, and 3 after transplantation, as a measure of lung function
To determine whether cytokine reduction by cytokine filtration decreases severity of primary graft dysfunction (PGD) in patients undergoing lung transplantation
PGD severity as evaluated per standard clinical procedures using a rating scale from 0-3 on day 1, 2, and 3 after transplantation, as a measure of lung function
Other outcomes
Safety endpoints
Adverse events in the first 72 hours after transplantation. Thus, the aim of this clinical trial is to determine the efficacy of cytokine filtration in improving successful LTx rates, based on its effects on oxygenation ratio, pulmonary function, PGD, kidney function, CLAD, and survival. These outcomes will also be analysed on the molecular, and tissue levels to identify the mechanisms by which cytokine filtration promotes the acceptance of lung transplants. The primary outcome will be oxygenation ratio, defined as the highest PaO2/FiO2 (P/F) within 72 h after LTx.
Exploratory endpoints
Collection of a portion of routinely collected transplanted lung tissue by transbronchial biopsy and bronchoalveolar lavage fluid (at least at 1, 3 and 12 months, with additional timepoints if clinically indicated), collection of explanted recipient lung tissue, and collection of blood samples (at least before transplantation; immediately after transplantation; 6, 12, 24, 48, and 72 hours; 1 and 2 weeks; and 1, 3, 6, 9, 12, 24, 36, and 48 months after transplantation, with additional timepoints if clinically indicated) in a biobank for future exploratory analyses.
Sponsors and contacts
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