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.
Early intolerance to the newly transplanted lung starts at the time of transplantation and results in PGD driven by an intense inflammatory response. Cytokines play a critical role as signaling molecules that initiate, amplify, and maintain inflammatory responses both locally and systemically. The use of cytokine filtration devices to target middle- and low-molecular weight molecules has been shown to reduce levels of a diverse number of cytokines. These results have been demonstrated in the in vitro reduction of pathogen-associated molecular pattern molecules (PAMPS) and damage associated molecular patterns (DAMPS) as well as in in vivo studies involving orthotopic heart transplantation and kidney transplantation. Cytokine adsorption has been used successfully in clinical applications to both heart and kidney transplantation. The present study is a randomized controlled study which aims to collect preliminary data on the efficacy of a medical device through the comparison of patients undergoing LTx with and without cytokine adsorption.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
116
Medical device used hemoperfusion and cytokine adsorption in conjunction with lung transplantation.
Sandra Lindstedt
Lund, Skåne County, Sweden
RECRUITINGTo 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.
Time frame: First 72 hours after lung transplantation
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
Time frame: 24 hours after lung transplantation
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
Time frame: 48 hours after lung transplantation
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
Time frame: 72 hours after lung transplantation
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
Time frame: 0-72 hours (0-3 days) after lung 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
Time frame: 0-72 hours (0-3 days) after lung 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
Time frame: 0-72 hours (0-3 days) after lung transplantation
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
Time frame: 0-72 hours (0-3 days) after lung transplantation
To determine whether cytokine reduction by cytokine filtration decreases incidence of primary graft dysfunction (PGD) in patients undergoing lung transplantation
Presence of any grade of PGD on day 1, 2, and 3 after transplantation, as a measure of lung function
Time frame: 0-72 hours (0-3 days) after lung transplantation
To determine whether cytokine reduction by cytokine filtration decreases need for norepinephrine in patients undergoing lung transplantation
Total dose of norepinephrine administered in the first 72 h
Time frame: 0-72 hours (0-3 days) after lung transplantation
To determine whether cytokine reduction by cytokine filtration decreases mortality in patients undergoing lung transplantation
Mortality up to 48 months after transplantation
Time frame: First 4 years
To determine whether cytokine reduction by cytokine filtration improves diffusion capacity of the lungs (DLCO) in patients undergoing lung transplantation
Lung diffusion capacity, measured by carbon monoxide (CO) diffusion, at 6, 12, 24, and 48 months after transplantation, as a measure of lung function
Time frame: First 4 years
To determine whether cytokine reduction by cytokine filtration improves forced expiratory volume (FEV1), forced vital capacity (FVC), and total lung capacity in patients undergoing lung transplantation
Forced expiratory volume (FEV1), forced vital capacity (FVC), and total lung capacity (TLC) measured by spirometry at 1, 3, 6, 12, 24 and 48 months after transplantation, as a measure of lung function
Time frame: First 4 years
To determine whether cytokine reduction by cytokine filtration improves occurrence of any acute rejection episodes in patients undergoing lung transplantation
Occurrence of any acute rejection episodes (clinically treated and/or biopsy verified) up to 48 months after transplantation, as a measure of lung function
Time frame: First 4 years
To determine whether cytokine reduction by cytokine filtration improves Chest CT in patients undergoing lung transplantation
Chest CT findings at 1, 3, 6, 12, 24, 36 and 48 months after transplantation
Time frame: First 4 years
To determine whether cytokine reduction by cytokine filtration improves presence of any CLAD in patients undergoing lung transplantation
Presence of any CLAD and CLAD subtypes up to 48 months after transplantation, as a measure of lung function
Time frame: First 4 years
To determine whether cytokine reduction by cytokine filtration improves kidney function in patients undergoing lung transplantation
Kidney function evaluated by measurement of serum creatinine levels; calculated glomerular filtration rate (GFR); and need for renal replacement therapy on day 1, 2, and 3 and at 1, 3, 6, 9, 12, 24, and 48 months after transplantation; urea levels on day 1, 2, and 3 after transplantation; and iohexol clearance at 3, 6, 9, 12, 24, 36, and 48 months after transplantation
Time frame: First 4 years
To determine whether cytokine reduction by cytokine filtration improves quality of life (QOL) in patients undergoing lung transplantation
QOL evaluated by the 36-Item Short Form Health Survey (SF-36) at 24 and 48 months after transplantation
Time frame: First 4 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.