Cytokine Filtration in Lung Transplantation - a Randomised, Controlled, Multicentre Clinical Trial (GLUSorb)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Lund University Hospital
- Enrollment
- 116
- Locations
- 1
- Primary Endpoint
- To determine whether cytokine reduction by cytokine filtration leads to improved oxygenation in patients undergoing lung transplantation.
Study Overview
Brief Summary
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.
Detailed Description
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Eligibility to undergo double lung transplantation at either trial site
Exclusion Criteria
- •Age <18 years
- •Previous organ transplantation
- •Presence of any conditions at the time of surgery that require immunosuppressive therapy. Immunosuppressive therapy is defined as:
- •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.
- •Non-consent
Arms & Interventions
Non-treated
No additional treatment in conjunction with lung transplantation
Treated
Treatment using the medical "cytokine adsorption" device in conjunction with lung transplantation
Intervention: Device: CytoSorb (Device)
Outcomes
Primary Outcomes
To determine whether cytokine reduction by cytokine filtration leads to improved oxygenation in patients undergoing lung transplantation.
Time Frame: First 72 hours after 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
Time Frame: 24 hours after lung transplantation
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 72 hours
Time Frame: 72 hours after lung transplantation
Oxygenation expressed as the PaO2/FiO2 ratio at 72 hours
To determine whether cytokine reduction by cytokine filtration leads to improved oxygenation in patients undergoing lung transplantation. Oxygenation at 48 hours
Time Frame: 48 hours after lung transplantation
Oxygenation expressed as the PaO2/FiO2 ratio at 48 hours
Secondary Outcomes
- To determine whether cytokine reduction by cytokine filtration improves arterial blood gas measures in patients undergoing lung transplantation(0-72 hours (0-3 days) after lung transplantation)
- To determine whether cytokine reduction by cytokine filtration improves Chest CT in patients undergoing lung transplantation(First 4 years)
- To determine whether cytokine reduction by cytokine filtration improves presence of any CLAD in patients undergoing lung transplantation(First 4 years)
- To determine whether cytokine reduction by cytokine filtration improves kidney function in patients undergoing lung transplantation(First 4 years)
- To determine whether cytokine reduction by cytokine filtration decreases mortality in patients undergoing lung transplantation(First 4 years)
- To determine whether cytokine reduction by cytokine filtration improves quality of life (QOL) in patients undergoing lung transplantation(First 4 years)
- To determine whether cytokine reduction by cytokine filtration decreases need for norepinephrine in patients undergoing lung transplantation(0-72 hours (0-3 days) after lung transplantation)
- 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(First 4 years)
- To determine whether cytokine reduction by cytokine filtration improves levels of plasma inflammatory markers (including cytokines) in patients undergoing lung transplantation.(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(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(0-72 hours (0-3 days) after lung transplantation)
- To determine whether cytokine reduction by cytokine filtration improves diffusion capacity of the lungs (DLCO) in patients undergoing lung transplantation(First 4 years)
- To determine whether cytokine reduction by cytokine filtration decreases lung infiltrates and oedema in patients undergoing lung transplantation(0-72 hours (0-3 days) after lung transplantation)
- To determine whether cytokine reduction by cytokine filtration improves occurrence of any acute rejection episodes in patients undergoing lung transplantation(First 4 years)
Investigators
Sandra Lindstedt
Professor
Lund University Hospital