Recruiting NCT05526950

Cytokine Filtration in Lung Transplantation: A Swedish National Study (GLUSorb)

No phase Interventional Lung Transplant Failure Lung Transplant; Complications

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Device: CytoSorb.
Who it may be relevant to: Registry conditions: Lung Transplant Failure, Lung Transplant; Complications. Basic parameters: 18 years — 80 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: Sweden
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

Cytokine Filtration in Lung Transplantation - a Randomised, Controlled, Multicentre Clinical Trial (GLUSorb)

Overview

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.

Interventions

Device Device: CytoSorb
Medical device used hemoperfusion and cytokine adsorption in conjunction with lung transplantation.

Primary outcome measures

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]
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]
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]
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]

Secondary outcome measures (12)

To determine whether cytokine reduction by cytokine filtration improves levels of plasma inflammatory markers (including cytokines) in patients undergoing lung 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 [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 [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 [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 [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 [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 [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 [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 [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 [Time frame: First 4 years]
To determine whether cytokine reduction by cytokine filtration improves Chest CT in patients undergoing lung transplantation [Time frame: First 4 years]
To determine whether cytokine reduction by cytokine filtration improves presence of any CLAD in patients undergoing lung transplantation [Time frame: First 4 years]

Eligibility criteria

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

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

Sweden · 1 center

Sandra Lindstedt — Lund

Publications

Ghaidan H, Stenlo M, Niroomand A, Mittendorfer M, Hirdman G, Gvazava N, Edstrom D, Silva IAN, Broberg E, Hallgren O, Olm F, Wagner DE, Pierre L, Hyllen S, Lindstedt S. Reduction of primary graft dysfunction using cytokine adsorption during organ preservation and after lung transplantation. Nat Commun. 2022 Jul 26;13(1):4173. doi: 10.1038/s41467-022-31811-5. PMID 35882835
Niroomand A, Qvarnstrom S, Stenlo M, Malmsjo M, Ingemansson R, Hyllen S, Lindstedt S. The role of mechanical ventilation in primary graft dysfunction in the postoperative lung transplant recipient: A single center study and literature review. Acta Anaesthesiol Scand. 2022 Apr;66(4):483-496. doi: 10.1111/aas.14025. Epub 2022 Jan 27. PMID 35014027
Niroomand A, Hirdman G, Olm F, Lindstedt S. Current Status and Future Perspectives on Machine Perfusion: A Treatment Platform to Restore and Regenerate Injured Lungs Using Cell and Cytokine Adsorption Therapy. Cells. 2021 Dec 29;11(1):91. doi: 10.3390/cells11010091. PMID 35011653
Lindstedt S, Niroomand A, Mittendorfer M, Hirdman G, Hyllen S, Pierre L, Olm F. Nothing but NETs: Cytokine adsorption correlates with lower circulating nucleosomes and is associated with decreased primary graft dysfunction. J Heart Lung Transplant. 2023 Oct;42(10):1358-1362. doi: 10.1016/j.healun.2023.06.011. Epub 2023 Jun 20. PMID 37348689
Lindstedt S, Silverborn M, Lannemyr L, Pierre L, Larsson H, Grins E, Hyllen S, Dellgren G, Magnusson J. Design and Rationale of Cytokine Filtration in Lung Transplantation (GLUSorb): Protocol for a Multicenter Clinical Randomized Controlled Trial. JMIR Res Protoc. 2023 Dec 13;12:e52553. doi: 10.2196/52553. PMID 37855706

Identifiers

NCT: NCT05526950 · GLUSorb

Primary sources (government registries)

ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗