Clinical trial NCT05526950: Cytokine Filtration in Lung Transplantation: A Swedish National Study (GLUSorb)
Official title: Cytokine Filtration in Lung Transplantation - a Randomised, Controlled, Multicentre Clinical Trial (GLUSorb)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Lung Transplant Failure
Lung Transplant; Complications
Lead sponsor: Lund University Hospital
Sponsor class: OTHER
First posted: 2022-09-02
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The model consists of a randomized controlled in human patients using a "cytokine adsorption" device.

Lung transplant recipients are randomized to either the treatment group which undergoes cytokine adsorption using the medical device compared to the control group which has not received the cytokine adsorber.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

• Eligibility to undergo double lung transplantation at either trial site

Exclusion Criteria:

1. Age \<18 years
2. Previous organ transplantation
3. Presence of any conditions at the time of surgery that require immunosuppressive therapy. Immunosuppressive therapy is defined as:

   1. Cyclosporine, Tacrolimus, Everolimus, or Sirolimus, minimum 1 month of treatment prior to transplantation and active treatment at the time of transplantation.
   2. Any form of antibody-based treatment that is known for having an immunomodulatory effect taken up to 1 week before transplantation.
4. Non-consent

Primary outcomes:
measure: To determine whether cytokine reduction by cytokine filtration leads to improved oxygenation in patients undergoing lung transplantation.
timeFrame: First 72 hours after lung transplantation
measure: To determine whether cytokine reduction by cytokine filtration leads to improved oxygenation in patients undergoing lung transplantation. Oxygenation at 24 hours
timeFrame: 24 hours after lung transplantation
measure: To determine whether cytokine reduction by cytokine filtration leads to improved oxygenation in patients undergoing lung transplantation. Oxygenation at 48 hours
timeFrame: 48 hours after lung transplantation
measure: To determine whether cytokine reduction by cytokine filtration leads to improved oxygenation in patients undergoing lung transplantation. Oxygenation at 72 hours
timeFrame: 72 hours after lung transplantation
Secondary outcomes:
measure: To determine whether cytokine reduction by cytokine filtration improves levels of plasma inflammatory markers (including cytokines) in patients undergoing lung transplantation.
timeFrame: 0-72 hours (0-3 days) after lung transplantation
measure: To determine whether cytokine reduction by cytokine filtration decreases lung infiltrates and oedema in patients undergoing lung transplantation
timeFrame: 0-72 hours (0-3 days) after lung transplantation
measure: To determine whether cytokine reduction by cytokine filtration improves arterial blood gas measures in patients undergoing lung transplantation
timeFrame: 0-72 hours (0-3 days) after lung transplantation
measure: To determine whether cytokine reduction by cytokine filtration decreases severity of primary graft dysfunction (PGD) in patients undergoing lung transplantation
timeFrame: 0-72 hours (0-3 days) after lung transplantation
measure: To determine whether cytokine reduction by cytokine filtration decreases incidence of primary graft dysfunction (PGD) in patients undergoing lung transplantation
timeFrame: 0-72 hours (0-3 days) after lung transplantation
measure: To determine whether cytokine reduction by cytokine filtration decreases need for norepinephrine in patients undergoing lung transplantation
timeFrame: 0-72 hours (0-3 days) after lung transplantation
measure: To determine whether cytokine reduction by cytokine filtration decreases mortality in patients undergoing lung transplantation
timeFrame: First 4 years
measure: To determine whether cytokine reduction by cytokine filtration improves diffusion capacity of the lungs (DLCO) in patients undergoing lung transplantation
timeFrame: First 4 years
measure: 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
timeFrame: First 4 years
measure: To determine whether cytokine reduction by cytokine filtration improves occurrence of any acute rejection episodes in patients undergoing lung transplantation
timeFrame: First 4 years
measure: To determine whether cytokine reduction by cytokine filtration improves Chest CT in patients undergoing lung transplantation
timeFrame: First 4 years
measure: To determine whether cytokine reduction by cytokine filtration improves presence of any CLAD in patients undergoing lung transplantation
timeFrame: First 4 years
measure: To determine whether cytokine reduction by cytokine filtration improves kidney function in patients undergoing lung transplantation
timeFrame: First 4 years
measure: To determine whether cytokine reduction by cytokine filtration improves quality of life (QOL) in patients undergoing lung transplantation
timeFrame: First 4 years
Other outcomes:
measure: Safety endpoints
timeFrame: First 72 hours after transplantation
measure: Exploratory endpoints
timeFrame: First 4 years
Locations:
city: Lund
country: Sweden
facility: Sandra Lindstedt
state: Skåne Län
Study officials:
affiliation: Skånes universitetssjukhus Lund
name: Sandra Lindstedt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.