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

NCT05526950 | Recruiting DMC

• 1 other identifier: GLUSorb
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Transplant Failure; Lung Transplant; Complications

Outcome Measures

Primary Outcomes (4)

• 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.

  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

  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

  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

  72 hours after lung transplantation

Secondary Outcomes (14)

• 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 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 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 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

Other Outcomes (2)

• Safety endpoints

  First 72 hours after transplantation

• Exploratory endpoints

  First 4 years

Study Arms (2)

Treated

ACTIVE COMPARATOR

Treatment using the medical "cytokine adsorption" device in conjunction with lung transplantation

Device: Device: CytoSorb

Non-treated

NO INTERVENTION

No additional treatment in conjunction with lung transplantation

Interventions

Device: CytoSorb DEVICE

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

Treated

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligibility to undergo double lung transplantation at either trial site

You may not qualify if:

• 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

Sponsors & Collaborators

• Lund University Hospital: lead

Study Sites (1)

Sandra Lindstedt

Lund, Skåne County, 224 60, Sweden

RECRUITING

Related Publications (5)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 DERIVED

Study Officials

• Sandra Lindstedt, MD, PhD

  Skånes universitetssjukhus Lund

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sandra Lindstedt, MD,PhD

CONTACT

+46737220580; sandra.lindstedt_ingemansson@med.lu.se

Jesper Magnusson, MD, PhD

CONTACT

jesper.magnusson@vgregion.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: August 31, 2022
• First Posted: September 2, 2022
• Study Start: September 7, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029
• Last Updated: September 18, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)