Clinical trial NCT05242289: Cytokine Adsorption in Lung Transplantation
Official title: Cytokine Adsorption in Lung Transplantation: a Randomized Controlled Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lung Transplant Failure
Lung Transplant; Complications
Lead sponsor: Lund University Hospital
Sponsor class: OTHER
First posted: 2022-02-16
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The model consists of a randomized controlled pilot 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 (2). 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 pilot 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 pilot 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:

* Double lung transplantation
* Single organ failure

Exclusion Criteria:

* Re-transplantation
* Drug abuse
* Kidney failure
* Liver failure
* Diabetes mellitus

Primary outcomes:
measure: Oxygenation at 24 hours
timeFrame: 24 hours after lung transplantation
measure: Oxygenation at 48 hours
timeFrame: 48 hours after lung transplantation
measure: Oxygenation at 72 hours
timeFrame: 72 hours after lung transplantation
Secondary outcomes:
measure: Diffusion capacity of the lungs (DLCO)
timeFrame: 3 months after transplantation
measure: Primary Graft dysfunction after 24 hours
timeFrame: 24 hours after lung transplantation
measure: Primary Graft dysfunction after 48 hours
timeFrame: 48 hours after lungtransplantation
measure: Primary Graft dysfunction after 72 hours
timeFrame: 72 hours after lungtransplantation
measure: Urinary output as a measure of kidney function
timeFrame: First 3 months
measure: Creatinine levels and clearance as a measure of kidney function
timeFrame: First 3 months
measure: Urea levels as a measure of kidney function
timeFrame: First 3 months
measure: Rates of dialysis as a measure of kidney function
timeFrame: First 3 months
measure: Volume blood loss
timeFrame: First 24 hours
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Skåne University Hospital
state: Skåne Län
Study officials:
affiliation: Skånes universitetssjukhus Lund
name: Sandra Lindstedt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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: Ghaidan H, Fakhro M, Lindstedt S. Impact of allograft ischemic time on long-term survival in lung transplantation: a Swedish monocentric study. Scand Cardiovasc J. 2020 Oct;54(5):322-329. doi: 10.1080/14017431.2020.1781240. Epub 2020 Jun 23.
citation: Fakhro M, Ingemansson R, Skog I, Algotsson L, Hansson L, Koul B, Gustafsson R, Wierup P, Lindstedt S. 25-year follow-up after lung transplantation at Lund University Hospital in Sweden: superior results obtained for patients with cystic fibrosis. Interact Cardiovasc Thorac Surg. 2016 Jul;23(1):65-73. doi: 10.1093/icvts/ivw078. Epub 2016 Apr 6.