Cytokine Adsorption in Lung Transplantation

Lung Transplant; Complications Clinical Trial

Official title:

Cytokine Adsorption in Lung Transplantation: a Randomized Controlled Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05242289
• Other study ID #: LUSorb
• Status: Completed
• Phase: N/A
• Start date: March 2, 2022
• Est. completion date: August 30, 2023

Study information

• Verified date: September 2023
• Source: Lund University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 30, 2023
• Est. primary completion date: August 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Double lung transplantation

• Single organ failure

Exclusion Criteria:

• Re-transplantation

• Drug abuse

• Kidney failure

• Liver failure

• Diabetes mellitus

Related Conditions & MeSH terms

• Lung Transplant Failure
• Lung Transplant; Complications

Intervention

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

Locations

Country	Name	City	State
Sweden	Skåne University Hospital	Lund	Skåne Län

Sponsors (1)

Lead Sponsor	Collaborator
Lund University Hospital

Country where clinical trial is conducted

Sweden, 

References & Publications (3)

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 — View 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. — View 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/cel — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Oxygenation at 24 hours	Oxygenation expressed as the PaO2/FiO2 ratio at 24 hours	24 hours after lung transplantation
Primary	Oxygenation at 48 hours	Oxygenation expressed as the PaO2/FiO2 ratio at 48 hours	48 hours after lung transplantation
Primary	Oxygenation at 72 hours	Oxygenation expressed as the PaO2/FiO2 ratio at 72 hours	72 hours after lung transplantation
Secondary	Diffusion capacity of the lungs (DLCO)	The primary function of the lungs is oxygenation of the blood and exhalation of carbon dioxide (CO2) from the blood. The ability of the lungs to perform this depends on a good alveolar ventilation, an even relationship between perfusion and ventilation, and good diffusion potential for oxygen (O2) and CO2 between alveolar, capillary and hemoglobin. This outcome will be measured through the diffusing capacity for carbon monoxide (DLCO)	3 months after transplantation
Secondary	Primary Graft dysfunction after 24 hours	Primary graft dysfunction (PGD) 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 over the first 72 hours after transplantation and is defined by evaluation of both the PaO2/FiO2 ratio and presence of lung edema on chest x-ray.	24 hours after lung transplantation
Secondary	Primary Graft dysfunction after 48 hours	PGD must also be assessed throughout the 72 hour period following completion of the transplantation and as such, this outcome will consist of the evaluation for PGD in the recipient 48 hours post-transplantation.	48 hours after lungtransplantation
Secondary	Primary Graft dysfunction after 72 hours	PGD must also be assessed throughout the 72 hour period following completion of the transplantation and as such, this outcome will consist of the evaluation for PGD in the recipient 72 hours post-transplantation.	72 hours after lungtransplantation
Secondary	Urinary output as a measure of kidney function	Kidney function is often impaired in transplant subjects due to the surgery itself but also secondary to drugs. The degree of acute kidney injury (AKI) can be assessed in part through measure of the urinary output.	First 3 months
Secondary	Creatinine levels and clearance as a measure of kidney function	To further assess the incidence of AKI, creatinine levels and its clearance will be measured.	First 3 months
Secondary	Urea levels as a measure of kidney function	Urea levels will also be measured to assess kidney function.	First 3 months
Secondary	Rates of dialysis as a measure of kidney function	The incidence of patients requiring dialysis will be also used to assess the frequency of AKI in the study population.	First 3 months
Secondary	Volume blood loss	Given the nature of the transplantation itself as a major surgery, blood loss is expected after surgery and the volume of blood loss (mL) after surgery will be measured as a surgical outcome.	First 24 hours

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