Cytokine Adsorption in Lung Transplantation

Cytokine Adsorption in Lung Transplantation: a Randomized Controlled Pilot Study

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.

Study Overview

• Status: Completed
• Conditions: Lung Transplant Failure; Lung Transplant; Complications
• Intervention / Treatment: Device: CytoSorb

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Skåne Län
    • Lund, Skåne Län, Sweden, 224 60
      • Skane University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Double lung transplantation
• Single organ failure

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treated; Treatment using the medical "cytokine adsorption" device in conjunction with lung transplantation	Device: CytoSorb; Medical device used hemoperfusion and cytokine adsorption in conjunction with lung transplantation.
No Intervention: Non-treated; No additional treatment in conjunction with lung transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygenation at 24 hours	Oxygenation expressed as the PaO2/FiO2 ratio at 24 hours	24 hours after lung transplantation
Oxygenation at 48 hours	Oxygenation expressed as the PaO2/FiO2 ratio at 48 hours	48 hours after lung transplantation
Oxygenation at 72 hours	Oxygenation expressed as the PaO2/FiO2 ratio at 72 hours	72 hours after lung transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Urea levels as a measure of kidney function	Urea levels will also be measured to assess kidney function.	First 3 months
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Lund University Hospital
• Investigators: Principal Investigator: Sandra Lindstedt, MD, PhD, Skånes Universitetssjukhus Lund

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• Pre print pre Clinical trail

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2022
• Primary Completion (Actual): August 30, 2023
• Study Completion (Actual): August 30, 2023

Study Registration Dates

• First Submitted: January 22, 2022
• First Submitted That Met QC Criteria: February 6, 2022
• First Posted (Actual): February 16, 2022

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 7, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: LUSorb

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No