The Feasibility and Safety of Normothermic ex Vivo Kidney Perfusion

NCT03136848 | Completed

• 1 other identifier: 15-9907-A
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Kidney transplantation is the treatment of choice for end-stage kidney failure, but access to transplantation is limited by a severe shortage of donor organs. Although the use of kidneys from higher risk deceased donors has increased the availability of organs, these grafts are associated with a greater risk of delayed function, inferior performance, and shorter survival than standard criteria donor kidneys. The current standard of care for kidney graft preservation prior to transplantation is static cold storage. Preliminary results from large animal kidney transplantation studies and a human clinical trial suggest that normothermic machine perfusion of kidneys prior to transplantation may ameliorate the injury sustained by kidney grafts during cold static preservation, allow assessment of organ viability prior to transplantation, and reduce the risk of delayed graft function or non-function. Such a strategy may not only improve the performance of kidneys that are currently considered acceptable for transplantation, but may also facilitate the assessment and utilization of kidneys that are currently not considered for transplantation. This study will examine the feasibility and safety of normothermic ex vivo perfusion of human kidneys prior to transplantation. The study will evaluate kidney function after transplantation using standard clinical parameters. Study participants will be followed for 3 months following transplantation and their outcomes recorded. Feasibility will be measured using the ratio of actual:eligible kidney grafts preserved by normothermic ex vivo perfusion and will also take into account logistical issues with respect to implementation and ease of use of the ex vivo perfusion device. Safety will be assessed by rates of device failure resulting in organ discard, primary graft non-function, delayed graft function, graft failure, and recipient mortality.

Conditions

Kidney Transplantation

Keywords

perfusion

Outcome Measures

Primary Outcomes (2)

• the ratio of actual / eligible kidney grafts subjected to study intervention.

  planned versus actual kidney perfusions to assess study feasibility

  assessed 3 months after enrollment of final participant, or up to 48 months, whichever is earlier

• The rate of kidney discard or graft failure attributable to the study intervention

  organ discard or graft failure directly attributable to the use of normothermic perfusion

  from date of first actual intervention to date last participant completes the study followup period of 3 months post-intervention

Secondary Outcomes (4)

• duration of post-transplant dialysis

  3 months post-kidney transplantation

• rate of primary graft non-function compared to historical, case-matched controls

  3 months post-kidney transplantation

• Degree of Ischemia-reperfusion injury as assessed by post-reperfusion kidney biopsies

  assessed 3 months after enrollment of final participant

• Rate of delayed graft function

  3 months post-kidney transplantation

Study Arms (1)

Normothermic perfusion

EXPERIMENTAL

Kidneys retrieved from deceased donors will undergo the study intervention consisting of 4-10 hours of Normothermic ex-vivo perfusion using a blood-based solution, prior to implantation in the transplant recipient

Drug: Normothermic ex-vivo kidney perfusion Solution -Toronto

Interventions

Normothermic ex-vivo kidney perfusion Solution -Toronto DRUG

The perfusion "device" will circulate warmed, oxygenated blood-based perfusate ("Normothermic ex-vivo kidney perfusion solution-Toronto") through the kidney.

Normothermic perfusion

Eligibility Criteria

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

You may qualify if:

• Single kidneys from DBD (donation after brain death) and DCD (donation after cardiac death) donors
• Kidney is subjected to a maximum of 12 hours of cold storage prior to beginning of NEVKP (normothermic ex vivo kidney perfusion)
• Kidney meets parameters that are acceptable for transplantation according to the study transplant centre's current clinical practices.

You may not qualify if:

• Kidneys from living donors
• Kidneys that would be declined for transplantation under the study centre's current clinical practice
• Kidneys with multiple arteries.
• Kidney grafts from donors positive for Hepatitis B surface antigen or Hepatitis C viremia.
• Adult male and female patients (18 years or more), active on the waiting list for kidney transplantation; able to give informed consent.
• Patients with focal segmental glomerulosclerosis (FSGS)
• Patients with a diagnosis of atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis, or thrombotic microangiopathy Patients with a calculated Panel Reactive Antibody (cPRA) greater than 95%
• Patients with known allergies to any of the perfusion solution components
• Patients undergoing retransplantation
• Recipients with pre-existing vascular disease posing technical challenges for transplantation
• Recipients with any clinically-relevant positive DSA (donor-specific antibody) identified
• Transplantation of more than one organ (e.g. liver/pancreas and kidney)
• Refusal of informed consent
• Recipients receiving double kidney grafts (i.e. both kidneys from one donor being transplanted into a single recipient)

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (1)

• Mazilescu LI, Urbanellis P, Kim SJ, Goto T, Noguchi Y, Konvalinka A, Reichman TW, Sayed BA, Mucsi I, Lee JY, Robinson LA, Ghanekar A, Selzner M. Normothermic Ex Vivo Kidney Perfusion for Human Kidney Transplantation: First North American Results. Transplantation. 2022 Sep 1;106(9):1852-1859. doi: 10.1097/TP.0000000000004098. Epub 2022 Mar 1.

  PMID: 35238854 DERIVED

Study Officials

• Markus Selzner, MD

  Surgeon, MOT, UHN

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A pilot study of procedural feasibility involving both device and drug (organ perfusate solution).

Study Record Dates

• First Submitted: March 8, 2017
• First Posted: May 2, 2017
• Study Start: December 19, 2016
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: February 14, 2023

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)