The Feasibility and Safety of Normothermic ex Vivo Kidney Perfusion (NEVKP)

February 12, 2023 updated by: University Health Network, Toronto

A Single Centre Study of the Feasibility and Safety of Using Normothermic ex Vivo Machine Perfusion to Store Human Kidneys for Transplantation.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Kidney transplantation is the treatment of choice for suitable patients with end-stage renal disease as it results in lower morbidity and mortality rates when compared to dialysis. Unfortunately, the number of patients referred for transplantation has grown more quickly than the number of suitable grafts from deceased donors.

The use of higher risk organs has expanded the donor pool but at a great cost due to the higher probability that higher risk kidneys will never function (primary non-function, PNF), or will have delayed graft function (DGF). The current standard of care for kidney graft preservation prior to transplantation is static cold storage but higher-risk deceased donor kidneys are particularly vulnerable to the effects of 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. Kidneys will be retrieved in the standard fashion and stored cold during transit. Upon arrival at the study transplant centre, kidneys will begin perfusion with a normothermic near-physiologic, blood-based solution. Perfusion will last 1-10 hours.

The study will evaluate kidney function after transplantation using standard clinical parameters. Study participants (n=25) 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
13

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
        • University Health Network

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria (Organ):

  • 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.

Exclusion Criteria (Organ):

  • 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.

Inclusion Criteria (Participants):

• Adult male and female patients (18 years or more), active on the waiting list for kidney transplantation; able to give informed consent.

Exclusion Criteria (Participants):

  • 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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Normothermic perfusion
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
The perfusion "device" will circulate warmed, oxygenated blood-based perfusate ("Normothermic ex-vivo kidney perfusion solution-Toronto") through the kidney.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
the ratio of actual / eligible kidney grafts subjected to study intervention.
Time Frame: assessed 3 months after enrollment of final participant, or up to 48 months, whichever is earlier
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
Time Frame: from date of first actual intervention to date last participant completes the study followup period of 3 months post-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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
duration of post-transplant dialysis
Time Frame: 3 months post-kidney transplantation
3 months post-kidney transplantation
rate of primary graft non-function compared to historical, case-matched controls
Time Frame: 3 months post-kidney transplantation
3 months post-kidney transplantation
Degree of Ischemia-reperfusion injury as assessed by post-reperfusion kidney biopsies
Time Frame: assessed 3 months after enrollment of final participant
Pre--implantation kidney biopsies will be graded according to standard histological criteria and assess for degree of ischemia-reperfusion injury
assessed 3 months after enrollment of final participant
Rate of delayed graft function
Time Frame: 3 months post-kidney transplantation
3 months post-kidney transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Health Network, Toronto

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Markus Selzner, MD, Surgeon, MOT, UHN

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 19, 2016

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 8, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 26, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 2, 2017

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 14, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 12, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2022

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 15-9907-A

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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