- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03136848
The Feasibility and Safety of Normothermic ex Vivo Kidney Perfusion (NEVKP)
A Single Centre Study of the Feasibility and Safety of Using Normothermic ex Vivo Machine Perfusion to Store Human Kidneys for Transplantation.
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Ontario
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Toronto, Ontario, Canada, M5G 2C4
- University Health Network
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
How is the study designed?
Design Details
- Primary Purpose: OTHER
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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
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The perfusion "device" will circulate warmed, oxygenated blood-based perfusate ("Normothermic ex-vivo kidney perfusion solution-Toronto") through the kidney.
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What is the study measuring?
Primary Outcome Measures
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
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planned versus actual kidney perfusions to assess study feasibility
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assessed 3 months after enrollment of final participant, or up to 48 months, whichever is earlier
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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
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organ discard or graft failure directly attributable to the use of normothermic perfusion
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from date of first actual intervention to date last participant completes the study followup period of 3 months post-intervention
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
duration of post-transplant dialysis
Time Frame: 3 months post-kidney transplantation
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3 months post-kidney transplantation
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rate of primary graft non-function compared to historical, case-matched controls
Time Frame: 3 months post-kidney transplantation
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3 months post-kidney transplantation
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Degree of Ischemia-reperfusion injury as assessed by post-reperfusion kidney biopsies
Time Frame: assessed 3 months after enrollment of final participant
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Pre--implantation kidney biopsies will be graded according to standard histological criteria and assess for degree of ischemia-reperfusion injury
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assessed 3 months after enrollment of final participant
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Rate of delayed graft function
Time Frame: 3 months post-kidney transplantation
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3 months post-kidney transplantation
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Collaborators and Investigators
Investigators
- Principal Investigator: Markus Selzner, MD, Surgeon, MOT, UHN
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- 15-9907-A
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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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