PROlonged Ex-vivo Normothermic Machine PERfusion for Kidney Regeneration (PROPER)

The investigators would like to introduce and clinically evaluate prolonged normothermic machine perfusion (PNMP) to preserve and assess high-risk donor kidneys prior to transplantation.

Study Overview

• Status: Recruiting
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Procedure: Prolonged normothermic machine perfusion

Detailed Description

Currently kidney transplantation is the only viable option for patients with kidney failure to regain quality of life and health. The number of organs available for transplantation is insufficient with a widening gap between supply and demand. Nowadays, centers accept older and higher risk donor organs with co-morbidity, often leading to non-function, complications and with half of the patients back on dialysis within 15 years. Furthermore, many donor kidneys have to be discarded as too damaged and beyond repair. Increasing the quality and therefore transplantability of these high-risk donor organs could significantly increase the donor kidney pool.

Using prolonged normothermic perfusion of marginal donor organs, the investigators aim to kick start regeneration in the kidney before transplantation, improving function and survival long-term. Furthermore, the choice to accept or decline a donor kidney organ is currently based on subjective criteria and causes great uncertainty amongst clinicians. There is a dire need for tools to aid in decision making and reduce this uncertainty. Biomarkers predictive of graft regeneration are lacking. Samples from perfused kidneys and donor recipients will be collected and analysed to allow the formulation of a kidney fitness index.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Asel Arykbaeva; Phone Number: +31657216416; Email: a.s.arykbaeva@lumc.nl
• Study Contact Backup: Name: Dorottya K De Vries, MD PhD; Email: d.k.de_vries@lumc.nl

Study Locations

• Netherlands
  • Groningen, Netherlands
    • Recruiting
    • University Medical Center Groningen
    • Contact: Robert A Pol, MD PhD; Email: r.pol@umcg.nl
    • Principal Investigator: Robert A Pol, MD PhD
  • Leiden, Netherlands
    • Recruiting
    • Leiden University Medical Center
    • Contact: Asel Arykbaeva; Email: a.s.arykbaeva@lumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients undergoing 1st or 2nd kidney transplant
• Patients undergoing a kidney transplantation from DCD Maastricht III & V
• Transplant recipients aged ≥ 18 years
• Written informed consent

Exclusion Criteria:

• Patients undergoing 3rd or subsequent kidney transplant
• Patients undergoing a kidney transplantation from DCD Maastricht I, II & IV
• Transplant recipients aged < 18 years
• Patients receiving multi-organ transplants
• ABO/HLA incompatible transplants
• Highly sensitized patients with a panel-reactive antibody (PRA) ≥85%
• Kidneys with CIT > 12 hrs at the point of arrival at transplant centre
• Kidneys with complex vascular anatomy (≥3 arteries, artery which cannot be can-nulated or attached to the patch holder)
• Kidneys explanted from a donor on normothermic regional perfusion

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Prolonged normothermic machina perfusion; Eligible and consenting patients who will receive a donor kidney will be included for participation in this study. Current practice is to preserve donor kidneys on hypothermic machine perfusion (HMP). In this study, donor kidneys (n=18) will be taken off the HMP after arrival in the transplant center. These will then be perfused with oxygenated perfusate using the NMP device following an optimised NMP protocol.

Procedure: Prolonged normothermic machine perfusion; First, a cohort of DCD kidneys (n=6) will be subjected to 1 hour of NMP and subsequently transplanted [NMP1]. Before extending the duration, secondary endpoints will be evaluated. Thereafter, the duration of NMP will be prolonged to 3 hours (n=6) [PNMP3] and consequently 6 hours (n=6) [PNMP6].

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
glomerular filtration rate (GFR)	renal function defined by the estimated glomerular filtration rate (eGFR) calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation	6 months post transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
glomerular filtration rate (GFR)	renal function defined by the estimated glomerular filtration rate (eGFR) calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation	1 month post transplantation
glomerular filtration rate (GFR)	renal function defined by the estimated glomerular filtration rate (eGFR) calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation	3 months post transplantation
primary non-function	defined as permanent lack of graft function from the time of transplantation, was diagnosed when a kidney graft was well perfused (confirmed by ultrasound examination) but never functioned, necessitating dialysis after kidney transplantation	6 months post transplantation
delayed graft function (DGF)	defined as the need for postoperative dialysis during the first 7 days after transplantation	6 months post transplantation
patient and graft survival	time from transplant to patient death, and graft failure	6 months post transplantation
adverse events	defined as any undesirable experience occurring to a subject during the study, whether or not considered related to the normothermic machine perfusion of the donor kidney prior to transplantation	6 months post transplantation
postoperative complications	graded according to the comprehensive complication index	6 months post transplantation

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Investigators: Principal Investigator: Ian PJ Alwayn, MD PhD, Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2021
• Primary Completion (ANTICIPATED): July 1, 2022
• Study Completion (ANTICIPATED): January 1, 2023

Study Registration Dates

• First Submitted: June 24, 2020
• First Submitted That Met QC Criteria: December 30, 2020
• First Posted (ACTUAL): January 5, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 3, 2022
• Last Update Submitted That Met QC Criteria: December 13, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: kidney transplantation; renal transplantation; normothermic machine perfusion
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: NL76344

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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