PROlonged Ex-vivo Normothermic Machine PERfusion for Kidney Regeneration

End Stage Renal Disease Clinical Trial

— PROPER  

Official title:

PROlonged Ex-vivo Normothermic Machine PERfusion for Kidney Regeneration

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04693325
• Other study ID #: NL76344
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2021
• Est. completion date: January 2023

Study information

• Verified date: December 2021
• Source: Leiden University Medical Center
• Contact: Asel Arykbaeva
• Phone: +31657216416
• Email: a.s.arykbaeva[@]lumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: January 2023
• Est. primary completion date: July 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Failure, Chronic

Intervention

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].

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Center	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	delayed graft function (DGF)	defined as the need for postoperative dialysis during the first 7 days after transplantation	6 months post transplantation
Secondary	patient and graft survival	time from transplant to patient death, and graft failure	6 months post transplantation
Secondary	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
Secondary	postoperative complications	graded according to the comprehensive complication index	6 months post transplantation