Ex Vivo Normothermic Perfusion in Kidney Transplantation. (KidneyARK)

Multicenter, Prospective and Open-label Clinical Trial to Evaluate the Viability, Performance and Safety of ex Vivo Normothermic Perfusion in Kidney Transplantation From DCD and DBD Donors.

A multicenter, prospective and open-label clinical investigation to evaluate the viability, performance and safety of ex vivo normothermic perfusion in kidney transplantation from DCD and DBD donors.

Study Overview

• Status: Recruiting
• Conditions: Kidney Transplantation
• Intervention / Treatment: Device: Ex vivo normothermic perfusion; Device: Cold preservation

Detailed Description

The Ark Kidney is a medical device for ex vivo normothermic perfusion intended to create the conditions that allow kidneys to be resuscitated and / or preserved prior to transplantation. It consists of a permanent unit, which is retained after each perfusion, and a disposable circuit called the ARK Kidney Kidney Disposable Set (KDS), which must be replaced after perfusion to ensure sterile conditions.

It is a portable organ perfusion system designed to preserve a kidney by continuous perfusion of the donated organ with warm oxygenated perfusate supplemented with erythrocytes from the blood bank. The perfusion solution circulates continuously through the vascular network of the organ in a closed circuit. During perfusion, the system can monitor organ perfusion parameters, as well as the conditions of the perfusion solutions and the volume of urine generated during the perfusion.

The primary objective of the clinical study is to assess the viability, performance and safety of ex vivo normothermic perfusion with the Ark Kidney in kidney transplantation from DCD and DBD donors.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pedro Moreo Calvo, PhD; Phone Number: +34 876 013 826; Email: info@ebersmedical.com

Study Locations

• Spain
  • Zaragoza, Spain
    • Recruiting
    • Miguel Servet University Hospital
    • Contact: Pedro Moreo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients aged 18 years and older
2. Patients undergoing renal replacement therapy by means of dialysis and included in the waiting list for renal transplantation in their respective site.
3. Candidates to receive a first or second renal transplant from (i) a Maastricht type III (Maastricht classification) controlled DCD donor or (ii) a DBD donor aged 70 years or older.
4. Patients that have given informed consent in written form before their inclusion in the study. In case of compromised mental capacity, the approval and signature of a legal guardian will be required.
5. Patients compliant with the requirements of the study and without impediments to follow the instructions throughout the 1-year duration of the study.
6. Patients that meet the acceptance criteria for kidney transplant recipients established in the clinical site in agreement with usual clinical practice.

Exclusion Criteria:

1. Two or more previous kidney transplantations
2. Dual kidney transplantation or multivisceral transplantation (e.g. a pancreas-kidney transplantation)

3. Recipients of an organ with any of the following characteristics:

   1. Expected cold ischemia time before EVNP > 20 hours
   2. Organ from hepatitis B surface antigen-positive or hepatitis C viremic donor
   3. Organ with multiple arteries
4. Recipients with body mass index (BMI) > 40 kg/m2
5. Diagnosis of focal segmental glomerulosclerosis (FSGS) or membranoproliferative glomerulonephritis with high recurrence risk after transplantation in the eyes of the investigator.
6. Diagnosis of atypical hemolytic-uremic syndrome or thrombotic microangiopathy at the moment of inclusion
7. Diagnosis of antiphospholipid syndrome at the moment of inclusion
8. Panel-reactive antibodies (PRA) score > 50%
9. Known allergies to any of the components of the perfusate
10. Preexisting vascular disease that represents an extraordinary technical difficulty for the transplantation in the opinion of the investigator
11. Presence of clinically relevant donor-specific anti-HLA antibodies
12. ABO incompatibility
13. History of alcohol or drug abuse in the last two years
14. Use of normothermic regional perfusion during the organ harvesting process
15. Participation of the patient in another study or clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Ex vivo normothermic perfusion (EVNP) of the graft with the Ark Kidney System	Device: Ex vivo normothermic perfusion; Ex vivo normothermic perfusion (EVNP) of the renal graft with the Ark Kidney System; Other Names: EVNP
Active Comparator: Historical control group; Nonrandomized historical control group formed by patients transplanted without ex vivo normothermic perfusion (EVNP) in the period Sept 2015-Sept 2020, selected by retrospective matching.	Device: Cold preservation; Static cold storage (SCS) or hypothermic machine perfusion (HMP) of the renal graft; Other Names: SCS/HMP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of EVNP in kidney transplantation from DCD and DBD donors as evaluated by assessment of adverse events	The rate of adverse events will be compared in intervention arm and control arm	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient survival	Patient survival	1 year
Delayed graft function (DGF)	Delayed graft function (DGF), defined as the need for dialysis during the first week after transplantation	1 week
Duration (in days) of delayed graft function (DGF)	Duration (in days) of delayed graft function (DGF)	1 month
Proportion of patients with functional delayed graft function (fDGF)	Proportion of patients with functional delayed graft function (fDGF), defined as the failure of serum creatinine to decrease by at least 10% daily on 3 consecutive days during the first week post-transplant, without need for dialysis in that time.	1 week
Primary non-function (PNF)	Primary non-function (PNF)	1 week
Graft renal function (1 day)	Graft renal function, measured by the levels of serum creatinine and eGFR (CKD-EPI) at day 1 post-transplant in recipients who have not gone through dialysis after transplantation.	1 day
Graft renal function (3 days)	Graft renal function, measured by the levels of serum creatinine and eGFR (CKD-EPI) at day 3 post-transplant in recipients who have not gone through dialysis after transplantation.	3 days
Graft renal function (5 days)	Graft renal function, measured by the levels of serum creatinine and eGFR (CKD-EPI) at day 5 post-transplant in recipients who have not gone through dialysis in the previous three days.	5 days
Graft renal function (7 days)	Graft renal function, measured by the levels of serum creatinine and eGFR (CKD-EPI) at day 7 post-transplant in recipients who have not gone through dialysis in the previous three days.	7 days
Graft renal function (30 days)	Graft renal function, measured by the levels of serum creatinine and eGFR (CKD-EPI) at day 30 post-transplant in recipients who have not gone through dialysis in the previous three days.	30 days
Graft renal function (90 days)	Graft renal function, measured by the levels of serum creatinine and eGFR (CKD-EPI) at day 90 post-transplant in recipients who have not gone through dialysis in the previous three days.	90 days
Graft survival	Graft survival	1 year
Performance of EVNP in kidney transplantation from DCD and DBD donors as evaluated by the fraction of non-implanted organs because of the preservation method	The fraction of non-implanted organs will be compared in intervention arm and control arm	1 day
Viability of EVNP in kidney transplantation from DCD and DBD donors as evaluated by the ratio of planned vs. perfused organs	Viability of EVNP will be determined by the ratio of planned vs. perfused organs	1 day

Collaborators and Investigators

• Sponsor: Ebers Medical Technology, S.L.
• Investigators: Principal Investigator: Alex Gutierrez-Dalmau, MD, Miguel Servet University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 2, 2021
• First Submitted That Met QC Criteria: December 15, 2021
• First Posted (Actual): January 4, 2022

Study Record Updates

• Last Update Posted (Estimated): November 12, 2024
• Last Update Submitted That Met QC Criteria: November 8, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Transplantation; Kidney; Delayed Graft Function; DCD; DBD; EBERS; EVNP; Ex vivo normothermic perfusion
• Other Study ID Numbers: KidneyARK

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