Intermittent Versus Continuous Surface O2 During HMP of DCD Kidneys (HMPO2)

A Prospective Feasibility Trail to Compare the Efficacy of Intermittent Surface Oxygenation With Continuous Surface Oxygenation During Hypothermic Machine Perfusion of Kidneys Donated After Circulatory Death

The aim of the study is to evaluate the feasibility of this bubble and surface oxygenation and to determine the optimal timing of surface oxygenation (continuous versus intermittent) as alternative for membrane-oxygenated kidneys, originating from DCD donors, during HMP on early graft function in clinical practice.

Study Overview

• Status: Recruiting
• Conditions: Ischemia Reperfusion Injury; Kidney Transplant; Complications; Delayed Graft Function; Mitochondrial
• Intervention / Treatment: Drug: Oxygen

Detailed Description

Kidneys originating from deceased donors after circulatory death (DCD), category 3 and 5 (controlled) will be preserved from procurement until transplantation on hypothermic machine perfusion conditions and prospectively randomized into 2 study groups: 1) intermittent surface oxygenation during HMP (surface oxygenation interrupted during organ transport (2-4h)(I-HMPO2 group), and 2) continuous surface oxygenation during HMP (surface oxygenation during the whole machine preservation period included organ transport)(C-HMPO2 group).

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Tom Darius, Phd; Phone Number: 003227642218; Email: tom.darius@saintluc.uclouvain.be
• Study Contact Backup: Name: Nathalie Staumont; Phone Number: 003227642218; Email: nathalie.Staumont@saintluc.uclouvain.be

Study Locations

• Belgium
  • Woluwé-Saint-Lambert
    • Brussel, Woluwé-Saint-Lambert, Belgium, 1200
      • Recruiting
      • Cliniques Universitaires Saint-Luc
      • Contact: Tom Darius, MD, PhD; Phone Number: +3227646065; Email: tom.darius@saintluc.uclouvain.be
      • Contact: Nathalie Staumont; Phone Number: +3227642218; Email: nathalie.staumont@saintluc.uclouvain.be

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Listed for a renal transplantation due to end stage renal disease
• Willingness to comply with the protocol procedures for the duration of the study included scheduled follow-up visits and examinations.

Exclusion Criteria:

• Multi-organ recipients
• Dual kidney transplantation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: I-HMPO2; intermittent surface oxygenation during hypothermic machine perfusion (surface oxygenation interrupted during organ transport)	Drug: Oxygen; Active oxygenation during hypothermic machine perfusion by bubble and surface oxygenation. Intermittent surface oxygenation is compared with continuous surface oxygenation during hypothermic machine perfusion; Other Names: feasibility of bubble and surface oxygenation applied to the LifePort Kidney Transporter (Organ Recovery Systems, Diegem, Belgium)
Active Comparator: C-HMPO2; continuous surface oxygenation during HMP (surface oxygenation during the whole machine preservation period included organ transport)	Drug: Oxygen; Active oxygenation during hypothermic machine perfusion by bubble and surface oxygenation. Intermittent surface oxygenation is compared with continuous surface oxygenation during hypothermic machine perfusion; Other Names: feasibility of bubble and surface oxygenation applied to the LifePort Kidney Transporter (Organ Recovery Systems, Diegem, Belgium)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional delayed graft function	defined as the absence of a decrease in the serum creatinine level of at least 10% per day for at least 3 consecutive days in the first 7 days after transplantation (not including patients in whom acute rejection of calcineurin inhibitor toxicity is proven on biopsy)	first 7 days after transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for dialysis after transplantation	Number of dialysis sessions after transplantation	0-30 days after transplantation
Delayed graft function	defined as the need for dialysis in the first 7 days after transplantation and preceding the return of kidney function	first 7 days after transplantation
Serum creatinine reduction ratio	alternative definition of DGF= CRR2 < or = 30%	Day 1-2 after transplantation
Graft survival	Functional kidney graft at 7 days, 3, 6, and 12 months	From 1-365 days after transplantation
Patient survival (censored and uncensored for death)	Patient survival at 7 days, 3, 6, and 12 months	From 1-365 days after transplantation
Glomerular filtration rate at 1 year after transplantation	24-hour creatinine clearance	At 1 year after transplantation (window 30 days)
Estimated glomerular filtration rate	eGFR defined by the CKD-EPI equation (Chronic Kidney Disease Epidemiology Collaboration) at 3, 6 and 12 months after transplantation	At 3, 6, and 12 months after transplantation with window of 10 days
Primary non-function	defined as the continued need for dialysis at 3 months after transplantation	Until 3 months after transplantation
Biopsy-proven acute rejection	Biopsy-proven acute rejection during the 1 year after transplantation	Until 1 year after transplantation with window of 10 days
Metabolic analysis on kidney preservation tissue	Metabolic analysis by 1D proton NMR (e.g., succinate, lactate, acetate, formate, hypoxanthine) on a tissue sample taken before (= baseline) and at the end of the preservation period before transplantation of the kidney	Baseline and pre-surgery
Metabolic analysis on kidney preservation tissue	Metabolic analysis by liquid chromatography coupled to electrospray ionization mass spectrometry (LC-ESI-MS) (succinate, glutamate, lactate, ATP, ADP, AMP, NADH, NAD+) on a tissue sample taken before (= baseline) and at the end of the preservation period before transplantation of the kidney	Baseline and pre-surgery
Metabolic analysis on preservation fluid	Metabolic analysis by 1D proton NMR and fluorescence on a perfusion fluid sample taken before (= baseline) and at the end of the preservation period before transplantation of the kidney	Baseline and pre-surgery

Collaborators and Investigators

• Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Investigators: Principal Investigator: Tom Darius, MD, PhD, Cliniques Universitaires Saint-Luc

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2022
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: June 17, 2022
• First Submitted That Met QC Criteria: June 23, 2022
• First Posted (Actual): June 24, 2022

Study Record Updates

• Last Update Posted (Actual): May 23, 2024
• Last Update Submitted That Met QC Criteria: May 22, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Hypothermic oxygenated machine perfusion; Kidney preservation; bubble and surface oxygenation
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Reperfusion Injury; Delayed Graft Function
• Other Study ID Numbers: 2021/21MAI/239

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
• product manufactured in and exported from the U.S.: No