Confirming Permanent Lack of Blood Flow to the Brain During A-NRP DCC Organ Transplant (CONCLUDE)

Confirming the Permanent Cessation of Intracranial Circulation During Abdominal Normothermic Regional Perfusion After the Determination of Death by Circulatory Criteria

This study aims to evaluate the surgical technique used in Abdominal Normothermic Regional Perfusion (A-NRP) in death determination by circulatory criteria (DCC) organ donors. The proposed study will demonstrate that there is no resumption of brain blood flow or activity during the A-NRP procedure. This will be assessed using multimodal neuromonitoring protocol that enables continuous focused monitoring of brain blood flow and activity during A-NRP. This will provide evidence that brain blood flow and activity does not resume during NRP and ensure donor safety in using this technique in standard of care practice.

Study Overview

• Status: Recruiting
• Conditions: Organ Transplant
• Intervention / Treatment: Other: Neuromonitoring

Detailed Description

This will be a multi-centre prospective observational cohort study that will enroll eligible DCC donors at participating donation hospitals. Participating programs will implement the A-NRP processes and organ recovery at the donation sites. Neurocritical care teams and donation physicians at the donation site and independent of transplant teams will implement neuromonitoring using the following modalities:

1. Transcranial colour-coded Doppler (TCCD) as a measure of brain blood flow,
2. Electroencephalography (EEG), as a measure of cortical brain electrophysiologic activity, and
3. Somatosensory evoked potentials (SSEP) or brainstem auditory evoked potentials (BAEP), as a measure of brainstem electrophysiologic activity.

The neuromonitoring team will interpret observed signals in real-time during the A-NRP process. This study will confirm whether current A-NRP surgical safeguards ensure maintenance of permanent cessation of brain blood flow and/or activity during A-NRP and will guide the adoption of A-NRP in Ontario.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Crystal Engelage, PhD; Phone Number: 37517 519-685-8500; Email: Crystal.Engelage@lhsc.on.ca
• Study Contact Backup: Name: Anton Skaro, MD PhD; Phone Number: 519-663-2904; Email: Anton.Skaro@lhsc.on.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Recruiting
      • London Health Sciences Centre
      • Contact: Crystal Engelage, PhD; Phone Number: 37517 519-685-8500; Email: Crystal.Engelage@lhsc.on.ca
    • Toronto, Ontario, Canada, M5T 2S8
      • Not yet recruiting
      • Toronto Western Hospital
      • Contact: Erin Winter, HBSc; Phone Number: 6093 416-340-4800; Email: Erin.Winter@uhn.ca
      • Principal Investigator: Markus Selzner, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients in critical care at participating study centers who qualify for DCC organ donation and whose families/surrogate decision makers have consented to DCC organ donation according to current criteria of the participating transplant programs.

Description

Inclusion Criteria:

• ≤ 18 years of age
• Potential DCC donors whose families/surrogate decision makers have consented to DCC organ donation according to current criteria of the participating transplant programs. These may include patients donating a liver, kidneys, pancreas, and/or lungs; please see Appendix A for organ specific donor inclusion criteria.

Exclusion Criteria:

• < 18 years of age
• DCC donors who proceed to donation following medical assistance in dying or those who are able to provide first-person consent at the time of donation
• Injuries that anatomically preclude the use of neurological monitoring

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

DCC Donors; Standard criteria DCC donors will be undergoing the A-NRP perfusion process to recondition organs prior to procurement. Multimodal neuromonitors will be placed on the donor prior to withdrawal of life support and readings will be recorded during the withdrawal process and for the duration of the A-NRP perfusion process. The neuromonitoring team will be looking for evidence of brain blood flow or activity.

Other: Neuromonitoring; Multimodal neuromonitoring will include: Transcranial colour-coded Doppler (TCCD), Electroencephalography (EEG), and Somatosensory evoked potentials (SSEP) or brainstem auditory evoked potentials (BAEP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Donor resumption of brain blood flow and/or activity	Proportion of enrolled patients who have resumption of brain blood flow and/or activity during A-NRP on any neuromonitor and that is confirmed by neurocritical care physician and that results in termination of A-NRP	Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Donor accrual rate	Number of eligible donors who are enrolled in the study and complete study procedures	Through study completion, an average of 1 year
Consent rate	Number of donors who consent to study procedures divided by the number of donors approached for study consent (target ≥ 80%)	Through study completion, an average of 1 year
Neuromonitoring modalities	Number of neuromonitoring modalities used per patient and reasons for excluding specific modalities	Through study completion, an average of 1 year
Duration and proportion of neuromonitoring signal	Duration of continuous neuromonitoring and proportion of total recording time with adequate signal per patient (velocity waveforms for TCCD, uv/mm for EEG, brainstem auditory evoked potentials (BAEP) signal, and somatosensory evoked potentials (SSEP) signal)	Through study completion, an average of 1 year
Neuromonitoring failure	Proportion of enrolled patients who had failure of neuromonitoring equipment during recording	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Western University, Canada
• Collaborators: University Health Network, Toronto
• Investigators: Principal Investigator: Anton Skaro, MD PhD, London Health Sciences Centre/Lawson Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 16, 2023
• First Submitted That Met QC Criteria: May 31, 2023
• First Posted (Actual): June 1, 2023

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: transplant; brain activity; neuromonitoring; A-NRP
• Other Study ID Numbers: 4436

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