CT-Perfusion for Neurological Diagnostic Evaluation (INDex-CTP)

April 22, 2024 updated by: Centre hospitalier de l'Université de Montréal (CHUM)

CT-Perfusion for Neurological Diagnostic Evaluation: a Prospective Canadian Multicenter Diagnostic Test Study

For the purpose of organ donation after neurological determination of death (NDD), death must be declared using a set of standardized clinical criteria. When a full clinical evaluation cannot be completed, additional neuroimaging ancillary testing is required. The ideal ancillary test for NDD would demonstrate no cerebral blood flow, be free of false-positive and false negative results, rapid, safe, readily available, non-invasive, and inexpensive. No current ancillary test for NDD meets these criteria. Computed tomography (CT) perfusion has the characteristics of an ideal test for NDD, but has not been evaluated for routine clinical use for NDD.

The overarching goal of this project is to improve the NDD process by establishing CT-perfusion as the ideal ancillary test. A large prospective Canadian multi-centre diagnostic cohort study will be conducted to validate CT-perfusion for the neurological determination of death.

Specific objectives are:

Primary objective: To determine diagnostic accuracy of CT-perfusion compared to complete clinical evaluation for NDD.

Secondary objectives: 1) To confirm the safety of performing CT-perfusion in critically ill patients suspected of being neurologically deceased; 2) To establish the CT-perfusion inter-rater reliability for NDD; 3) To evaluate the diagnostic accuracy of CT-angiography compared to complete clinical evaluation and to CT-perfusion for NDD; 4) To describe the clearance of commonly used sedatives and narcotics in the setting of NDD; and 5) to investigate biological changes (inflammatory and nanovesicles) that occur in humans during the brain dying process.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The investigators will conduct a large prospective Canadian multi-centre diagnostic cohort study. The primary diagnostic test evaluated will be CT-perfusion. The reference standard will be the complete clinical evaluation of brainstem functions. Comatose patients at high risk of neurological death exempt of confounding factors (e.g. hypothermic patients, use of long-acting sedatives, etc.) will be included. All patients will undergo CT-perfusion of the head (with CT-angiography reconstructions) followed by a complete NDD assessment. Both CT-perfusion and the clinical exam will be performed by independent assessors blinded from each others' interpretation. The primary endpoints will be the sensitivity and specificity of CT-perfusion to confirm NDD. Safety endpoints will be CT-perfusion -related adverse events (i.e. contrast-induced kidney injury, new hemodynamic instability while undergoing CT-perfusion). The true negative, true positive, false negative and false positive for CT-angiography obtained from the CT-perfusion source images when compared to the reference standard as well as when compared to the CT-Perfusion will also be reported. The sensitivity and specificity of CT-angiography compared to the reference standard and to CT-perfusion along with corresponding 95% confidence intervals will be calculated. Individual patient and population pharmacokinetics of analgesics and sedatives will be determined. To better investigate the impact of residual circulating sedative or narcotic levels on the accuracy of CT-Perfusion and CT-Angiography, Receiver Operating Characteristics (ROC) curves for varying levels of narcotic or sedative thresholds and compute the ROC area under the curve for each threshold will be plotted. To assess the immune phenotype, peripheral blood mononuclear cells activation will be evaluated by flow cytometry and cytokines by multiplex analyses. Nanovesicles fraction will be isolated from the plasma by ultracentrifugation and antigenic content and enzymatic activity. The plasma will finally be analysed by ELISAs and multiplex analyses to determine the levels of pro-inflammatory cytokines.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
333

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada
        • Foothills Medical Centre
    • Manitoba
      • Winnipeg, Manitoba, Canada
        • Winnipeg Health Sciences Centre
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
        • Queen Elizabeth II Health Sciences Centre
    • Ontario
      • Brampton, Ontario, Canada, L6R 3J7
        • William Osler Health System
      • Hamilton, Ontario, Canada
        • Hamilton Health Sciences Center
      • Kingston, Ontario, Canada
        • Kingston General Hospital
      • London, Ontario, Canada
        • London Health Sciences Centre
      • Ottawa, Ontario, Canada
        • The Ottawa Hospital
      • Toronto, Ontario, Canada
        • St-Michael's Hospital
    • Quebec
      • Montreal, Quebec, Canada
        • McGill University Health Centre
      • Montreal, Quebec, Canada
        • Centre hospitalier de l'Université de Montréal (CHUM)
      • Montreal, Quebec, Canada
        • Montreal Neurological Institute and Hospital
      • Quebec City, Quebec, Canada
        • CHU de Québec - Université Laval
      • Sherbrooke, Quebec, Canada
        • Centre Hospitalier Universitaire de Sherbrooke

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adults 18 years and older
  2. Admitted in the intensive care unit with a brain injury
  3. Glasgow Coma Scale (GCS) = 3
  4. Sedation stopped for at least 6 hours

Exclusion Criteria:

  1. Patients with the following contraindications to CT-perfusion will be excluded from the study:

    • Pregnancy
    • Contrast allergy
    • Clinician refuses inclusion because of kidney injury.

  2. Patients with any of the following confounding factors precluding complete clinical neurological evaluation will be excluded from the study:

    • Cervical fracture above C6
    • Significant facial trauma limiting cranial nerve examination
    • Hypothermia < 34 °C
    • Use of intravenous barbiturates at any time since admission
    • Unresuscitated shock
    • Peripheral nerve or muscle dysfunction or neuromuscular blockade potentially accounting for unresponsiveness
    • Anoxic brain injury < 24h (or 72h if therapeutic hypothermia)
    • Attending physician disagrees to conduct an apnea test
    • Any other abnormalities deemed a confounding factor for NDD by the attending clinician

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Neurological Diagnostic Evaluation
Exams performed according to a determined schedule following admission in the intensive care unit in order to validate CT-perfusion as an accurate ancillary test for neurological diagnostic.
Diagnostic test: Neurological Diagnostic Evaluation

Clinical Data:

  • Demographic data
  • Daily data (clinical exams, laboratory data)
  • Drug administration
  • Additional clinical or ancillary neurological determination test

Diagnostic Intervention:

  • CT-Perfusion
  • CT-Angiography reconstructions

Reference Standard:

- Clinical Neurological Exam

Blood Samples (Pharmacokinetics, Inflammatory & Nanovesicles Parameters):

  • At the time of patient enrolment
  • 6 hours after patient enrolment
  • At the time of the clinical neurological exam

Secondary Outcome measures at 6 months:

  • extended Glasgow Outcome Scale (GOSe)
  • modified Rankin Scale (mRS)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Accuracy of CT-perfusion
Time Frame: CT-Perfusion scan and clinical assessment must be less than 2 hours apart
Sensitivity and specificity for brainstem death of CT-perfusion compared to the clinical examination
CT-Perfusion scan and clinical assessment must be less than 2 hours apart

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Predictive Values
Time Frame: CT-Perfusion scan and clinical assessment must be less than 2 hours apart
Positive and negative predictive values between two independent neuroradiology interpretations of CT-perfusion for brainstem death
CT-Perfusion scan and clinical assessment must be less than 2 hours apart
Likelihood Ratios
Time Frame: CT-Perfusion scan and clinical assessment must be less than 2 hours apart
Positive and negative likelihood ratios between two independent neuroradiology interpretations of CT-perfusion for brainstem death
CT-Perfusion scan and clinical assessment must be less than 2 hours apart
Inter-rater Agreement
Time Frame: CT-Perfusion scan and clinical assessment must be less than 2 hours apart
Between two independent neuroradiology interpretations of CT-perfusion for brainstem death
CT-Perfusion scan and clinical assessment must be less than 2 hours apart
Volume of Distribution
Time Frame: 48 hours
Volume of distribution from serum concentrations and drug dosing history
48 hours
Clearance
Time Frame: 48 hours
Volume of plasma completely cleared of the drug expressed as mL/min
48 hours
Elimination Rate Constant
Time Frame: 48 hours
Rate at which the drug is removed from the body
48 hours
Concentration-time Curve
Time Frame: 48 hours
Concentration of drug versus time
48 hours
Accuracy of CT-perfusion at 6 Months
Time Frame: 6 months
Sensitivity and specificity for brainstem death of CT-perfusion compared to the clinical examination for a good mRS score (3 or less) at 6 months
6 months
Accuracy of the Predictive Values at 6 Months
Time Frame: 6 months
Positive and negative predictive values between two independent neuroradiology interpretations of CT-perfusion for brainstem death for a good mRS score (3 or less) at 6 months
6 months
Accuracy of the Likelihood Ratios at 6 Months
Time Frame: 6 months
Positive and negative likelihood ratios between two independent neuroradiology interpretations of CT-perfusion for brainstem death for a good mRS score (3 or less) at 6 months
6 months
Accuracy of the Inter-rater Agreement at 6 Months
Time Frame: 6 months
Between two independent neuroradiology interpretations of CT-perfusion for brainstem death for a good mRS score (3 or less) at 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Centre hospitalier de l'Université de Montréal (CHUM)

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Canadian Institutes of Health Research (CIHR)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Michael Chassé, MD PhD FRCPC, Centre hospitalier de l'Université de Montréal (CHUM)
  • Principal Investigator: Jai JS Shankar, MD MSc FRCPC, University of Manitoba

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 25, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 22, 2021

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 22, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 27, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 31, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 23, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 22, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CE 16.379

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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