Neurological Determination of DeathINDex-CTPNCT03098511
CT-Perfusion for Neurological Diagnostic Evaluation
A study testing Neurological Diagnostic Evaluation in people with Neurological Determination of Death, run by Centre hospitalier de l'Université de Montréal (CHUM) at 14 sites in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neurological Determination of Death
- What is being tested?
- Neurological Diagnostic Evaluation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 333 participants
- Where
- 14 sitesCanada
- Study dates
- 25 Apr 2017to 31 Aug 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults 18 years and older
- Admitted in the intensive care unit with a brain injury
- Glasgow Coma Scale (GCS) = 3
- Sedation stopped for at least 6 hours
Who cannot join
- Patients with the following contraindications to CT-perfusion will be excluded from the study:
- Pregnancy
- Contrast allergy
- Clinician refuses inclusion because of kidney injury.
- Patients with any of the following confounding factors precluding complete clinical neurological evaluation will be excluded from the study:
- Cervical fracture above C6
Show all 14Show fewer
- 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
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
Canada14 sites
William Osler Health System
Brampton, Ontario, L6R 3J7
Foothills Medical Centre
Calgary, Alberta
Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia
Hamilton Health Sciences Center
Hamilton, Ontario
Kingston General Hospital
Kingston, Ontario
London Health Sciences Centre
London, Ontario
Centre Hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec
McGill University Health Centre
Montreal, Quebec
Montreal Neurological Institute and Hospital
Montreal, Quebec
The Ottawa Hospital
Ottawa, Ontario
CHU de Québec - Université Laval
Québec, Quebec
Centre Hospitalier Universitaire de Sherbrooke
Sherbrooke, Quebec
St-Michael's Hospital
Toronto, Ontario
Winnipeg Health Sciences Centre
Winnipeg, Manitoba
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Neurological Determination of Death
- Being tested
- Neurological Diagnostic Evaluation
- Keywords
- Neurological Determination of Death, Determination of Death, CT-Perfusion scan, Ancillary Test, Organ Donation
- Medical subject headings
- Death
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neurological Diagnostic EvaluationDiagnostic test
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)
| Study group | Role | What they receive |
|---|---|---|
| Neurological Diagnostic Evaluation | Other | 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. Receives: Diagnostic Test: Neurological Diagnostic Evaluation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Accuracy of CT-perfusion
Sensitivity and specificity for brainstem death of CT-perfusion compared to the clinical examination
Measured: CT-Perfusion scan and clinical assessment must be less than 2 hours apart
Secondary outcomes (11)
Predictive Values
Positive and negative predictive values between two independent neuroradiology interpretations of CT-perfusion for brainstem death
Measured: CT-Perfusion scan and clinical assessment must be less than 2 hours apart
Likelihood Ratios
Positive and negative likelihood ratios between two independent neuroradiology interpretations of CT-perfusion for brainstem death
Measured: CT-Perfusion scan and clinical assessment must be less than 2 hours apart
Inter-rater Agreement
Between two independent neuroradiology interpretations of CT-perfusion for brainstem death
Measured: CT-Perfusion scan and clinical assessment must be less than 2 hours apart
Volume of Distribution
Volume of distribution from serum concentrations and drug dosing history
Measured: 48 hours
Clearance
Volume of plasma completely cleared of the drug expressed as mL/min
Measured: 48 hours
Elimination Rate Constant
Rate at which the drug is removed from the body
Measured: 48 hours
Concentration-time Curve
Concentration of drug versus time
Measured: 48 hours
Accuracy of CT-perfusion at 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
Measured: 6 months
Accuracy of the Predictive Values at 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
Measured: 6 months
Accuracy of the Likelihood Ratios at 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
Measured: 6 months
Accuracy of the Inter-rater Agreement at 6 Months
Between two independent neuroradiology interpretations of CT-perfusion for brainstem death for a good mRS score (3 or less) at 6 months
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2017
- Study start25 Apr 2017
- Primary completion22 Feb 2021
- Study completion31 Aug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neurological Determination of DeathStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 333 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Michaël Chassé, MD PhD FRCPC, Principal investigator, Centre hospitalier de l'Université de Montréal (CHUM)Jai JS Shankar, MD MSc FRCPC, Principal investigator, University of Manitoba
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03098511
- Sponsor's protocol ID
- CE 16.379
- Acronym
- INDex-CTP
- Status last verified
- Apr 2024
- First submitted
- 22 Mar 2017
- Last updated
- 23 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Neves Briard J, English SW, Fergusson DA, Dhanani S, Lauzier F, Turgeon AF, Ball I, Darvesh S, Titova P, Lebrasseur M, Couillard P, Kramer A, D'Aragon F, Hannouche M, Burns KEA, Boyd JG, Binnie A, Wang HT, Shemie S, Shankar JJS, Chasse M; INDex Investigators and The Canadian Critical Care Trials Group. Prevalence, semiology and neuroimaging of movements in comatose adults at risk of death by neurologic criteria: a prospective cohort study. Crit Care. 2026 May 14;30(1):362. doi: 10.1186/s13054-026-06037-2.
PubMed 42135815
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CT-Perfusion for Neurological Diagnostic Evaluation: a Prospective Canadian Multicenter Diagnostic Test Study
- ClinicalTrials.gov ID
- NCT03098511
- Acronym / sponsor ID
- INDex-CTP / CE 16.379
- Conditions
- Neurological Determination of Death
- Keywords
- Neurological Determination of Death, Determination of Death, CT-Perfusion scan, Ancillary Test, Organ Donation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 333 participants (actual)
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- 25 Apr 2017 (actual)
- Primary completion
- 22 Feb 2021 (actual)
- Study completion
- 31 Aug 2024 (estimated)
- First posted
- 31 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neurological Diagnostic Evaluation | Other | Diagnostic Test: Neurological Diagnostic EvaluationExams 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adults 18 years and older
- Admitted in the intensive care unit with a brain injury
- Glasgow Coma Scale (GCS) = 3
- Sedation stopped for at least 6 hours
Key exclusion criteria (14 listed)
- Patients with the following contraindications to CT-perfusion will be excluded from the study:
- Patients with any of the following confounding factors precluding complete clinical neurological evaluation will be excluded from the study:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neurological Diagnostic EvaluationClinical 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) | Diagnostic test | Neurological Diagnostic Evaluation |
Primary outcome
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
11 secondary outcomes
Predictive Values
Time frame: 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
Inter-rater Agreement
Time frame: CT-Perfusion scan and clinical assessment must be less than 2 hours apart
Volume of Distribution
Time frame: 48 hours
Clearance
Time frame: 48 hours
Elimination Rate Constant
Time frame: 48 hours
Concentration-time Curve
Time frame: 48 hours
Accuracy of CT-perfusion at 6 Months
Time frame: 6 months
Accuracy of the Predictive Values at 6 Months
Time frame: 6 months
Accuracy of the Likelihood Ratios at 6 Months
Time frame: 6 months
Accuracy of the Inter-rater Agreement at 6 Months
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2024.
- Derived from this study: PubMed 42135815Neves Briard J, English SW, Fergusson DA, Dhanani S, Lauzier F, Turgeon AF, Ball I, Darvesh S, Titova P, Lebrasseur M, Couillard P, Kramer A, D'Aragon F, Hannouche M, Burns KEA, Boyd JG, Binnie A, Wang HT, Shemie S, Shankar JJS, Chasse M; INDex Investigators and The Canadian Critical Care Trials Group. Prevalence, semiology and neuroimaging of movements in comatose adults at risk of death by neurologic criteria: a prospective cohort study. Crit Care. 2026 May 14;30(1):362. doi: 10.1186/s13054-026-06037-2.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michaël Chassé, MD PhD FRCPC principal investigator
Centre hospitalier de l'Université de Montréal (CHUM)
Jai JS Shankar, MD MSc FRCPC principal investigator
University of Manitoba
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Neurological Diagnostic Evaluation in people with Neurological Determination of Death, run by Centre hospitalier de l'Université de Montréal (CHUM) at 14 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Accuracy of CT-perfusion (time frame: CT-Perfusion scan and clinical assessment must be less than 2 hours apart). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03098511, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2024.