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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03098511
Recruitment Status : Active, not recruiting
First Posted : March 31, 2017
Last Update Posted : February 24, 2022
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Centre hospitalier de l'Université de Montréal (CHUM)

Tracking Information
First Submitted Date  ICMJE March 22, 2017
First Posted Date  ICMJE March 31, 2017
Last Update Posted Date February 24, 2022
Actual Study Start Date  ICMJE April 25, 2017
Estimated Primary Completion Date September 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2017)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2017)
  • 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
  • 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
  • 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
  • Volume of Distribution [ Time Frame: 48 hours ]
    Volume of distribution from serum concentrations and drug dosing history
  • Clearance [ Time Frame: 48 hours ]
    Volume of plasma completely cleared of the drug expressed as mL/min
  • Elimination Rate Constant [ Time Frame: 48 hours ]
    Rate at which the drug is removed from the body
  • Concentration-time Curve [ Time Frame: 48 hours ]
    Concentration of drug versus time
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CT-Perfusion for Neurological Diagnostic Evaluation
Official Title  ICMJE CT-Perfusion for Neurological Diagnostic Evaluation: a Prospective Canadian Multicenter Diagnostic Test Study
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:
  1. Participant will be comatose
  2. Care providers, investigators and outcome assessors will be blinded from the results of the CT-Perfusion scan result (for the clinical assessment) and from the clinical assessment results (for the CT-Perfusion scan interpretation)
Primary Purpose: Diagnostic
Condition  ICMJE Neurological Determination of Death
Intervention  ICMJE 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)
Study Arms  ICMJE 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.
Intervention: Diagnostic Test: Neurological Diagnostic Evaluation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 23, 2021)
333
Original Estimated Enrollment  ICMJE
 (submitted: March 27, 2017)
300
Estimated Study Completion Date  ICMJE September 1, 2022
Estimated Primary Completion Date September 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03098511
Other Study ID Numbers  ICMJE CE 16.379
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Centre hospitalier de l'Université de Montréal (CHUM)
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Centre hospitalier de l'Université de Montréal (CHUM)
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Canadian Institutes of Health Research (CIHR)
Investigators  ICMJE
Principal Investigator: Michaël Chassé, MD PhD FRCPC Centre hospitalier de l'Université de Montréal (CHUM)
Principal Investigator: Jai JS Shankar, MD MSc FRCPC University of Manitoba
PRS Account Centre hospitalier de l'Université de Montréal (CHUM)
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP