Neurological Determination of Death Clinical Trial
— INDex-CTPOfficial title:
CT-Perfusion for Neurological Diagnostic Evaluation: a Prospective Canadian Multicenter Diagnostic Test Study
| Verified date | April 2024 |
| Source | Centre hospitalier de l'Université de Montréal (CHUM) |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 333 |
| Est. completion date | August 31, 2024 |
| Est. primary completion date | February 22, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Canada | William Osler Health System | Brampton | Ontario |
| Canada | Foothills Medical Centre | Calgary | Alberta |
| Canada | Queen Elizabeth II Health Sciences Centre | Halifax | Nova Scotia |
| Canada | Hamilton Health Sciences Center | Hamilton | Ontario |
| Canada | Kingston General Hospital | Kingston | Ontario |
| Canada | London Health Sciences Centre | London | Ontario |
| Canada | Centre Hospitalier de l'Université de Montréal (CHUM) | Montreal | Quebec |
| Canada | McGill University Health Centre | Montreal | Quebec |
| Canada | Montreal Neurological Institute and Hospital | Montreal | Quebec |
| Canada | The Ottawa Hospital | Ottawa | Ontario |
| Canada | CHU de Québec - Université Laval | Quebec City | Quebec |
| Canada | Centre Hospitalier Universitaire de Sherbrooke | Sherbrooke | Quebec |
| Canada | St-Michael's Hospital | Toronto | Ontario |
| Canada | Winnipeg Health Sciences Centre | Winnipeg | Manitoba |
| Lead Sponsor | Collaborator |
|---|---|
| Centre hospitalier de l'Université de Montréal (CHUM) | Canadian Institutes of Health Research (CIHR) |
Canada,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Accuracy of CT-perfusion | 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 | Predictive Values | 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 | |
| Secondary | Likelihood Ratios | 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 | |
| Secondary | Inter-rater Agreement | Between two independent neuroradiology interpretations of CT-perfusion for brainstem death | CT-Perfusion scan and clinical assessment must be less than 2 hours apart | |
| Secondary | Volume of Distribution | Volume of distribution from serum concentrations and drug dosing history | 48 hours | |
| Secondary | Clearance | Volume of plasma completely cleared of the drug expressed as mL/min | 48 hours | |
| Secondary | Elimination Rate Constant | Rate at which the drug is removed from the body | 48 hours | |
| Secondary | Concentration-time Curve | Concentration of drug versus time | 48 hours | |
| Secondary | 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 | 6 months | |
| Secondary | 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 | 6 months | |
| Secondary | 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 | 6 months | |
| Secondary | 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 | 6 months |