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Early Diagnosis of Mortality Using Admission CT Perfusion in Severe Traumatic Brain Injury Patients (ACT-TBI Study) (ACT-TBI)

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ClinicalTrials.gov Identifier: NCT04318665
Recruitment Status : Not yet recruiting
First Posted : March 24, 2020
Last Update Posted : March 30, 2020
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Jai Shankar, University of Manitoba

Tracking Information
First Submitted Date  ICMJE March 20, 2020
First Posted Date  ICMJE March 24, 2020
Last Update Posted Date March 30, 2020
Estimated Study Start Date  ICMJE June 2020
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 26, 2020)
The primary outcome is a binary outcome of mortality ('dead') or survival ('not-dead') in the first 48 hours of hospital admission. [ Time Frame: 48 hours ]
The primary outcome of this study is determining the mortality ('dead') or survival ('not-dead') in the first 48 hours of hospital admission using CTP.
Original Primary Outcome Measures  ICMJE
 (submitted: March 20, 2020)
The primary outcome is a binary outcome of mortality ('dead') or survival ('not-dead') in the first 48 hrs of hospital admission. [ Time Frame: 48 hrs ]
The primary outcome of this study is determining the mortality ('dead') or survival ('not-dead') in the first 48 hrs of hospital admission using CTP.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2020)
In-hospital mortality at the end of hospital discharge. [ Time Frame: 6 months ]
the secondary outcome of this study is to determine In-hospital mortality at the end of hospital discharge.
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 Early Diagnosis of Mortality Using Admission CT Perfusion in Severe Traumatic Brain Injury Patients (ACT-TBI Study)
Official Title  ICMJE Early Diagnosis of Mortality Using Admission CT Perfusion in Severe Traumatic Brain Injury Patients (ACT-TBI Study)
Brief Summary

Background: Severe traumatic brain injury (TBI) is a principal cause of post-injury hospitalization, disability, and death throughout the world. TBI is the leading cause of death and disability among young healthy people under 45 years of age and is predicted to be the most prevalent and costliest neurological condition in Canada through the year 2031.

TBI is commonly classified into mild, moderate, and severe categories using the Glasgow Coma Scale (GCS), with "severe TBI" defined as a GCS score ≤ 8. Severe TBI is a clinical emergency, during which the trauma team works swiftly to provide the appropriate care. Outcome assessment after TBI is complex and is influenced by pre-injury and injury factors as well as the patient's response at various stages of recovery. The first 48 hrs in hospital, despite being the most resource-intensive period, unfortunately result in the highest mortality. These patients are on life support at the time of their hospital admission and adequate and reliable clinical examination is impossible. Thus, patients receive treatment despite lack of a clear understanding of their prognoses.

Hypothesis: Admission Computed Tomographic Perfusion (CTP) can diagnose brain death reliably in severe TBI patients in early stage upon hospital admission, which is not recognised in the usual clinical practice due to inadequate reliable clinical examination. In a small prospective pilot study of 19 patients with severe TBI, admission CTP could predict early in hospital mortality with 75% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 94% negative predictive value (NPV) and perfect inter-rater reliability (kappa=1). We propose ACT-TBI study to evaluate CTP as a triage tool to diagnose early mortality at the time of admission in patients with severe TBI.

Primary Objective: To validate admission CTP features of brain death, relative to the clinical examination outcome, for characterizing early in-hospital mortality.

Secondary objectives: To establish the safety and interrater reliability of admission CTP.

Detailed Description

Objectives of the ACT-TBI study:

In patients with severe TBI,

  1. To validate admission CTP features of brain death, relative to the clinical examination outcome, for characterizing early in-hospital mortality.
  2. To establish the safety and inter-rater reliability of features of brain death on admission CTP.
  3. To evaluate the determinants (age, sex, and GCS score) influencing the variability in response of CTP.
  4. To establish the usefulness of CTP in facilitating timely organ transplantation, if possible.

Research Design and Method The ACT-TBI study is a prospective, multi-centre, cohort study in patients with severe TBI and will be conducted in 4 different Canadian centres (Winnipeg, Ottawa, Montreal, and Halifax) over the next 4 years.

Those patients meeting eligibility criteria will be identified by a dedicated research nurse with the help of the trauma team at the time of hospital admission, with the ACT-TBI study protocol will be activated at the time of their first diagnostic imaging. A deferral of consent will be obtained like that in the pilot study.

Clinical Examination- The results of initial clinical, laboratory and imaging assessment will be recorded as per the IMPACT (International Mission for Prognosis and Analysis of Clinical Trials in TBI) core and extended models. The clinical examination will occur during a sedation hold, when possible acknowledging some confounding from effect of residual sedation.

Radiological Examinations Upon hospital admission, at the time of initial diagnostic imaging, besides the standard diagnostic tests of whole-body CT scan, enrolled patients will undergo the whole head imaging protocol with CTP.

Plain computed tomography (CT) of head: As a standard imaging protocol, plain CT of head will be performed for severe TBI patients. These images will be assessed for the presence of various lesions (subarachnoid hemorrhage, sub-dural hemorrhage, epidural hemorrhage, intra-ventricular hemorrhage, cerebral contusions, and edema).

Computed tomography perfusion (CTP): Besides, a standard imaging protocol, CTP imaging protocol for whole head will be performed. Images will be acquired following our previously published protocol. In brief, a total of 40 mL of CT contrast media will be injected at a rate of 5 mL/sec. A set of axial images with a slice thickness of 5 mm for the perfusion analysis will be reconstructed. CTP images will only be acquired. The anonymized images will be transferred and stored in the secured imaging core lab, department of Radiology, University of Manitoba, for processing and interpretation later. CTP will be processed using a semiautomatic deconvolution algorithm on a vendor neutral software package (Oleasphere). CTP will be assessed both quantitatively as well as qualitatively.

  • Quantitative assessment: brain death will be defined as Cerebral Blood Flow (CBF) <5 mL/100g/min and Cerebral Blood Volume (CBV) <2 mL/100g in the brainstem.
  • Qualitative assessment: brain death will be defined as matched decrease of CBF and CBV in the brainstem. The perfusion maps for CBF and CBV will be assessed for binary outcome of 'dead' or 'not-dead', according to our previously published methods.

The perfusion images will be assessed by the two independent neuroradiologists, who are blinded to the clinical status of the patient and also to each other's assessment. In case of disagreement, the expert neuroradiologist opinion will be employed to have a consensus agreement for the final analysis.

Post-perfusion care: Since the prognostic value of CTP has not been established in patients with severe TBI, the outcomes of CTP will not be made available to the clinical team involved in patient care. All patients will receive the standard care.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Traumatic Brain Injury
Intervention  ICMJE Diagnostic Test: CT Perfusion
Severe Traumatic Brain Injury patients will be undergoing CT perfusion test
Study Arms  ICMJE Experimental: CT Perfusion
Severe TBI patients will be undergoing CT perfusion test
Intervention: Diagnostic Test: CT Perfusion
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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: March 20, 2020)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • At least 18 years old
  • Severe head injury with the activation of the trauma code
  • GCS score ≤ 8 after initial resuscitation
  • On mechanical respiratory ventilation at the time of imaging

Exclusion Criteria:

  • No known GCS after initial resuscitation
  • Known pregnancy
  • Known contraindication to CT contrast agent, e.g.,allergy or anaphylactic reaction
  • Known end-stage renal disease stage 4-5 (eGFR < 30 mL/min/1.73 m2)
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: Jai Shankar, MD FRCPC 431 373 4164 shivajai1@gmail.com
Contact: Sudharsana R Ande, PhD 204 789 3996 sudarshanande@yahoo.com
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04318665
Other Study ID Numbers  ICMJE HS23683 (B2020:018)
Has Data Monitoring Committee No
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
Responsible Party Jai Shankar, University of Manitoba
Study Sponsor  ICMJE University of Manitoba
Collaborators  ICMJE Canadian Institutes of Health Research (CIHR)
Investigators  ICMJE
Principal Investigator: Jai Shankar, MD FRCPC University of Manitoba
Principal Investigator: Frederick Zeiler, MD FRCPC University of Manitoba
PRS Account University of Manitoba
Verification Date March 2020

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