Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04318665 |
| Other study ID # |
HS23683 (B2020:018) |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 23, 2020 |
| Est. completion date |
August 2, 2023 |
Study information
| Verified date |
January 2024 |
| Source |
University of Manitoba |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
