Traumatic Brain InjuryACT-TBINCT04318665
Early Diagnosis of Mortality Using Admission CT Perfusion in Severe Traumatic Brain Injury Patients (ACT-TBI Study)
A study testing CT Perfusion in people with Traumatic Brain Injury, run by University of Manitoba at 4 sites in Canada.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- CT Perfusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 4 sitesCanada
- Study dates
- 23 Jul 2020to 2 Aug 2023
- 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
- 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
Who cannot join
- 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)
Trial locations and contacts
4 sites in 1 country.
Canada4 sites
QEII Health Scienecs Centre
Halifax, Nova Scotia, B3K 4N1
Centre hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, H2X 0C1
The Ottawa Hospital
Ottawa, Ontario, K1Y 4E9
Health Sciences Centre
Winnipeg, Manitoba, R3A 1R9
About this study
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.
Read more
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.
Read the detailed description
Objectives of the ACT-TBI study:
In patients with severe TBI,
- To validate admission CTP features of brain death, relative to the clinical examination outcome, for characterizing early in-hospital mortality.
- To establish the safety and inter-rater reliability of features of brain death on admission CTP.
- To evaluate the determinants (age, sex, and GCS score) influencing the variability in response of CTP.
- 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.
- Conditions
- Traumatic Brain Injury
- Being tested
- CT Perfusion
- Keywords
- TBI, CTP
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CT PerfusionDiagnostic test
Severe Traumatic Brain Injury patients will be undergoing CT perfusion test
| Study group | Role | What they receive |
|---|---|---|
| CT Perfusion | Experimental | Severe TBI patients will be undergoing CT perfusion test Receives: Diagnostic Test: CT Perfusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome is a binary outcome of mortality ('dead') or survival ('not-dead') in the first 48 hours of hospital admission.
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.
Measured: 48 hours
Secondary outcomes (1)
In-hospital mortality at the end of hospital discharge.
the secondary outcome of this study is to determine In-hospital mortality at the end of hospital discharge.
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 posted24 Mar 2020
- Study start23 Jul 2020
- Primary completion2 Aug 2023
- Study completion2 Aug 2023
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 Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by University of ManitobaThe sponsor's other registered studies.
- 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
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Manitoba
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Principal investigator, Jai Shankar, University of Manitoba
- Investigators
- Jai Shankar, MD FRCPC, Principal investigator, University of ManitobaFrederick Zeiler, MD FRCPC, Principal investigator, University of Manitoba
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04318665
- Sponsor's protocol ID
- HS23683 (B2020:018)
- Acronym
- ACT-TBI
- Status last verified
- Jan 2024
- First submitted
- 20 Mar 2020
- Last updated
- 19 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Alcock S, Batoo D, Ande SR, Grierson R, Essig M, Martin D, Trivedi A, Sinha N, Leeies M, Zeiler FA, Shankar JJS. Early diagnosis of mortality using admission CT perfusion in severe traumatic brain injury patients (ACT-TBI): protocol for a prospective cohort study. BMJ Open. 2021 Jun 9;11(6):e047305. doi: 10.1136/bmjopen-2020-047305.
PubMed 34108167
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Diagnosis of Mortality Using Admission CT Perfusion in Severe Traumatic Brain Injury Patients (ACT-TBI Study)
- ClinicalTrials.gov ID
- NCT04318665
- Acronym / sponsor ID
- ACT-TBI / HS23683 (B2020:018)
- Conditions
- Traumatic Brain Injury
- Keywords
- TBI, CTP
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- University of ManitobaUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- 23 Jul 2020 (actual)
- Primary completion
- 2 Aug 2023 (actual)
- Study completion
- 2 Aug 2023 (actual)
- First posted
- 24 Mar 2020 (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.
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,
- To validate admission CTP features of brain death, relative to the clinical examination outcome, for characterizing early in-hospital mortality.
- To establish the safety and inter-rater reliability of features of brain death on admission CTP.
- To evaluate the determinants (age, sex, and GCS score) influencing the variability in response of CTP.
- 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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CT Perfusion | Experimental | Diagnostic Test: CT PerfusionSevere TBI patients will be undergoing CT perfusion test |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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)
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 |
|---|---|---|
| CT PerfusionSevere Traumatic Brain Injury patients will be undergoing CT perfusion test | Diagnostic test | CT Perfusion |
Primary outcome
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.
1 secondary outcome
In-hospital mortality at the end of hospital discharge.
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2024.
- Derived from this study: PubMed 34108167Alcock S, Batoo D, Ande SR, Grierson R, Essig M, Martin D, Trivedi A, Sinha N, Leeies M, Zeiler FA, Shankar JJS. Early diagnosis of mortality using admission CT perfusion in severe traumatic brain injury patients (ACT-TBI): protocol for a prospective cohort study. BMJ Open. 2021 Jun 9;11(6):e047305. doi: 10.1136/bmjopen-2020-047305.
- 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.
Jai Shankar, MD FRCPC principal investigator
University of Manitoba
Frederick Zeiler, MD FRCPC principal investigator
University of Manitoba
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CT Perfusion in people with Traumatic Brain Injury, run by University of Manitoba at 4 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 4 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: finished, as of the sponsor's last update on 19 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
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). 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 NCT04318665, 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 19 Jan 2024.