Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000071628
Ethics application status
Approved
Date submitted
15/01/2014
Date registered
21/01/2014
Date last updated
15/06/2021
Date data sharing statement initially provided
15/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Therapeutic Hypothermia in Acute Ischemic Stroke (THAIS)
Scientific title
A randomized controlled trial in ischemic stroke patients with successful endovascular recanalization of therapeutic hypothermia versus standard care using radiological stroke growth as primary outcome and secondary clinical outcomes
Secondary ID [1] 283910 0
nil
Universal Trial Number (UTN)
Trial acronym
THAIS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ischemic Stroke 290907 0
Condition category
Condition code
Stroke 291260 291260 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Therapeutic hypothermia - cooling to 33deg C for 48hr using initial chilled intravenous saline and maintenance external cooling blankets. Subsequent slow rewarming over ~12hr regulated by the blanket.
Intervention code [1] 288592 0
Treatment: Devices
Intervention code [2] 288621 0
Treatment: Other
Comparator / control treatment
Standard guideline-based stroke unit care
Control group
Active

Outcomes
Primary outcome [1] 291257 0
Absolute growth in diffusion MRI lesion volume between initial (post-endovascular therapy) and 3-5 day MRI, adjusted for baseline volume.
Timepoint [1] 291257 0
Day 3-5 post stroke onset
Secondary outcome [1] 306360 0
correlation of infarct growth with “area under curve” of the temperature actually achieved (measured using tympanic infrared thermometer) during the 48hr of hypothermia
Timepoint [1] 306360 0
Day 3-5 post stroke onset
Secondary outcome [2] 306361 0
median change in National Institutes of Health Stroke Scale (NIHSS) from baseline to day 3-5
Timepoint [2] 306361 0
Day 3-5 post stroke onset
Secondary outcome [3] 306363 0
median change in National Institutes of Health Stroke Scale (NIHSS) from baseline to day 90
Timepoint [3] 306363 0
Day 90 post-stroke onset
Secondary outcome [4] 306364 0
ordinal analysis of the modified Rankin Scale (mRS) at day 90
Timepoint [4] 306364 0
Day 90 post stroke onset
Secondary outcome [5] 306366 0
Symptomatic intracerebral hemorrhage (blood clot with mass effect occupying >30% of the infarcted area on CT or MRI, combined with >=4 point increase in NIHSS score, occurring <36hr post-treatment)
Timepoint [5] 306366 0
3-5 days post stroke onset
Secondary outcome [6] 306367 0
Radiologically confirmed pneumonia
Timepoint [6] 306367 0
At any time during study period (90 days)

Eligibility
Key inclusion criteria
Patients with ischaemic stroke who have undergone successful (TICI 2b/3) endovascular recanalization and are being cared for in intensive care

Informed consent from patient, person responsible or procedural authorization as approved by HREC

Possibility to start hypothermia within 6 hours of stroke onset
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Metallic foreign bodies or severe claustrophobia precluding MRI
Severe co-morbidity or dementia (pre-stroke modified Rankin Scale 4-5)
Clinical diagnosis of pneumonia or other sepsis at baseline
Bradycardia <40bpm at baseline
Skin damage (e.g., inflammation, burns, injuries, ulcerations, hives, rash) at the sites intended to be used for cooling
Contraindication to sedation and intubation
Current participation in another interventional clinical trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Following consent, a sealed randomization envelope appropriate for the patient stratum (infratentorial or supratentorial stroke) will be opened to reveal the allocation to therapeutic hypothermia or standard care.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random number generator (Excel), block randomized in 2 strata.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
There will be two strata – infratentorial (vertebrobasilar +/- PCA territories) and supratentorial stroke. The primary outcome will be the absolute growth in diffusion MRI lesion volume between initial (post-endovascular therapy) and 3-5 day MRI, adjusted for baseline volume (median regression analysis). The volumetric measurement of diffusion MRI lesions will be performed by a blinded investigator. Given the lack of data to estimate effect size we have calculated sample size based on precision estimates. The standard deviation of absolute growth measures in similar patients (EPITHET study) was approximately 20mL. With 16 patients in each arm of the study, the 95% confidence interval for the difference in infarct growth would be +/- 10mL which we believe to be reasonable precision for this study.
Secondary safety outcomes include symptomatic intracerebral hemorrhage (blood clot with mass effect occupying >30% of infarcted territory (PH2) associated with =4 point increase in NIHSS occurring within 36hr of treatment) and radiologically confirmed pneumonia. Exploratory analyses will include correlation of infarct growth with “area under curve” of the temperature actually achieved during the 48hr of hypothermia, median change in NIHSS from baseline to day 3-5 and day 90 and ordinal analysis of the mRS at day 90 for the purposes of power calculation for future studies.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
22/01/2014
Actual
22/09/2015
Date of last participant enrolment
Anticipated
Actual
13/07/2019
Date of last data collection
Anticipated
22/01/2019
Actual
13/07/2019
Sample size
Target
32
Accrual to date
Final
4
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1969 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 7701 0
3050 - Royal Melbourne Hospital

Funding & Sponsors
Funding source category [1] 288550 0
Hospital
Name [1] 288550 0
Department of Neurology, Royal Melbourne Hospital
Country [1] 288550 0
Australia
Primary sponsor type
Hospital
Name
Royal Melbourne Hospital
Address
Grattan St
Parkville VIC 3050
Country
Australia
Secondary sponsor category [1] 287262 0
None
Name [1] 287262 0
Address [1] 287262 0
Country [1] 287262 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290414 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 290414 0
Royal Melbourne Hospital
Grattan St
Parkville VIC 3050
Ethics committee country [1] 290414 0
Australia
Date submitted for ethics approval [1] 290414 0
Approval date [1] 290414 0
09/01/2014
Ethics approval number [1] 290414 0
2013.300

Summary
Brief summary
Hypothermia has great promise as a cytoprotective therapy after stroke given clinical benefit in other brain injury scenarios and animal models of stroke. THAIS is a pilot randomized trial of hypothermia (cooling) versus standard care that focuses on patients with major stroke who have undergone rapid, successful recanalization. This group often demonstrates initial improvement in brain imaging (diffusion MRI) followed by later re-appearance of the lesion which likely reflects a secondary injury. If hypothermia can reduce this secondary injury it has great potential to improve patient outcomes after severe stroke – a patient group that currently have very few treatment options.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 45570 0
Dr Bruce Campbell
Address 45570 0
Dept Neurology
Royal Melbourne Hospital
Grattan St
Parkville VIC 3050
Country 45570 0
Australia
Phone 45570 0
+61 3 9342 7000
Fax 45570 0
+61 3 9342 8427
Email 45570 0
[email protected]
Contact person for public queries
Name 45571 0
Dr Bruce Campbell
Address 45571 0
Dept Neurology
Royal Melbourne Hospital
Grattan St
Parkville VIC 3050
Country 45571 0
Australia
Phone 45571 0
+61 3 9342 7000
Fax 45571 0
+61 3 9342 8427
Email 45571 0
[email protected]
Contact person for scientific queries
Name 45572 0
Dr Bruce Campbell
Address 45572 0
Dept Neurology
Royal Melbourne Hospital
Grattan St
Parkville VIC 3050
Country 45572 0
Australia
Phone 45572 0
+61 3 9342 7000
Fax 45572 0
+61 3 9342 8427
Email 45572 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.