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Trial registered on ANZCTR


Registration number
ACTRN12609000690257
Ethics application status
Approved
Date submitted
7/08/2009
Date registered
12/08/2009
Date last updated
9/12/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Cerebral Hypothermia in Ischaemic lesion (CHIL) Trial - A Randomised trial evaluating systemic and local mild hypothermia in Acute Ischaemic Stroke
Scientific title
The Cerebral Hypothermia in Ischaemic lesion (CHIL) Trial - A Randomised trial evaluating systemic and local mild hypothermia on infarct expansion and salvage of the ischaemic penumbra in Acute Ischaemic Stroke
Secondary ID [1] 288113 0
Nil
Universal Trial Number (UTN)
Trial acronym
CHIL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Ischaemic Stroke 243474 0
Condition category
Condition code
Stroke 239776 239776 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Systemic hypothermia is accomplished by an initial rapid infusion of 30ml per kg of ice-cold Hartmann's solution into a 16 guage peripheral intravenous catheter at 100 ml per minute, using a pressure bag. The target temperature of 33 degrees is achieved within about 30 minutes. Hypothermia is maintained by the use of a Therapeutic Goods Association approved endovascular cooling catheter which is inserted into the femoral vein and positioned with the catheter tip in the Inferior Vena Cava below the diaphragm. The endovascular cooling catheters use a heat exchange element within which circulates chilled sterile 0.9% saline within a closed internal circulatory system. The patient's rectal core temperature is monitored and provides a feedback system to the cooling system to maintain target temperature and control rewarming. the patient is cooled at 33 degrees for 24 hours and is rewarmed slowly to 37 degrees over 12 hours.
Intervention code [1] 237093 0
Treatment: Devices
Intervention code [2] 237094 0
Treatment: Other
Comparator / control treatment
Participants who are randomised to normothermia receive active routine care in the Acute Stroke Unit. Temperature is to be kept less than 38 degrees as per usual treatment post acute stroke.
Control group
Active

Outcomes
Primary outcome [1] 240542 0
Infarct expansion and penumbral salvage: Mean percent penumbral salvage from baseline computerised tomography (CT)scan confirming acute Middle Cerebral Artery Ischaemic stroke to 30 day computerised tomography scan, hypothermia versus normothermia groups. Penumbral salvage is defined as tissue salvaged/tissue at risk in terms of lesion volume.
Timepoint [1] 240542 0
Baseline CT scan and clinical assessment is attended on patients when first admitted to the emergency department. The CT scan is repeated 30 days post stroke to observe the outcome. The participant clinical outcome follow-up measures are attended 90 days post stroke.
Secondary outcome [1] 257118 0
Safety and Clinical: Mortality, neurological deterioration as measured by a decline in the National Institute of Health Stroke Scale(NIHSS) of 4 points or more, catheter related complications, infective complications and thromboembolic complications in addition to all other events fulfilling standard definitions of adverse and serious events will be monitored and documented. The NIHSS will be performed at baseline, 24 hours, 7 days as well as any time a clinical neurological deterioration is suspected. A standard battery of clinical outcome measures will be performed at 90 days - NIHSS, modified rankin scale(mRS), and Barthel Index(BI). Favourable outcomes will be defined as mRS < 3, BI >90, NIHSS < 4.
Timepoint [1] 257118 0
Baseline CT scan and clinical assessment is attended on patients when first admitted to the emergency department. The CT scan is repeated 30 days post stroke to observe the outcome. The participant clinical outcome follow-up measures are attended 90 days post stroke.

Eligibility
Key inclusion criteria
Clinico-radiological assessment consistent with acute hemispheric ischaemic stroke; presentation within 6 hours of the onset of symptoms or within 6 hours of when last seen unaffected; Perfusion cerebral CT scan demonstrating evidence of hypoperfused but still viable hemispheric brain tissue comprising at least 100% of the hypoperfused “region at risk”; National Institutes of Health Stroke Scale (NIHSS) >= 8; Written informed consent from patient, or if appropriate and approval granted, from Person Responsible.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Rapidly improving neurological deficit or deficit that has resolved to NIHSS <8 at time of randomisation; Very severe acute stroke syndrome with Middle Cerebral Artery (MCA) plus Anterior Communicating Artery/Posterior Communicating Artery (ACA/PCA) or any acute MCA syndrome where, at the time of assessment, the site chief investigator considers hemicraniectomy may be required within 36 hours from onset; Any intracranial haemorrhage on baseline imaging; Any known serious co-morbid condition likely to complicate therapy such as a history of cardiac failure requiring pharmacotherapy, chronic liver disease, abdominal or pelvic mass causing femoral or inferior vena caval obstruction, Inferior Vena Cava (IVC) filters; Acute pulmonary oedema, respiratory, renal or hepatic failure as judged by the treating physician; Life expectancy < 3 months due to co-morbid conditions; Pre-morbid modified Rankin scale of >2; Pregnancy (women of child bearing potential will have a urine pregnancy test); Known allergy to pethidine.

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)
We will select acute MCA territory ischaemic stroke patients presenting within 6 hours of onset, with imaging evidence of potentially salvageable brain tissue extending over greater than 100% of the hypoperfused tissue volume. Patients presenting within 3 hours from onset treated with an intravenous thrombolytic medication will be eligible for inclusion in the study. The neurologist obtains informed consent from the patient prior to randomisation. An information statement is given to the patient and the patient is able to read and understand the procedure prior to agreeing to participate. The project is awaiting guardianship approval to obtain person-responsible consent. The patient is aware that they may be randomised to either the hypothermia or normothermia arm of the trial. The on-call stroke nurse or Study Coordinator obtains an opaque gold envelope from a locked cupboard containing CHIL randomisation envelopes in a specified numerical order. The next available envelope is selected and opened in front of an indepenent witness in the emergency department to reveal the treatment allocation. Once randomisation occurs, the patient is informed of the intervention/control treatment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation will be by centre. Randomization will occur at the co-ordinating centre by calling the co-ordinating research nurse who will give the assignment. The sequence will be generated using random number generation (STATA 6.0; Stata Corp. 1999 Statistical Software: Release 5.0 College Station, TX: Stata Corporation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
This research program will involve two parallel international trials. both designed as a “proof of concept” randomised controlled trials. The principle aims of these studies are to examine whether mild hypothermia, administered either by systemic (Australian trial) or local head cooling (Chinese trial) attenuates infarct expansion and salvages penumbral brain tissue using imaging outcome parameters. The safety and tolerability of the interventions will also be assessed. We will select acute MCA territory ischaemic stroke patients presenting within 6 hours of onset, with imaging evidence of potentially salvageable brain tissue extending over greater than 100% of the hypoperfused tissue volume. Patients presenting within 3 hours from onset treated with intravenous tPA will be eligible for inclusion in both countries.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
15/04/2009
Actual
13/05/2009
Date of last participant enrolment
Anticipated
Actual
13/05/2009
Date of last data collection
Anticipated
Actual
Sample size
Target
80
Accrual to date
Final
1
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 1937 0
China
State/province [1] 1937 0
HARBIN

Funding & Sponsors
Funding source category [1] 237467 0
Charities/Societies/Foundations
Name [1] 237467 0
NATIONAL HEART FOUNDATION
Country [1] 237467 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
AUSTRALIAN BRAIN FOUNDATION
Address
P O Box 579, Crows Nest, NSW 1585
Suite 21, Regent House, 37-43 Alexander Street, Crows Nest, NSW 2065
Country
Australia
Secondary sponsor category [1] 236954 0
University
Name [1] 236954 0
University of Newcastle
Address [1] 236954 0
University drive, Callaghan, NSW 2308
Country [1] 236954 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239596 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 239596 0
Lookout Road, New Lambton Heights, NSW 2305
Ethics committee country [1] 239596 0
Australia
Date submitted for ethics approval [1] 239596 0
01/08/2008
Approval date [1] 239596 0
20/08/2008
Ethics approval number [1] 239596 0
08/05/21/3.05

Summary
Brief summary
The CHIL study hypothesis is that not only will systemic or local cooling to 33 degrees C will reduce the size of stroke damage in patients who have sufferred an acute stroke but also that the procedure can be peformed safely.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30020 0
Prof Christopher Levi
Address 30020 0
Hunter Stroke Service
Country 30020 0
Australia
Phone 30020 0
000000000000
Fax 30020 0
Email 30020 0
Chris.Levi@newcastle.edu.au
Contact person for public queries
Name 13267 0
A/Professor Christopher Levi
Address 13267 0
Hunter Stroke Research Group
John Hunter Hospital
Locked Bag 1
Hunter Region mail Centre NSW 2310
Country 13267 0
Australia
Phone 13267 0
+61 2 49 855593
Fax 13267 0
+61 2 49214838
Email 13267 0
christopher.levi@hnehealth. nsw.gov.au
Contact person for scientific queries
Name 4195 0
A/Professor Christopher Levi
Address 4195 0
Hunter Stroke Research Group
John Hunter Hospital
Locked Bag 1
Hunter Region mail Centre NSW 2310
Country 4195 0
Australia
Phone 4195 0
+61 2 49 855593
Fax 4195 0
+61 2 49214838
Email 4195 0
christopher.levi@hnehealth. nsw.gov.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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