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Trial registered on ANZCTR


Registration number
ACTRN12618000698279
Ethics application status
Approved
Date submitted
17/04/2018
Date registered
30/04/2018
Date last updated
30/04/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Head positioning for Stroke blood flow Augmentation assisting Reperfusion Therapies
Scientific title
Assessment of head positioning below horizontal in patients with acute ischaemic stroke suitable for reperfusion therapies: CT perfusion lesion volume changes and clinical correlates.
Secondary ID [1] 294613 0
none
Universal Trial Number (UTN)
Trial acronym
HEAD-START
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Ischaemic Stroke 307446 0
Condition category
Condition code
Stroke 306533 306533 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A standard of care CT perfusion scan is performed in all patients, followed by an additional CT perfusion scan (with torso and limbs on a 20 degree angled foam wedge) if a perfusion lesion of >30ML is identified and the patient or proxy consents. Patients who are identified as CT perfusion 'responders' to head positioning (based on the improvement of TMAX>6 (or delay time >3) lesion volume reduction of greater than or equal to 5Ml following repeat CT perfusion ) will be placed in the 15 degree head down position on a regular hospital barouche for 24 hours, or whenever TICI IIC/III reperfusion is achieved. Non-responders will received normal standard of care positioning. Blood pressure is recorded during both the supine and 'heads down' CT scans. All patients will have an NIHSS score and blood pressure measurement performed by authorised blinded trial staff following 5 minutes of 'heads down' and then 'heads up' position immediately following the scan. The patient is then assigned to 24 hours of positioning based on the CT perfusion findings. The responsibility of maintaining and recording head positioning lies with the stroke specialist nurse who is looking after the patient for the first 24 hours. Post 24 hour NIHSS, 24 hour MRI/A (+/- perfusion) and 90day follow-up is assessed by stroke unit staff and is standard of care.
Intervention code [1] 300920 0
Treatment: Other
Comparator / control treatment
The comparator will be historical matched controls for reperfusion and ischaemic volume, with the primary measure of outcome being expected volume of infarcted tissue at 24 hours MRI or CT. For the purposes of determining whether the patient is a 'responder' to CT perfusion, the patient will serve as their own internal control.
Control group
Historical

Outcomes
Primary outcome [1] 305539 0
Mean change in TMAX>6s (or delay time >3s) ischaemic lesion volume following 5 minutes of 20 degree heads down positioning
Timepoint [1] 305539 0
The immediately acute 2nd CT perfusion scan
Secondary outcome [1] 345665 0
1) To demonstrate (in ‘responders’) whether altered body position acutely affects neurologic function. Measured by change in NIHSS following positional change
Timepoint [1] 345665 0
Immediately following the CT scan following 5 minutes of head positioning
Secondary outcome [2] 345666 0
Observed versus expected progression of penumbral tissue to infarction measured by 24 hour MRI.
Timepoint [2] 345666 0
24 hours post-baseline imaging.
Secondary outcome [3] 345667 0
Modified Rankin score (assessing stroke-related disability)
Timepoint [3] 345667 0
90 days post-stroke
Secondary outcome [4] 345668 0
Time spent in hospital
Timepoint [4] 345668 0
90 days post-stroke
Secondary outcome [5] 345763 0
Time spent at home
Timepoint [5] 345763 0
90 days post-stroke
Secondary outcome [6] 345764 0
EuroQol - 5D
Timepoint [6] 345764 0
90 days post-stroke
Secondary outcome [7] 345766 0
Safety outcome - Number of patients with aspiration pneumonia - Assessed by review of medical records
Timepoint [7] 345766 0
48 hours post-baseline CT scan
Secondary outcome [8] 345767 0
Safety outcome - Serum creatinine (standard of care)
Timepoint [8] 345767 0
48 hours post-baseline CT scan
Secondary outcome [9] 345768 0
Tolerability outcome - time spent in proscribed position
Assessed hourly by stroke specialist nurse and recorded on proforma
Timepoint [9] 345768 0
hourly for the first 24 hours
Secondary outcome [10] 345769 0
Tolerability outcome - visual analogue score 1-10 ('how uncomfortable are you' subjective score 1-10, scored by observer if patient cannot comprehend)
Timepoint [10] 345769 0
At hours 1,3,6 12 and 24 in the first 24 hours post-baseline CT scan
Secondary outcome [11] 345770 0
Clinically significant left ventricular failure - left ventricular failure as recorded in the medical record, requiring either medical treatment or cessation of 'heads down' positioning
Timepoint [11] 345770 0
24 hours post-stroke
Secondary outcome [12] 346138 0
Neurological function as measured by NIHSS
Timepoint [12] 346138 0
Day 3 post-CT or discharge from the acute hospital, whichever is earliest

Eligibility
Key inclusion criteria
1) Acute anterior circulation ischaemic stroke with measurable neurologic deficit
2) Demonstration of penumbra of CT perfusion imaging (TMax lesion (>6 seconds) volume > 30 mL, as measured by RAPID software)
Minimum age
60 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Known renal failure (eGFR < 30mL)
2) Posterior circulation stroke with dysphagia
3) Clinically evident or recent (<1 month) left ventricular failure
4) Iodine contrast hypersensitivity
5) Any other contraindication to ‘head down’ position (evident increased respiratory effort, nausea and vomiting)
6) <60 years old
7) High probability of death within the next 48 h
8) Planned early decompressive craniectomy

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Other
Other design features
Patients undergo standard of care CT perfusion for suspected ischaemic stroke. If a TMax lesion of >30ml is identified and consent has been obtained, blood pressure is repeated, the patient is placed on a 20 degree foam wedge, blood pressure is repeated and the CTP is repeated. Following this procedure the patient is removed from the CT scanner, place in the 15 degrees head down position and a NIHSS and BP is performed. This is then repeated following 5 minutes of 30 degree heads up positioning. These assessment are performed blinded to CTP results. If the patients is a responder on CTP (defined as a greater than 5Ml reduction in the TXAX>6 s lesion) they are placed in the 15 degree head down position until 24 hours, or whenever reperfusion (TICI IIC/III) is achieved. Non-responders are placed in the traditional 30 degree heads up position. Hourly documentation of vital signs and head position is performed. 24 hour MRI/MRA is performed (or CT/CTA). This scan may include perfusion imaging if subsequent funding is obtained. Analysis of CTP perfusion data will be performed for the final analysis in pairs to ensure matching of AIF and VOF selection, but blinded to positioning.
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Primary outcome is assessed by a paired T-test. Change in NIHSS following head positioning in responders and non-responders will be assessed with the Friedman test.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 10691 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 22413 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 299228 0
Hospital
Name [1] 299228 0
Royal Adelaide Hospital
Address [1] 299228 0
1 Port Road Adelaide SA 5000
Country [1] 299228 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
1 Port Road Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 298500 0
None
Name [1] 298500 0
Address [1] 298500 0
Country [1] 298500 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300153 0
CALHN Research Ethics
Ethics committee address [1] 300153 0
Royal Adelaide Hospital 1 Port Road Adelaide SA 5000
Ethics committee country [1] 300153 0
Date submitted for ethics approval [1] 300153 0
24/04/2017
Approval date [1] 300153 0
17/08/2017
Ethics approval number [1] 300153 0
HREC/17/RAH/164

Summary
Brief summary
The purpose of the study is to evaluate the effects of head-down positioning (15 degrees below horizontal) in acute stroke, using both clinical and radiographic outcome measures.

Primary Aim:
1) To demonstrate definitively whether body positioning improves cerebral blood flow in acute ischaemic stroke, as measured by CT perfusion imaging

Secondary Aims:
1) To demonstrate (in ‘responders’) whether altered body position acutely affects neurologic function
2) To determine (in ‘responders’) whether altered body positioning (15 degrees head down) lessens the likelihood of progression of ‘penumbra’ to infarction, as assessed by 24 hour magnetic resonance imaging.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82718 0
A/Prof Timothy Kleinig
Address 82718 0
Department of Neurology Royal Adelaide Hospital 1 Port Road Adelaide SA 5000
Country 82718 0
Australia
Phone 82718 0
+61 421 832 272
Fax 82718 0
Email 82718 0
timothy.kleinig@sa.gov.au
Contact person for public queries
Name 82719 0
A/Prof Timothy Kleinig
Address 82719 0
Department of Neurology Royal Adelaide Hospital 1 Port Road Adelaide SA 5000
Country 82719 0
Australia
Phone 82719 0
+61 421 832 272
Fax 82719 0
Email 82719 0
timothy.kleinig@sa.gov.au
Contact person for scientific queries
Name 82720 0
A/Prof Timothy Kleinig
Address 82720 0
Department of Neurology Royal Adelaide Hospital 1 Port Road Adelaide SA 5000
Country 82720 0
Australia
Phone 82720 0
+61 421 832 272
Fax 82720 0
Email 82720 0
timothy.kleinig@sa.gov.au

No data has been provided for results reporting
Summary results
Not applicable