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Trial registered on ANZCTR

Registration number

ACTRN12615001159549

Ethics application status

Approved

Date submitted

21/08/2015

Date registered

30/10/2015

Date last updated

30/10/2015

Type of registration

Retrospectively registered

Titles & IDs

Public title

Cerebral Haemodynamics and Orthostatic Response to Upright position in acute ischaemic Stroke (CHORUS)

Scientific title

Cerebral Haemodynamic and Orthosatics Response, in response to Upright Positioning compared to lying flat, for acute ischemic anterior circulation stroke patients with and without occlusion

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

CHORUS

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Anterior circulation Ischemic stroke

Condition category

Condition code

Stroke

Ischaemic

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Upright positioning.
Within 24-48 hours from stroke onset, patients will be moved from a lying flat position to 4 different upright positions with data recorded at each position. The positions will be: head of the bed raised to 30 degrees, head of the bed raised to 70 degrees, 90 degrees sitting (patient sitting unassisted on edge of the bed), and 90 degrees standing. At each position, there is a period of rest (during which no data recorded) followed by 2 minutes of data collection (1 minute of ultrasound recording, followed by approximately 1 minute for collection of other outcomes). The rest period for each position are as follows: one minute after being moved to 30 degrees and 70 degrees, and 10 minutes rest after being moved to 90 degrees sitting. No rest period after being moved to standing position. Degrees will be achieved using a protractor attached to the bed. The protocol will be implemented by 2 researchers.

Intervention code [1]

Treatment: Other

Comparator / control treatment

Lying flat.
The primary comparator will be the lying flat position. All patients will be tested at all positions (as described above), starting with the lying flat position.

Control group

Active

Outcomes

Primary outcome [1]

Change in mean cerebral blood flow velocity between lying flat and sitting at 90 degrees. This will be assessed using bilateral transcranial doppler ultrasound.

Timepoint [1]

Patients are tested within 48 hours of stroke. There will be 10 minutes of rest at the 90 degrees position, followed by 30 seconds of data recording.

Secondary outcome [1]

Safety: proportion of patients with a greater than 50% drop in mean Middle Cerebral Artery velocity relative to baseline (as seen of the Transcranial dopplar ultrasound during testing) or a greater than 2 point increase in scores on the NIHSS items 1, 7, 8 or 13 (conciousness, speech, affected arm). Drops in Middle Cerebral Artery velocity will be monitored on the transcranial doppler ultrasound.

Timepoint [1]

Patients are tested within 48 hours of stroke. Safety outcomes will be monitored during the full protocol (which takes approximately 30 minutes)

Secondary outcome [2]

Difference in the change in mean cerebral blood flow velocity from 0 degrees lying to 90 degrees sitting, between 24-48 hours and 7 days post stroke. Middle Cerebral Artery velocity will be recorded with transcranial doppler ultrasound.

Timepoint [2]

A comparison between data recorded at 24-48 hour and 7 day post stroke

Eligibility

Key inclusion criteria

- 18 years or older
- First or recurrent acute anterior circulation ischaemic stroke
- Recruitment within 48 hours of symptom onset

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

- Cerebral haemorrhage as seen on non-contrast CT
- Milignant middle cerebral artery stroke or posterior circulation ischaemia
- significant premorbid disability (modified rankin score greater than 3)
- unabele o lie flat
- Pregnant
- serious co-morbid illness
- autonomic neuropathy or any concomitant neurodegenerative disorders
- poor acoustic temporal windows

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

Single group

Other design features

Within sample design, all patients tested at all positions

Phase

Not Applicable

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

H1 – We will use a linear regression analysis to examine the difference in response of patients with and without persistent occlusion on moving from 0 degrees to 90 degrees, with change in CBFVmean in the affected hemisphere as an outcome variable, and group and the corresponding change in the contralateral hemisphere as covariants.
H2 – We will use a random effect repeated measures linear regression to examine change in CBFVmean (moving from 0 degrees to 90 degrees) over time. In this analysis change (0-90 degrees) in the affected hemisphere will be an outcome variable, and the time point (24-48hrs vs. 7 days) and the change in the contralateral hemisphere as covariants, with patient as a random effect.
H3 – In this exploratory analysis we will examine the association between CBFVmean and incremental changes in head position (0 degrees, 30 degrees, 70 degrees, 90 degrees, standing) at 24-48 hours post-stroke using a random effects repeated measures analysis with angle as the outcome variable and change in the contralateral hemisphere as a covariant.

Determining sample size: The recent systematic review of TCD in acute stroke found a significant increase in mean flow velocity of 8.3cm/s as patients with vessel occlusion moved from 30 degrees to flat in the affected hemisphere. We aim to detect differences between baseline CBFVmean (0 degrees) and sitting CBFVmean (90 degrees) at 24 hours in patients with vessel occlusion (Primary aim). If we assume that patients without vessel occlusion have no change in CBFV (reasonable based on previous studies), then, to detect a difference in CBFVmean of 8.3 cm/s or greater with a probability of 80 percent (power) when testing at a 2 sided significance level of 5 percent a sample size of 31 patients per group (n=62) is required (H1).
To detect a change in CBFVmean over time (24 hours vs. 3-7 days post-stroke) in patients with persistent vessel occlusion the following assumptions were made. Assuming that the correlation between CBFVmean between 24 hours and 3-7 days is 0.4 or above, using a matched two tailed t-test, a probability of 80 percent (power) and a significance level of 5 percent, a sample size of 68 is required.
In total, therefore, we require 68 patients with persistent vessel occlusion and a further 31 patients without persistent vessel occlusion (n=99).

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

Actual

16/06/2015

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)

VIC

Recruitment hospital [1]

Austin Health - Austin Hospital - Heidelberg

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Address [1]

Country [1]

Primary sponsor type

Other Collaborative groups

Name

Florey Institute of Neuroscience and Mental Health

Address

The Melbourne Brain Center,
245 Burgundy st, Heidelberg, VIC, 3084

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Health Human Research Ethics Committee

Ethics committee address [1]

145 Studley Road
Heidelberg
Victoria
Australia, 3084

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

23/04/2015

Ethics approval number [1]

HREC/15/Austin/34

Summary

Brief summary

Stroke is the leading cause of adult disability and mortality in Australia, with the incidence set to rise as our population ages. The majority of strokes are ischaemic in nature and occur when a blood vessel to the brain is occluded, either by a clot or narrowing of the artery. Cerebral blood flow in acute ischaemic stroke is highly dynamic, and factors that either impair or promote cerebral blood flow during the acute phase may directly affect the infarct size and associated clinical deficit. 

Lowering the head of the bed in the early hours of stroke may theoretically assist flow to the ischaemic tissue, conversely, there is growing support for early mobilisation (getting up) after stroke, with a number of large clinical trials underway.  Currently there is no consensus and no clinical guidelines on the safety of early upright posture when caring for acute stroke patients. We are therefore evaluating the extent and clinical relevance of orthostatic changes in cerebral blood flow in acute ischaemic stroke during position changes using transcranial Doppler ultrasound (TCD). 

The proposed study is a prospective, cohort study of patients with confirmed ischemic (due to a clot) stroke admitted within 24-48 hours of stroke onset to Austin Health. TCD examination is routine for people with stroke at Austin Health. It is performed flat (0 degress) of with the head slightly elevated. In this study, in recruited patients we will extend the current standard care TCD protocol to include measurement of cerebral blood flow velocity in 4 new positions: 30 degrees, 70 degrees, 90 degrees sitting (unsupported) and 90 degrees, standing (if possible). The primary outcome in this study is change in mean cerebral blood flow velocity (CBFVmean) in the middle cerebral artery on the affected stroke hemisphere with change in position from 0 degrees to 90 degrees sitting within the first 24-48 hours of stroke. The assessor of this outcome will be blinded to patient and position.

This study will determine whether changing position to upright at 24-48 hours post stroke influences blood flow velocity in the affected hemisphere and whether this response modifies over the first week after stroke. A better understanding of orthostatic changes in blood flow may have significant clinical impact by providing a physiologic basis to guidelines on early head of bed elevation, positioning, and mobilisation of patients with acute anterior circulation stroke. The information from this study will therefore help inform practice and provide pilot data for a larger study that will aim to more clearly identify best practice protocols in subgroups of patients with different stroke characteristics and risk of impaired cerebral autoregulation.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Julie Bernhardt

Address

The Florey Institute of Neuroscience and Mental Health
The Melbourne Brain Center
245 Burgundy st Heidbelberg
Victoria, 3084

Country

Australia

Phone

+61 3 90357072

Fax

julie.bernhardt@florey.edu.au

Contact person for public queries

Name

Julie Bernhardt

Address

The Florey Institute of Neuroscience and Mental Health
The Melbourne Brain Center
245 Burgundy st Heidbelberg
Victoria, 3084

Country

Australia

Phone

+61 3 90357072

Fax

julie.bernhardt@florey.edu.au

Contact person for scientific queries

Name

Julie Bernhardt

Address

The Florey Institute of Neuroscience and Mental Health
The Melbourne Brain Center
245 Burgundy st Heidbelberg
Victoria, 3084

Country

Australia

Phone

+61 3 90357072

Fax

julie.bernhardt@florey.edu.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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