Primary aim is to compare the effects of lying flat (0°) head position with sitting up (≥30°)
head position applied in the first 24 hours of admission, for patients presenting with acute
ischemic stroke (AIS), on the poor outcome of death or disability at 90 days.
Key secondary aim is to determine whether lying flat is superior to sitting up on poor
outcome (death and neurological impairment) at 7 days in AIS; and whether sitting up is
superior to lying flat on these outcomes in acute intracerebral hemorrhage (ICH).
The hospitals will be required to undertake recruitment of 70 consecutive acute stroke
patients of all stroke types, with the power calculations undertaken on a target of 50 AIS
patients per site. In the use of consecutive patient recruitment, it is anticipated that an
average of 10 ICH patients will also be included within the 70 target patients, before
crossing over to the other interventional phase for another 70 target patients recruited. The
hospitals will have training, prior to their activation and commencement of the intervention.
Data collection at baseline, first 24 hours, discharge/ Day 7, and Day 90 (end of follow-up),
will be captured through a web database. Randomised allocation of intervention will be
assigned by a statistician not otherwise involved in the study according to a statistical
program stratified by the country of the site.
A mixed consent process is proposed, according to local/national rules and regulations, for
the following protocol:
Cluster Guardian consent or appropriate approval (e.g. signed by General Manager or
Chief Executive of hospital, or Head of Neurology/Stroke Department) for the randomised
head position to be the new usual nursing care for patients with acute stroke;
With one of the following:
i. Individual standard consent for the collection of data through in-person assessment and
data extraction from medical records during the hospital stay and follow-up, and for release
of personalised information for research purposes to allow centralised follow-up at 90 days
after admission, or ii. Opt-out consent for collection of data through in-person assessment
and data extraction from medical records during the hospital stay and follow-up, and for
release of personalised information for research purposes to allow centralised follow-up at
90 days after admission.
All acute stroke patients should be managed by a dedicated stroke team or in an acute stroke
unit (or high dependency unit or intensive care unit) during the period of the intervention.
During the intervention and follow-up periods, management of acute stroke patients should be
followed according to published guidelines. It is anticipated that background care may
include use of specific treatments including drugs, intravascular reperfusion therapies and
surgical evacuation. As part of standard stroke care, swallowing function will be evaluated
using local standard procedures before initiation of feeding.
The internet based data management system is managed at the George Institute for Global
Health, which has extensive experience in clinical trial data capture and security. The
George Institute has in place system security SOP with VeriSign SSL digital certification and
encrypted HTTPS connection. Only staff listed in the delegation log will be given unique
individual password to access the internet-based data management system.
Paper CRFs will be provided for sites preferring to use these for the initial collection of
data. These forms will be used as source document and will need to be signed and dated by the
investigator completing the form.
All computerised forms will be electronically signed (by use of the unique password) by the
authorised study staff and all changes made following the initial entry will have an
electronic dated audit trail. It is the requirement that the collection of data and transfer
of information for the 90 day follow-up assessment has to be approved by the local IRB for
each site.
The power of the study is derived from having a very large number of clusters, which will be
achievable as the workload at each centre will be kept low. The inflation of the cluster size
and the number of clusters is to take into account, stroke mimics, and poor recruitment
and/or quality issues in some sites. The target of 70 patients in each intervention is
derived from 10 patients in the initial learning phase, 50 AIS and 10 ICH. For the smaller
Stroke Units that admits 200 strokes per annum, this will likely be achieved over 4-5 months,
so including the crossover and 3 months follow-up the total duration of study is ~12 months.
However, for a large stroke unit, such as in many of the hospitals in China, where 1200 cases
of stroke are admitted per annum, the required 70 patients will be recruited over ~3 weeks,
for a study duration of 4-5 month. Thus, the overall target number of stroke patients to be
recruited at each centre is 140 (i.e. 2 x 70), which will take from 1 to 10 months
considering crossover and according to size (i.e. stroke case load) of the hospital and a
study duration of 4 to 12 months per site considering follow-up. All analyses will be
undertaken at the patient level on an intention-to-treat basis defined by allocated head
position at each centre using Generalised Estimating Equations (GEE) or random-effects
regression to account for clustering.
Publication of the main reports from the study will be in the name of the HeadPoST
Collaborative Investigators. Full editorial control will reside with a Writing Committee
approved by the Steering Committee (SC).
Central international coordination is from GI, Sydney and together with RCCs established and
located in Beijing China, Preston UK, Paris France and Santiago Chile, the study will be
overseen by an International SC comprised of world experts in the fields of stroke,
neurocritical care, neurology, geriatrics, cardiovascular epidemiology and clinical trials.
The ICC will also be supported by key grant holders and regional experts in the Operations
Committee (OC). The PIs of the 140 participating hospitals (see study organisational chart)
will be administratively tied through a structure designed to enhance effective
communication, collaboration and study monitoring by maintaining operations through adherence
to a common protocol.
Data Safety & Monitoring Board (DSMB): The DSMB will review the safety, ethics and outcomes
of the study.
The DSMB will be governed by a charter that will outline their responsibilities, procedures
and confidentiality. Members of the DSMB include: Professor Robert Herbert, (Chair),
Neuroscience Research Australia, University of New South Wales, Sydney Australia; Associate
Professor Christopher Chen, National University of Singapore, Singapore; Professor Anne
Forster, Bradford Institute for Health Research, Bradford, UK A DSMB will also review
unblinded data from the study at regular intervals during follow-up, and will monitor
neurological and functional changes (between the two groups), drop-out and event rates. The
first meeting will be held 3 months after the start of the study. One or two formal interim
analysis will be planned to review data relating to treatment efficacy, patient safety and
quality of trial conduct.
