Augmentation of penumbral perfusion through nonpharmacological hemodynamic interventions such as patient positioning may offer a pragmatic approach to improve outcomes in acute ischemic stroke (AIS). This study aimed to assess the feasibility and safety of elevated leg positioning (ELP) in AIS, and to generate preliminary estimates of effect sizes to inform the design of a future definitive randomized trial.

The acute phase of ischemic stroke is a potentially reversible process wherein the extent of tissue injury is dependent on the severity and duration of the perfusion deficit, which are strongly influenced by the adequacy of collateral circulation and the timing of arterial blood flow restoration relative to the window of cellular viability. In addition to pharmacologic and mechanical reperfusion therapies, measures that augment perfusion to the salvageable ischemic penumbra may mitigate subsequent infarct progression and associated neurological deficits.

Accordingly, patient positioning strategies intended to enhance cerebral perfusion and oxygenation during the early management of acute ischemic stroke (AIS) may offer a simple and cost-effective nonpharmacologic approach to improve outcomes. Two strategies, the 0° and lower head (-20° Trendelenburg) positions, have been evaluated in randomized clinical trials but have yielded inconclusive findings.

This study proposes elevated leg positioning (ELP) while maintaining a 0° head position as a physiologically plausible hemodynamic intervention to optimize penumbral perfusion. In theory, this position would increase venous return and preload, thereby augmenting cardiac output while simultaneously minimizing the hydrostatic pressure gradient between the heart and brain, resulting in increased cerebral perfusion pressure and improved collateral circulation. This may be particularly relevant in the setting of an acute ischemic insult, where focal impairment of cerebrovascular autoregulation may render cerebral blood flow to the penumbra increasingly pressure-passive and dependent on systemic hemodynamics. Furthermore, compared with lower head positioning strategies, maintenance of a neutral head and airway position may confer safety and tolerability advantages.

The present study was designed to assess the feasibility and safety of ELP initiated within 24 hours of symptom onset or last known well in patients with moderate anterior circulation ischemic stroke with probable large artery atherosclerosis (LAA) etiology, and to generate preliminary estimates of effect sizes to inform the design and sample size calculation of a future definitive randomized trial.

Inclusion Criteria:

• Age ≥18 years.
• Acute ischemic stroke (AIS) confirmed by cranial computed tomography (CT) or magnetic resonance (MR) imaging.
• Time from onset (symptom onset or last known well) to enrollment of ≤24 hours.
• Moderate neurological deficit (National Institutes of Health Stroke Scale [NIHSS] score of 6-16).
• Probable large artery atherosclerosis (LAA )etiology based on the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria (confirmed by cranial CT or MR angiography and carotid duplex ultrasonography performed on admission).
• Evidence of unilateral stenosis or occlusion of the internal carotid artery (ICA) or the M1 or proximal M2 segment of the middle cerebral artery (MCA) corresponding to the presumed culprit artery.
• Functional independence prior to stroke (modified Rankin Scale [mRS] score ≤1).
• Written informed consent signed by the patient or their legally authorized representative.

Exclusion Criteria:

• Decreased level of consciousness (NIHSS item 1a ≥1).
• Planned or completed intravenous thrombolysis and/or endovascular therapy.
• Planned carotid or intracranial revascularization within 3 months.
• Evidence of intracranial hemorrhage on neuroimaging.
• Alternative stroke etiologies (e.g., cardioembolism, non-atherosclerotic arteriopathies).
• Serious systemic illness (e.g., significant hepatic or renal insufficiency, active malignancy).
• Prior stroke with significant residual neurological deficit (mRS ≥2).
• History of intracerebral hemorrhage within the preceding 12 months.
• Any possible contraindication to ELP (e.g., active vomiting, pneumonia, uncontrolled heart failure).
• Participation in another clinical trial within the preceding 3 months.
• Pregnancy or lactation.
• Any other condition deemed inappropriate for participation by the investigators.

All de-identified IPD that underlie results in a publication.

Beginning within 1 year after study completion (on or before December 31, 2026) and available indefinitely.

Deidentified IPD and supporting information will be made publicly available and deposited in a publicly accessible data repository without restriction.