Acute Ischemic Stroke
Conditions
Keywords
acute ischemic stroke, patient positioning, leg elevation, large artery atherosclerosis, feasibility study
Brief summary
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.
Detailed description
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.
Interventions
OTHERElevated Leg Positioning
Elevated leg positioning (ELP) is a patient positioning strategy initiated no later than 24 hours after stroke onset. Patients are positioned with passive elevation of the legs to 30° while maintaining a 0° head position using calibrated hospital beds. This is maintained for 24 hours, including during eating, drinking, and toileting. After 24 hours, mobilization with toilet privileges may be commenced, and patients are placed in ELP for 3 hours three times daily. Treatment protocol is continued for 7 days. Patients are instructed to report any discomfort while receiving ELP. If deemed uncomfortable or potentially harmful, ELP could be interrupted, during which patients are gradually returned to a horizontal position.
Sponsors
Bonifacio C. Pedreogsa II
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Adhering to the Assigned Elevated Leg Positioning (ELP) Intervention per Protocol | From enrollment to the end of treatment at 7 days. | The primary feasibility outcome was protocol adherence to the assigned elevated leg positioning (ELP) intervention in participants randomized to the intervention arm. Temporary interruption of ELP was permitted for up to three nonconsecutive periods of ≤30 minutes each. Adherence ≥80% prespecified as the threshold for feasibility. |
| Number of Participants With Prespecified Adverse Events During the Treatment Period | From enrollment to the end of treatment at 7 days. | Occurrence of prespecified adverse events during the treatment period. Prespecified adverse events included headache, anxiety or fear, aspiration pneumonia, intracranial hemorrhage, venous thromboembolism (deep vein thrombosis or pulmonary embolism), and other cardiovascular or peripheral vascular events not present at baseline. Serious adverse events were defined according to International Council for Harmonisation Good Clinical Practice criteria and were adjudicated by an independent investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Early Neurologic Deterioration (END) | Within 48 hours after randomization. | Early neurologic deterioration (END), defined as an increase of ≥4 points in the National Institutes of Health Stroke Scale (NIHSS) score within 48 hours not attributable to intracranial hemorrhage. The NIHSS is a clinician-administered scale used to quantify neurologic deficit in stroke, with scores ranging from 0 to 42, where higher scores indicate more severe neurologic impairment. |
| Change from Baseline in the National Institutes of Health Stroke Scale (NIHSS) Score at Day 7 | Baseline and day 7 after randomization. | Change in National Institutes of Health Stroke Scale (NIHSS) score at day 7 compared with baseline. The NIHSS is a clinician-administered scale used to quantify neurologic deficit in stroke, with scores ranging from 0 to 42, where higher scores indicate more severe neurologic impairment. |
| Number of Participants With All-Cause Mortality at 30 Days | 30 days after randomization. | All-cause mortality at 30 days. |
| Number of Participants With Favorable Functional Outcome at 90 Days | 90 days after randomization. | Favorable functional outcome at 90 days, defined as a modified Rankin Scale (mRS) score of 0-2. The mRS is a measure of functional disability ranging from 0 to 6, where 0 indicates no symptoms and 6 indicates death. |
Countries
Philippines
Contacts
STUDY_CHAIRJose C Navarro, MD, MSc
Jose R. Reyes Memorial Medical Center
Outcome results
None listed