Reversal of the Neurological Deficit in Acute Stroke With the Signal of Efficacy Trial of Auto BPAP to Limit Damage From Suspected Sleep Apnea

Study Overview
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Brief Summary
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Although the negative impact of sleep apnea on the clinical course of acute ischemic stroke (AIS) is well known, data regarding non-invasive ventilation in acute patients are scarce. Several studies showed its tolerability, safety and signals-of-efficacy, yet no controlled randomized sequential phase studies currently exist that aim to establish the efficacy of early non-invasive ventilation in AIS patients. The main hypothesis for this study is that early non-invasive ventilation with automated bilevel positive airway pressure (auto-BPAP) positively affects short-term clinical outcomes in AIS patients. This is a multicenter, prospective, randomized, controlled, third rater-blinded, parallel-group trial. Patients with AIS with proximal arterial obstruction and clinically suspected sleep apnea will be randomized to standard or standard stroke care plus auto-BPAP. Auto-BPAP will be initiated within 24 hours from stroke onset and performed for a maximum of 48 hours during diurnal and nocturnal sleep. Patients will undergo cardiorespiratory polygraphy between day 3 and 5 to assess sleep apnea. The primary endpoint is any early neurological improvement on the NIHSS at 72 hours from randomization. Safety, tolerability, short-term and 3 months functional outcomes are assessed as secondary endpoints by un-blinded and blinded observers respectively. This study will provide data to power a subsequent phase III study.

Official Title
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Reversal of the Neurological Deficit in Acute Stroke With the Signal of Efficacy Trial of Auto BPAP to Limit Damage From Suspected Sleep Apnea (Reverse-STEAL): A Multicenter Randomized Study

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Device: Non-invasive ventilatory treatment with auto-BPAP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients 18 - 80 years; Clinical suspicion of an AIS (measurable or fluctuating neurological deficit with a National Institutes of Health Stroke Scale [NIHSS] ≥ 4 points) within 24 hours from symptom-onset; Extracranial (internal carotid artery) or intracranial (internal carotid artery; middle/anterior/posterior cerebral arteries) ≥ 50% stenosis, near-occlusion or occlusion diagnosed by ultrasound, computed tomography angiography (CTA) or magnetic resonance angiography (MRA), corresponding to acute neurological deficit; High-risk of having sleep apnea (classified by the Berlin sleep apnea questionnaire); or history of known sleep apnea; or witnessed repetitive apnea episodes during sleep or somnolence during hospitalization; Written informed consent by participants; alternatively by proxy or two physicians when not obtainable by patient or proxy (according to local regulations). Exclusion Criteria: Perceived course towards the malignant middle cerebral artery infarction; Immediate or perceived need for intubation; Known sleep apnea currently on non-invasive ventilatory treatment; Standard contraindications for non-invasive ventilatory treatment; Pre-morbid modified Rankin scale (mRS) score ≥ 3; Severe comorbidities (i.e., severe heart failure, severe obstructive lung disease, active malignant disease, severe dementia); Pregnant and breast feeding women; Participation in another clinical trial other than standard-of-care registry.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>No ventilatory treatment; standard stroke care | |
| Experimental: Active<br>Non-invasive ventilatory treatment with auto-BPAP plus standard stroke care | Device: Non-invasive ventilatory treatment with auto-BPAP<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early neurological recovery | Early neurological recovery will be assessed as any improvement on the NIHSS score at 72+12 hours from randomization | 72+12 hours from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability | Tolerability will be assessed by patients' adherence to auto-BPAP (defined as tolerating the treatment during sleep or somnolence for at least 4 hours continuously) | During treatment with auto-BPAP; up to 48 hours | 
| Safety | Safety will be assessed by: (i) frequency of serious adverse events (i.e., aspiration, aspiration pneumonia defined as combined radiologic, white blood count and clinical findings, respiratory failure with/without intubation) during treatment period that in the opinion of the study physician are causatively and timely (for a maximum of 72 hours from treatment initiation) related to auto-BPAP and all deaths during hospital stay. For comparison, patients in the control group will be monitored for respiratory complications within 72 hours from randomization; (ii) frequency of all complaints and possible side effects of auto-BPAP (i.e., local irritation of skin/mucosa, mucosal dryness, nausea/vomiting); (iii) any concerns by hospital nursing staff will be documented as adverse events since patients will be under standard of care repeated assessments set by admission protocols and treating physicians. | During treatment with auto-BPAP; up to 72 hours from randomization | 
| Signal-of-efficacy | Signal-of-efficacy: Clinical and functional outcomes will be assessed by: (i) frequency of neurological deterioration (increase in baseline NIHSS score ≥4 points) at 24, 48 and after 72 hours from randomization by blinded observers; (ii) frequency of early neurological improvement (decrease in baseline NIHSS score ≥4 points) at 24, 48 and after 72 hours from randomization by blinded observers; (iii) good functional outcome (mRS score 0-2) at discharge and at 3 months by blinded observers; (iv) any TIA or new ischemic stroke during hospitalization or within 3 months of protocol initiation. | 24 hours; discharge; 90 days from randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ischemic stroke, sleep apnea, non-invasive ventilatory treatment