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

Phase 2

• Conditions: Ischemic Stroke
• Interventions: Device: Non-invasive ventilatory treatment with auto-BPAP

• Registration Number: NCT01812993
• Lead Sponsor: Technische Universität Dresden

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-03
• Study First Submitted: 2013-03-14
• Study First Submitted QC: 2013-03-14
• Study First Posted: 2013-03-18
• Status Verified: 2015-02
• Last Update Submitted: 2015-02-10
• Last Update Posted: 2015-02-12
• Primary Completion: 2015-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active	Non-invasive ventilatory treatment with auto-BPAP	Non-invasive ventilatory treatment with auto-BPAP plus standard stroke care

Primary Outcome Measures

Name	Time	Method
Early neurological recovery	72+12 hours from randomization	Early neurological recovery will be assessed as any improvement on the NIHSS score at 72+12 hours from randomization

Secondary Outcome Measures

Name	Time	Method
Safety	During treatment with auto-BPAP; up to 72 hours from randomization	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.
Signal-of-efficacy	24 hours; discharge; 90 days from randomization	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.
Tolerability	During treatment with auto-BPAP; up to 48 hours	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)

Trial Locations

Locations (4)

University of Tennessee Health Science Center, Department of Neurology; 🇺🇸 Memphis, Tennessee, United States

Department of Neurology, General Hospital Linz (AKH); 🇦🇹 Linz, Austria

Dresden University Stroke Center, University of Technology Dresden,; 🇩🇪 Dresden, Germany

International Clinical Research Center, St. Anne's University Hospital Brno; 🇨🇿 Brno, Czech Republic