Clinical trial NCT01812993: Reversal of the Neurological Deficit in Acute Stroke With the Signal of Efficacy Trial of Auto BPAP to Limit Damage From Suspected Sleep Apnea
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Ischemic Stroke
Keywords: Ischemic stroke, sleep apnea, non-invasive ventilatory treatment
Lead sponsor: Technische Universität Dresden
Sponsor class: OTHER
First posted: 2013-03-18
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Early neurological recovery
timeFrame: 72+12 hours from randomization
Secondary outcomes:
measure: Tolerability
timeFrame: During treatment with auto-BPAP; up to 48 hours
measure: Safety
timeFrame: During treatment with auto-BPAP; up to 72 hours from randomization
measure: Signal-of-efficacy
timeFrame: 24 hours; discharge; 90 days from randomization
Other outcomes:
Locations:
city: Memphis
country: United States
facility: University of Tennessee Health Science Center, Department of Neurology
state: Tennessee
city: Linz
country: Austria
facility: Department of Neurology, General Hospital Linz (AKH)
city: Brno
country: Czech Republic
facility: International Clinical Research Center, St. Anne's University Hospital Brno
city: Dresden
country: Germany
facility: Dresden University Stroke Center, University of Technology Dresden,
Study officials:
affiliation: University of Alabama at Birmingham
name: Andrei V. Alexandrov, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Technology Dresden
name: Ulf Bodechtel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Technology Dresden
name: Jessica Kepplinger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Barlinn K, Jakubicek S, Siepmann T, Chernyshev OY, Pallesen LP, Wienecke M, Hermann W, Graehlert X, Alexandrov AW, Vosko M, Puetz V, Reichmann H, Bodechtel U, Mikulik R, Barlinn J, Alexandrov AV. Autotitrating Bilevel Positive Airway Pressure in Large Vessel Steno-Occlusive Stroke Patients With Suspected Sleep Apnea: A Multicenter Randomized Controlled Study. Front Neurol. 2021 Apr 13;12:667494. doi: 10.3389/fneur.2021.667494. eCollection 2021.
citation: Kepplinger J, Barlinn K, Kolieskova S, Shahripour RB, Pallesen LP, Schrempf W, Graehlert X, Schwanebeck U, Sisson A, Zerna C, Puetz V, Reichmann H, Albright KC, Alexandrov AW, Vosko M, Mikulik R, Bodechtel U, Alexandrov AV. 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): study protocol for a randomized controlled trial. Trials. 2013 Aug 13;14:252. doi: 10.1186/1745-6215-14-252.