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

Ischemic Stroke Clinical Trial

— Reverse-STEAL  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01812993
• Other study ID #: RES03_2013
• Status: Recruiting
• Phase: Phase 2
• First received: March 14, 2013
• Last updated: February 10, 2015
• Start date: March 2013

Study information

• Verified date: February 2015
• Source: Technische Universität Dresden
• Contact: Jessica Kepplinger, MD
• Phone: +49-351-458-18515
• Email: jessica.kepplinger[@]uniklinikum-dresden.de
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ischemic Stroke
• Stroke

Intervention

Device:
• Non-invasive ventilatory treatment with auto-BPAP

Locations

Country	Name	City	State
Austria	Department of Neurology, General Hospital Linz (AKH)	Linz
Czech Republic	International Clinical Research Center, St. Anne's University Hospital Brno	Brno
Germany	Dresden University Stroke Center, University of Technology Dresden,	Dresden
United States	University of Tennessee Health Science Center, Department of Neurology	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Technische Universität Dresden

Countries where clinical trial is conducted

United States,  Austria,  Czech Republic,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	No