Ischemic StrokePhase 2Reverse-STEALNCT01812993
Reversal of the Neurological Deficit in Acute Stroke With the Signal of Efficacy Trial of Auto BPAP to Limit Damage From Suspected Sleep Apnea
A Phase 2 study testing Non-invasive ventilatory treatment with auto-BPAP in people with Ischemic Stroke, run by Technische Universität Dresden at 4 sites in 4 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- Non-invasive ventilatory treatment with auto-BPAP
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 4 sitesin 4 countries
- Study dates
- Mar 2013to Dec 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
United States1 site, 1 recruiting
- Not yet recruiting
University of Tennessee Health Science Center, Department of Neurology
Memphis, Tennessee, 38163
Andrei V. Alexandrov, MD
Andrei Alexandrov, MD
Austria1 site, 1 recruiting
- Recruiting
Department of Neurology, General Hospital Linz (AKH)
Linz
Milan Vosko, MD
Czechia1 site, 1 recruiting
- Recruiting
International Clinical Research Center, St. Anne's University Hospital Brno
Brno
Robert Mikulik, MD
Robert Mikulik, MD
Germany1 site, 1 recruiting
- Recruiting
Dresden University Stroke Center, University of Technology Dresden,
Dresden
Jessica Kepplinger, MD, +49-351-458-18515
Jessica Kepplinger, MD
About this study
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
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.
- Conditions
- Ischemic Stroke
- Being tested
- Non-invasive ventilatory treatment with auto-BPAP
- Keywords
- Ischemic stroke, sleep apnea, non-invasive ventilatory treatment
- Medical subject headings
- Ischemic Stroke, Sleep Apnea Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non-invasive ventilatory treatment with auto-BPAPDevice
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | No ventilatory treatment; standard stroke care |
| Active | Experimental | Non-invasive ventilatory treatment with auto-BPAP plus standard stroke care Receives: Device: Non-invasive ventilatory treatment with auto-BPAP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early neurological recovery
Early neurological recovery will be assessed as any improvement on the NIHSS score at 72+12 hours from randomization
Measured: 72+12 hours from randomization
Secondary outcomes (3)
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)
Measured: 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.
Measured: 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.
Measured: 24 hours; discharge; 90 days from randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2013 (estimated)
- Study startMar 2013
- Primary completionDec 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- More trials run by Technische Universität DresdenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Technische Universität Dresden
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Jessica Kepplinger, Technische Universität Dresden
- Investigators
- Andrei V. Alexandrov, MD, Principal investigator, University of Alabama at BirminghamUlf Bodechtel, MD, Principal investigator, University of Technology DresdenJessica Kepplinger, MD, Principal investigator, University of Technology Dresden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01812993
- Sponsor's protocol ID
- RES03_2013
- Acronym
- Reverse-STEAL
- Status last verified
- Feb 2015
- First submitted
- 14 Mar 2013
- Last updated
- 12 Feb 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 33927689Kepplinger 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.
PubMed 23941576
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01812993
- Acronym / sponsor ID
- Reverse-STEAL / RES03_2013
- Conditions
- Ischemic Stroke
- Keywords
- Ischemic stroke, sleep apnea, non-invasive ventilatory treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Technische Universität DresdenUniversity, hospital or other
- Study start
- Mar 2013
- Primary completion
- Dec 2015 (estimated)
- First posted
- 18 Mar 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –No ventilatory treatment; standard stroke care |
| Active | Experimental | Device: Non-invasive ventilatory treatment with auto-BPAPNon-invasive ventilatory treatment with auto-BPAP plus standard stroke care |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Non-invasive ventilatory treatment with auto-BPAP | Device | Active |
Primary outcome
Early neurological recovery
Time frame: 72+12 hours from randomization
Early neurological recovery will be assessed as any improvement on the NIHSS score at 72+12 hours from randomization
3 secondary outcomes
Tolerability
Time frame: During treatment with auto-BPAP; up to 48 hours
Safety
Time frame: During treatment with auto-BPAP; up to 72 hours from randomization
Signal-of-efficacy
Time frame: 24 hours; discharge; 90 days from randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2015.
- Derived from this study: PubMed 33927689Barlinn 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.
- Derived from this study: PubMed 23941576Kepplinger 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrei V. Alexandrov, MD principal investigator
University of Alabama at Birmingham
Ulf Bodechtel, MD principal investigator
University of Technology Dresden
Jessica Kepplinger, MD principal investigator
University of Technology Dresden
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Non-invasive ventilatory treatment with auto-BPAP in people with Ischemic Stroke, run by Technische Universität Dresden at 4 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Austria, Czechia, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jessica Kepplinger, MD (+49-351-458-18515, jessica.kepplinger@uniklinikum-dresden.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Early neurological recovery (time frame: 72+12 hours from randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01812993, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2015.