Early Sleep Apnea Treatment in Stroke

NCT02554487 | Unknown

• 5 other identifiers: 016/152734320030_149752SNCTP00000152133IC30_166827
• Study Type: interventional
• Target: 201
• Locations: 4 countries
• Sites: 6

Brief Summary

Investigating the interrelation of stroke and sleep-disordered breathing (SDB) is of major importance. First because of the high occurrence rate of stroke and the fact that it is a frequent cause of long-term disability in adulthood. Second because SDB (obstructive, central and mixed forms) affects more than 50% of stroke survivors and has a detrimental effect on clinical stroke outcome. Third, spontaneous and learning-dependent sleep-associated neuroplasticity may be affected by SDB following stroke worsening stroke rehabilitation. Therefore, it is crucial to investigate whether early treatment of SDB with Adaptive Servo-Ventilation (ASV), the treatment device of choice to treat obstructive, central and mixed forms of SDB, has a beneficial effect on the evolution of the lesion volume and on clinical stroke outcome. To this end, the investigators recruit and prospectively follow 3 groups of patients with ischemic stroke over 1 year. During the first night after hospital admission due to acute stroke, nocturnal breathing is assessed by means of a respiratory polygraphy. Patients with significant sleep disordered breathing, defined as an Apnea-Hypopnea-Index (AHI) \> 20/h, are randomized to ASV treatment or no treatment (sSDB ASV+ or sSDB ASV-). ASV treatment starts the second night following hospital admission and ends 90 days later. Stroke patients without SDB (AHI \< 5 / h) serve as a control group (no SDB) to observe the evolution of the lesion volume and stroke outcome without the additional burden of SDB. Lesion volume one day after hospital admission due to acute stroke (after potential lysis therapy) measured by Diffusion Weighted Imaging will be subtracted from lesion volume measured by T2-weighted volumetry assessed 90(+/-7) days following stroke and compared between patients with and without ASV treatment (sSDB ASV+ and sSDB ASV-) as well as patients without SDB (no SDB). Short- and long-term clinical stroke outcomes are assessed by clinical scales and questionnaires 4 to 7 days, 3 months and 1 year following stroke. Cognitive outcome is assessed during hospitalization (within the first week following stroke) and after the treatment period of 90 days by neuropsychological tests assessing attention and memory. In addition, baseline assessment of physiological parameters such as blood pressure and endothelial function/arterial stiffness are assessed during the first weeks following stroke and at the end of the treatment period, i.e. approximately 90 days following stroke.

Conditions

Sleep Apnea, Obstructive; Sleep Apnea, Central; Stroke

Keywords

stroke; sleep disordered breathing; sleep apnea; infarct volume; penumbra

Outcome Measures

Primary Outcomes (1)

• Infarct growth from baseline to 90 day following stroke: difference in lesion volume [ccm] assessed by Diffusion Weighted Imaging (DWI) at baseline and T2-weighted imaging at day 90 following stroke

  The day after admission and potential lysis therapy, at 4 to 7 days following stroke and 90 (+/-7 ) days following stroke

Secondary Outcomes (6)

• Relative salvage of the penumbra volume from the day after lysis therapy to day 4-7 following stroke will be compared between the three patients groups (sSDB ASV+, sSDB ASV-, no SDB)

  The day after admission/potential lysis therapy and at 4 to 7 days following stroke

• Differences in spatial/temporal dynamics of resting state connectivity between the three patients groups: sSDB ASV+, sSDB ASV-, no SDB

  The day after admission/potential lysis therapy, at day 4-7 and day 90 following stroke

• Differences in clinical outcome between the three patients groups, sSDB ASV+, sSDB ASV- and no SDB, assessed by the NIHSS, Barthel Index and the modified Rankin scale

  Pre-stroke assessment during hospitalization and post-stroke assessments at day 90 and 1 year following stroke

• Differences in blood pressure measurements (absolute values and variability) during hospitalisation, during a 3-week period following dismissal and during a 3-week period 90-days following stroke.

  3 weeks following hospital discharge (baseline) and 3-weeks before end of intervention period (~day 69-90).

• Differences in endothelial functioning/arterial stiffness at day 2 (baseline) and at 90 days following stroke

  3 weeks following hospital discharge (baseline) and 3-weeks before end of intervention period (~day 69-90).

Study Arms (3)

sSDB ASV+

EXPERIMENTAL

sSDB ASV+: Patients with an AHI \> 20/h assessed during the first night of stroke that are randomized to ASV treatment (AirCurveTM10 CS PACEWAVE Adaptive-Servo-Ventilator (ResMed Ldt., Australia)).

Device: AirCurveTM10 CS PACEWAVE Adaptive-Servo-Ventilator (ResMed Ldt., Australia)

sSDB ASV-

NO INTERVENTION

sSDB ASV-: Patients with an AHI \> 20 no ASV treatment.

no SDB

NO INTERVENTION

no SDB: Stroke patients without SDB (AHI \< 5 / h) serve as a control group to observe the evolution of the lesion volume and stroke outcome without the additional burden of SDB.

Interventions

AirCurveTM10 CS PACEWAVE Adaptive-Servo-Ventilator (ResMed Ldt., Australia) DEVICE

Adaptive Servo-Ventilation (ASV) is a ventilator mode used to treat central and obstructive forms of sleep disordered breathing. It is authorized in Switzerland, bears a conformity marking (CE 0123) and it is used according to the approved indications. Stroke patients with an AHI \> 20/h assessed within the first night following stroke that are randomized to ASV treatment, starting in the second night after stroke, are part of this group. The other half of patients are randomized to no treatment and patients without sleep disordered breathing (AHI \< 5) following stroke serve as a control group

sSDB ASV+

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent as documented by signature
• Admission to one of the participating centers
• Age 18-85 years
• Ischemic stroke detectable by neuroimaging, affecting internal carotid artery, anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA) and/or branches thereof
• Symptom onset to admission \< 24 hours
• AHI \> 20/h or \< 5/h

You may not qualify if:

• Primary hemorrhagic stroke
• Secondary parenchymal haemorrhage (PH 1 and PH 2 according to ECASS; secondary haemorrhagic infarction HI 1 and HI 2 can be included)
• Small strokes (diameter \< 1.5cm)
• Coma/Stupor
• Intubation
• Clinically unstable or life threatening condition (oxygen-dependent pulmonary disease or severe pulmonary complications, severe renal or liver insufficiency, agitated patient, patients under blood pressure-elevating substances \>24h after stroke, patients that need decompressive craniectomy )
• Heart failure defined as known congestive heart failure (CHF) functional class NYHA III-IV (New York Heart Association) OR CHF NYHA II and hospitalization caused by CHF in the preceding 24 months
• OR left ventricular ejection fraction lower or equal 45% either known from preceding imaging method or found at the routine examination (echocardiography) during hospitalization
• Oxygen supply \> 2 l/min during day and night
• Intermediate AHI value: ≥ 5/h and ≤ 20/h
• Known progressive neurological diseases (such as dementia, Parkinson's disease or multiple sclerosis)
• Drug or alcohol abuse (\>14 units alcohol / week for males, \>7 units alcohol / week for females)
• Inability to follow study procedure
• Pregnancy
• Any given contraindications to MRI or MRI-contrast agent (allergy or severe renal impairment)

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Swiss National Science Foundation: collaborator
• TROPOS Stiftung für Humane Verhaltensforschung: collaborator

Study Sites (6)

Clinic universitaire de physiologie, sommeil et exercice, Centre Hospitalier Universitaire (CHU) de Grenoble

Grenoble, 38043, France

Location

Department and Out-Patient Care of Neurology, Charité Center Neurology, Neurosurgery and Psychiatry CC 15, Department of Neurology with Experimental Neurology, Center for Stroke Research Berlin (CSB)

Berlin, 10117, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, HNO-Universitätsklinik, Klinik und Poliklinik für Neurologie

Mainz, 55131, Germany

Location

Federal State Budgetary Institution "Almazov National Medical Research Centre" of the Ministry of Health of the Russian Federation

Saint Petersburg, 197341, Russia

Location

Department of Neurology, Pulmonary Medicine and Institute of Diagnostic and Interventional Neuroradiology, Bern University Hospital

Bern, 3010, Switzerland

Location

Neurology Department, Cantonal Hospital St.Gallen

Sankt Gallen, 9007, Switzerland

Location

Related Publications (11)

• Brown DL, Chervin RD, Kalbfleisch JD, Zupancic MJ, Migda EM, Svatikova A, Concannon M, Martin C, Weatherwax KJ, Morgenstern LB. Sleep apnea treatment after stroke (SATS) trial: is it feasible? J Stroke Cerebrovasc Dis. 2013 Nov;22(8):1216-24. doi: 10.1016/j.jstrokecerebrovasdis.2011.06.010. Epub 2011 Jul 23.

  PMID: 21784661 BACKGROUND

• Tomfohr LM, Hemmen T, Natarajan L, Ancoli-Israel S, Loredo JS, Heaton RK, Bardwell W, Mills PJ, Lee RR, Dimsdale JE. Continuous positive airway pressure for treatment of obstructive sleep apnea in stroke survivors: what do we really know? Stroke. 2012 Nov;43(11):3118-23. doi: 10.1161/STROKEAHA.112.666248. Epub 2012 Sep 27. No abstract available.

  PMID: 23019248 BACKGROUND

• Duss SB, Brill AK, Baillieul S, Horvath T, Zubler F, Flugel D, Kagi G, Benz G, Bernasconi C, Ott SR, Korostovtseva L, Sviryaev Y, Salih F, Endres M, Tamisier R, Gouveris H, Winter Y, Denier N, Wiest R, Arnold M, Schmidt MH, Pepin JL, Bassetti CLA. Effect of early sleep apnoea treatment with adaptive servo-ventilation in acute stroke patients on cerebral lesion evolution and neurological outcomes: study protocol for a multicentre, randomized controlled, rater-blinded, clinical trial (eSATIS: early Sleep Apnoea Treatment in Stroke). Trials. 2021 Jan 22;22(1):83. doi: 10.1186/s13063-020-04977-w.

  PMID: 33482893 BACKGROUND

• Brill AK, Rosti R, Hefti JP, Bassetti C, Gugger M, Ott SR. Adaptive servo-ventilation as treatment of persistent central sleep apnea in post-acute ischemic stroke patients. Sleep Med. 2014 Nov;15(11):1309-13. doi: 10.1016/j.sleep.2014.06.013. Epub 2014 Aug 1.

  PMID: 25190260 RESULT

• Bravata DM, Concato J, Fried T, Ranjbar N, Sadarangani T, McClain V, Struve F, Zygmunt L, Knight HJ, Lo A, Richerson GB, Gorman M, Williams LS, Brass LM, Agostini J, Mohsenin V, Roux F, Yaggi HK. Continuous positive airway pressure: evaluation of a novel therapy for patients with acute ischemic stroke. Sleep. 2011 Sep 1;34(9):1271-7. doi: 10.5665/SLEEP.1254.

  PMID: 21886365 RESULT

• Parra O, Sanchez-Armengol A, Bonnin M, Arboix A, Campos-Rodriguez F, Perez-Ronchel J, Duran-Cantolla J, de la Torre G, Gonzalez Marcos JR, de la Pena M, Carmen Jimenez M, Masa F, Casado I, Luz Alonso M, Macarron JL. Early treatment of obstructive apnoea and stroke outcome: a randomised controlled trial. Eur Respir J. 2011 May;37(5):1128-36. doi: 10.1183/09031936.00034410. Epub 2010 Sep 16.

  PMID: 20847081 RESULT

• Minnerup J, Ritter MA, Wersching H, Kemmling A, Okegwo A, Schmidt A, Schilling M, Ringelstein EB, Schabitz WR, Young P, Dziewas R. Continuous positive airway pressure ventilation for acute ischemic stroke: a randomized feasibility study. Stroke. 2012 Apr;43(4):1137-9. doi: 10.1161/STROKEAHA.111.637611. Epub 2011 Dec 22.

  PMID: 22198979 RESULT

• Ryan CM, Bayley M, Green R, Murray BJ, Bradley TD. Influence of continuous positive airway pressure on outcomes of rehabilitation in stroke patients with obstructive sleep apnea. Stroke. 2011 Apr;42(4):1062-7. doi: 10.1161/STROKEAHA.110.597468. Epub 2011 Mar 3.

  PMID: 21372306 RESULT

• Barbe F, Duran-Cantolla J, Sanchez-de-la-Torre M, Martinez-Alonso M, Carmona C, Barcelo A, Chiner E, Masa JF, Gonzalez M, Marin JM, Garcia-Rio F, Diaz de Atauri J, Teran J, Mayos M, de la Pena M, Monasterio C, del Campo F, Montserrat JM; Spanish Sleep And Breathing Network. Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial. JAMA. 2012 May 23;307(20):2161-8. doi: 10.1001/jama.2012.4366.

  PMID: 22618923 RESULT

• Craig SE, Kohler M, Nicoll D, Bratton DJ, Nunn A, Davies R, Stradling J. Continuous positive airway pressure improves sleepiness but not calculated vascular risk in patients with minimally symptomatic obstructive sleep apnoea: the MOSAIC randomised controlled trial. Thorax. 2012 Dec;67(12):1090-6. doi: 10.1136/thoraxjnl-2012-202178. Epub 2012 Oct 30.

  PMID: 23111478 RESULT

• Marin JM, Agusti A, Villar I, Forner M, Nieto D, Carrizo SJ, Barbe F, Vicente E, Wei Y, Nieto FJ, Jelic S. Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA. 2012 May 23;307(20):2169-76. doi: 10.1001/jama.2012.3418.

  PMID: 22618924 RESULT

Related Links

• trials webpage

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Sleep Apnea, Central; Stroke; Sleep Apnea Syndromes

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Claudio L Bassetti

  Department of Neurology, Bern University Hospital, 3010 Bern, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2015
• First Posted: September 18, 2015
• Study Start: August 13, 2015
• Primary Completion: March 5, 2022
• Study Completion: November 1, 2022
• Last Updated: June 29, 2022

Record last verified: 2022-06

Locations

FR (1); DE (2); RU (1); CH (2)