Apnea, Stroke and Incident Cardiovascular Events

Официальное название

Sleep Apnea Syndrome and Incidence of Major Adverse Cardiac and Cerebrovascular Events (MACCEs) After a First Stroke

Обзор

This prospective cohort study aims to compare the proportion of cardiac or cerebrovascular events after a first stroke, a first transient ischemic attack (TIA) or recurrent TIA, between sleep-disordered breathing (SDB) and non-SDB (control) patients, one year after SDB diagnosis, performed 3 months after stroke onset. The primary outcome is a composite endpoint composed of cardiac or cerebrovascular events regrouping: death from any cardiac or cerebrovascular cause, non-fatal stroke, and non-fatal acute coronary disease. 1620 patients, in the acute phase of a first stroke, TIA or recurrent TIA will be included in the cohort. Clinical, neuroimaging, sensorimotor, cognitive and biological parameters will be collected at inclusion. Three months after stroke or TIA onset, polysomnography will be performed for SDB diagnosis. Patients will be considered as having SDB for an Apnea-Hypopnea Index (AHI) \> 15 events/hour, or to the control group otherwise. The same clinical, imaging, cognitive and biological assessments than during the first visit will be performed; incident (new) cardiovascular events will be collected. Three months later, and at 1, 2, 3, 4 and 5 years after SDB diagnosis, the same clinical, cognitive, sensorimotor, and sleep-related evaluations will be performed. In addition to the aforementioned parameters, incident cardiovascular outcomes will be collected, at the same time points. The primary study outcome will be retrieved one year after stroke onset.

Подробное описание

This is a prospective cohort study that aims at comparing the proportion of incident cardiovascular events after a first stroke, first transient ischemic attack (TIA) or recurrent TIA, between sleep-disordered breathing patients (SDB, defined as an apnea-hypopnea index \> 15 events/hour) and non-SDB patients, one year after SDB diagnosis performed by polysomnography 3 months after the cerebrovascular event.

The primary outcome is a composite endpoint composed of cardiac or cerebrovascular events (Major Adverse Cardiovascular Events, MACCEs), regrouping: death from any cardiac or cerebrovascular cause, non-fatal stroke, non-fatal acute coronary event. Secondary outcomes include secondary cardiac and cerebrovascular events; stroke-related functional criteria; lesion-related criteria obtained from morphological MRI; scores on questionnaires assessing the quality of life, depression and sleep; functional, cognitive and sensorimotor evaluations; locomotion tests; and sleep-related criteria.

1620 patients, aged 18 to 85 years, in the acute phase (\<72h) of a first stroke, first or recurrent TIA, and with a score on the modified Rankin Scale (mRS) ≤1 before stroke onset, will be included in the cohort. All patients included in the study will be followed for 5 years. The schedule of follow-up will be as follow :

* Selection visit (Days 0 to 3): verification of eligibility criteria, patients' or relatives' information, informed consent signature. * Inclusion visit (Days 1 to 180): clinical history and treatments, clinical evaluation and anthropometrical parameters, stroke-related criteria (including score on the National Institute of Health Stroke Scale), functional, cognitive, and sensorimotor evaluation, walking and locomotion tests, questionnaires, stroke imagery by magnetic resonance imagery, blood sampling. * SDB diagnosis (Month 3): the same clinical, MRI and biological parameters will be collected and the same questionnaires will be fulfilled by the patients. In addition, they will undergo polysomnography to assess their SDB status. Patients will be assigned to the SDB group if the AHI \> 15 events/hour; otherwise they will be assigned to the control group. Patients assigned to the SDB group will be proposed a treatment for their SDB according to standard care procedures. * Clinical follow-up: sleep and neurological; (initial 3 months and then annually after SDB diagnosis up to 5 years after SDB diagnosis): retrieval of new cardiac or cerebrovascular events (primary study outcome (MACCEs)), stroke-related parameters, questionnaires, functional, cognitive, and sensorimotor evaluations, locomotion tests, sleep follow-up (adherence to SDB treatment, tolerance, efficacy). Biological sampling will also be done at 1, 2 and 5 years after SDB diagnosis.

Ancillary study - CAtSS (Carotid, Atherosclerosis, Stroke and Sleep apnea) Conjointly to the previously described ASCENT protocol, an ancillary study will be proposed to the subgroup of patients eligible for carotid surgery (endarterectomy) following their cerebrovascular event.

The purpose of this ancillary study is to evaluate the impact of SDB and SDB treatment on the evolution of the carotid plaque after surgery. For the patients who accepted to participate to this ancillary study, the degree of carotid stenosis and the artery wall thickness (intima-media thickness, assessed by echo-Doppler) will be measured during the inclusion visit, at 3 months, 6 months, and at each annual visit. During surgery, a fragment of carotid plaque will be kept for morphologic and histologic analyses as well as miRNAs dosing, miARNs being recognized as indicators of carotid plaque instability. Plasmatic and urine samples will also be collected for miRNA analyses.

Вмешательства

• Устройство Treatment according to standard care recommandation
  SDB treatment according to standard care recommandation: Continuous Positive Airway Pressure (CPAP), Mandibular Advancement Device, Positionnal Therapy, Adaptive Servo-Ventilation (ASV), Non-Invasive Ventilation (NIV)

Первичные конечные точки

• Prevalence of Major Adverse Cardiac or Cerebrovascular Events (MACCEs) [Срок оценки: 1 year after SDB diagnosis]

Вторичные конечные точки (12)

• Prevalence of Major Adverse Cardiac or Cerebrovascular Events (MACCEs) [Срок оценки: 5 years after SDB diagnosis]
• Prevalence of secondary cardiac or cerebrovascular events [Срок оценки: 5 years after SDB diagnosis]
• Change in BMI from inclusion to 5 years [Срок оценки: at inclusion, and at each visit up to 5 years after SDB diagnosis]
• Change in waist, neck, and abdominal circumferences, from inclusion visit to 5 years [Срок оценки: at inclusion, and at each visit up to 5 years after SDB diagnosis]
• Change in NIHSS score from inclusion to 5 years [Срок оценки: at inclusion, and at each visit up to 5 years after SDB diagnosis]
• ABCD² score at inclusion [Срок оценки: at inclusion]
• Clinical outcome: change in modified Ranking Sale (mRS) from inclusion to 5 years [Срок оценки: at inclusion, and at each visit up to 5 years after SDB diagnosis]
• Clinical outcome: change in Functional Independence Measure (FIM) from inclusion to 5 years [Срок оценки: at inclusion, and at each visit up to 5 years after SDB diagnosis]
• Clinical outcome: change in Stroke Impact Scale (SIS-16) from inclusion to 5 years [Срок оценки: at inclusion, and at each visit up to 5 years after SDB diagnosis]
• Clinical outcome: change Patient Health Questionnaire (PHQ-9) from inclusion to 5 years [Срок оценки: at inclusion, and at each visit up to 5 years after SDB diagnosis]
• Clinical outcome: change Fugl-Meyer Assessment Scale from inclusion to 5 years [Срок оценки: at inclusion, and at each visit up to 5 years after SDB diagnosis]
• Change in walking and locomotion abilities: nFAC score, from inclusion to 5 years [Срок оценки: at inclusion, and at each visit up to 5 years after SDB diagnosis]

Критерии участия

Критерии включения

• Male or female, aged 18 to 85 years
• Admitted in the stroke unit no later than 72h after the onset of stroke symptoms:

• First stroke confirmed by computed tomography scan or magnetic resonance imaging, whatever the localization
• Initial or recurrent TIA, as defined by a brief and sudden neurological dysfunction for which an ischemic cause is presumed, with symptoms lasting less than 24 hours, and/or with no visible lesion on neuroimaging evaluation.
• Score on the Modified Ranking scale (mRS) ≤1 before stroke
• Signed informed consent by patient or his/her relative if not able
• Patient eligible to carotid endarterectomy (for ancillary study only)

Критерии исключения

• Pregnant or breastfeeding women
• Past history of stroke
• Inability to follow rehabilitation procedure
• Patients with ongoing treatment for SDB
• Exclusion period for another study
• Patients not affiliated to a French social and health insurance system or equivalent
• Prisoners or patients who require protection by the law

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Франция · 1 центр

• University Hospital Grenoble — Grenoble

Публикации

• GBD 2016 Stroke Collaborators. Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 May;18(5):439-458. doi: 10.1016/S1474-4422(19)30034-1. Epub 2019 Mar 11. PMID 30871944
• Javaheri S, Barbe F, Campos-Rodriguez F, Dempsey JA, Khayat R, Javaheri S, Malhotra A, Martinez-Garcia MA, Mehra R, Pack AI, Polotsky VY, Redline S, Somers VK. Sleep Apnea: Types, Mechanisms, and Clinical Cardiovascular Consequences. J Am Coll Cardiol. 2017 Feb 21;69(7):841-858. doi: 10.1016/j.jacc.2016.11.069. PMID 28209226
• Hermann DM, Bassetti CL. Role of sleep-disordered breathing and sleep-wake disturbances for stroke and stroke recovery. Neurology. 2016 Sep 27;87(13):1407-16. doi: 10.1212/WNL.0000000000003037. Epub 2016 Aug 3. PMID 27488603
• Seiler A, Camilo M, Korostovtseva L, Haynes AG, Brill AK, Horvath T, Egger M, Bassetti CL. Prevalence of sleep-disordered breathing after stroke and TIA: A meta-analysis. Neurology. 2019 Feb 12;92(7):e648-e654. doi: 10.1212/WNL.0000000000006904. Epub 2019 Jan 11. PMID 30635478
• Lisabeth LD, Sanchez BN, Lim D, Chervin RD, Case E, Morgenstern LB, Tower S, Brown DL. Sleep-disordered breathing and poststroke outcomes. Ann Neurol. 2019 Aug;86(2):241-250. doi: 10.1002/ana.25515. Epub 2019 Jun 19. PMID 31155749
• Brill AK, Horvath T, Seiler A, Camilo M, Haynes AG, Ott SR, Egger M, Bassetti CL. CPAP as treatment of sleep apnea after stroke: A meta-analysis of randomized trials. Neurology. 2018 Apr 3;90(14):e1222-e1230. doi: 10.1212/WNL.0000000000005262. Epub 2018 Mar 9. PMID 29523641
• Amarenco P, Lavallee PC, Labreuche J, Albers GW, Bornstein NM, Canhao P, Caplan LR, Donnan GA, Ferro JM, Hennerici MG, Molina C, Rothwell PM, Sissani L, Skoloudik D, Steg PG, Touboul PJ, Uchiyama S, Vicaut E, Wong LK; TIAregistry.org Investigators. One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke. N Engl J Med. 2016 Apr 21;374(16):1533-42. doi: 10.1056/NEJMoa1412981. PMID 27096581
• Amarenco P, Lavallee PC, Monteiro Tavares L, Labreuche J, Albers GW, Abboud H, Anticoli S, Audebert H, Bornstein NM, Caplan LR, Correia M, Donnan GA, Ferro JM, Gongora-Rivera F, Heide W, Hennerici MG, Kelly PJ, Kral M, Lin HF, Molina C, Park JM, Purroy F, Rothwell PM, Segura T, Skoloudik D, Steg PG, Touboul PJ, Uchiyama S, Vicaut E, Wang Y, Wong LKS; TIAregistry.org Investigators. Five-Year Risk o PMID 29766771

Идентификаторы

NCT: NCT04399200 · 2019-A03085-52 · 2019-A03085-52

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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