Apnea, Stroke and Incident Cardiovascular Events

Stroke Clinical Trial

— ASCENT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04399200
• Other study ID #: 2019-A03085-52
• Secondary ID: 2019-A03085-52
• Status: Recruiting
• Start date: July 13, 2020
• Est. completion date: June 1, 2035

Study information

• Verified date: May 2022
• Source: University Hospital, Grenoble
• Contact: Sébastien Baillieul, MD, MSc
• Phone: +33 (0)4 76 76 87 66
• Email: sbaillieul[@]chu-grenoble.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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 4 to 7): 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1620
• Est. completion date: June 1, 2035
• Est. primary completion date: June 1, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Apnea
• Fragmentation, Sleep
• Respiratory Aspiration
• Sleep Apnea Syndromes
• Sleep Apnea, Central
• Sleep Apnea, Obstructive
• Sleep Deprivation
• Sleep-disordered Breathing
• Stroke
• Syndrome

Intervention

Device:
• 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)

Locations

Country	Name	City	State
France	University Hospital Grenoble	Grenoble

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Grenoble

Country where clinical trial is conducted

France, 

References & Publications (50)

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* Note: There are 50 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of Major Adverse Cardiac or Cerebrovascular Events (MACCEs)	Composite endpoint composed of cardiac or cerebrovascular events regrouping: death from cardiac of cerebrovascular cause, non fatal stroke (either ischemic or hemorrhagic), and non-fatal acute coronary disease	1 year after SDB diagnosis
Secondary	Prevalence of Major Adverse Cardiac or Cerebrovascular Events (MACCEs)	Composite endpoint composed of cardiac or cerebrovascular events regrouping: death from cardiac of cerebrovascular cause, non fatal stroke (either ischemic or hemorrhagic), and non-fatal acute coronary disease	5 years after SDB diagnosis
Secondary	Prevalence of secondary cardiac or cerebrovascular events	Composite endpoint composed of cardiac or cerebrovascular events regrouping: transient ischemic attack (TIA), any acute coronary disease, hospitalization for any cardio-vascular cause and peripheral artery disease	5 years after SDB diagnosis
Secondary	Change in BMI from inclusion to 5 years	Change in body mass index (BMI), defined as weight (Kg)/height (m)². This will be calculated at inclusion and at each visit	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Change in waist, neck, and abdominal circumferences, from inclusion visit to 5 years	Change in waist, neck and abdominal circumferences in cm. This will be measured at inclusion and at each visit.	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Change in NIHSS score from inclusion to 5 years	Stroke severity assessed by National Institute of Health Stroke Scale (NIHSS). This tool is composed of 15 items, each assessing specific abilities. (0: no stroke symptoms; 1 to 4: minor stroke; 5 to 15: moderate stroke; 16-20: moderate to severe stroke; >20 : severe stroke). The scale will be administered at each visit.	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	ABCD² score at inclusion	Score evaluating the risk for stroke after a transient ischemic attack (TIA). The scale ranges from 0 (low level) to 7 (high level). 0 to 3: low risk; 4 to 5: moderate, 6 to 7: high risk	at inclusion
Secondary	Clinical outcome: change in modified Ranking Sale (mRS) from inclusion to 5 years	Scale assessing functional outcome after stroke, ranging from 0 (no symptoms at all) to 5 (severe disability), measured at each visit	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Clinical outcome: change in Functional Independence Measure (FIM) from inclusion to 5 years	Scale assessing functional outcome after stroke, ranging from 18 (totally dependent) to 126 (totally independent), measured at each visit	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Clinical outcome: change in Stroke Impact Scale (SIS-16) from inclusion to 5 years	This scale assess patient's health after stroke, through 16 items evaluating functional independence and mobility. This scale ranges from 16 (total independance) to 80 (total dependancy). The scale will be administer at each visit	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Clinical outcome: change Patient Health Questionnaire (PHQ-9) from inclusion to 5 years	Scale assessing patient's depression symptoms, administered at each visit. The scale ranges from 0 (no depression) to 27 (severe depression).	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Clinical outcome: change Fugl-Meyer Assessment Scale from inclusion to 5 years	Scale assessing sensori-motor upper extremity function in post-stroke patients, administered at each visit. The maximal possible score is 226, which corresponds to a complete sensori-motor recovery.	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Change in walking and locomotion abilities: nFAC score, from inclusion to 5 years	Evaluation of ambulation abilities, from 0 (cannot walk) to 8 (able to walk independantly)	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Change in walking and locomotion abilities: 10m walking test, from inclusion to 5 years	Evaluation of speed on the 10m walking test	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Change in daytime sleepiness: score on the Epworth Sleepiness Scale, from inclusion to 5 years	Daytime sleepiness score measured by Epworth Sleepiness Scale. The scale ranges from 0 (no sleepiness) to 24 (severe sleepiness)	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Change in daytime sleepiness: score Berlin Questionnaire for Sleep Apnea (BQSA)	Sleep apnea screening questionnaire that identifies the risk (from low to high) of sleep disordered breathing	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Assessment of sleep and fatigue: score change on Chalder Fatigue Scale from inclusion to 5 years	Questionnaire evaluating the severity of tiredness, on a scale ranging from 0 (no fatigue) to 33 (severe), administered at each visit	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Assessment of sleep and fatigue: score change on Fatigue Severity Scale (FSS) from inclusion to 5 years	Questionnaire evaluating the severity of tiredness, on a scale ranging from 9 (no fatigue) to 63 (severe), administered at each visit	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Assessment of sleep and fatigue: score change on Pichot's Fatigue Scale from inclusion to 5 years	Questionnaire evaluating the severity of tiredness, on a scale ranging from 0 (no fatigue) to 32 (severe), administered at each visit	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Change in depression symptoms from inclusion to 5 years : Pichot's Depression Scale (QD2A)	Questionnaire evaluating depression symptoms through right/false responses to 13 items, administered at each visit (score: 0 to 13)	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Change in cognitive abilities from inclusion to 5 years: scores on the Montreal Cognitive Assessment Test	Global assessment of cognitive functions, evaluating on 30 points and in 10 minutes short-term memory, verbal fluency, visuoconstructive abilities, executive functions, attention, working memory, language and spatiotemporal orientation. The test will be administered at each visit.	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Change in cognitive abilities from inclusion to 5 years : scores on the Frontal Assessment Battery	Short screening test evaluating executive function, on a scale from 0 (severe disability) to 18 (no disability)	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Change in cognitive abilities from inclusion to 5 years : Language Screening Test (LAST)	Rapid evaluation of language abilities (oral expression and comprehension) through 15 items (total score: 15).	at inclusion, and at each visit up to 5 years after SDB diagnosis
Secondary	Prevalence of SDB assessed by polysomnography	Prevalence of SDB, assessed by polysomnography, and defined as AHI (Apnea-Hypopnea Index >15/h)	3 months post-stroke
Secondary	Prevalence of respiratory disorders	Respiratory assessments : spirometry, plethysmography, CO diffusion, blood gas measurement, measurement of ventilatory response to CO2	3 months post-stroke
Secondary	Change in adherence to SDB treatments, from 6 months to 5 years after SDB diagnosis	Treatment adherence, assessed by CPAP monitoring (mean hours/night) if applicable	from 6 months and at each visit up to 5 years after SDB diagnosis
Secondary	Stroke characteristics : lesion volume	Stroke volume in mm3, determined on MRI/CT scan	At inclusion
Secondary	Concentration of C-Reactive protein	Concentration of C-Reactive protein by blood sampling	3 months
Secondary	Change in degree of carotid stenosis (ancillary study)	NASCET (North American Symptomatic Carotid Endarterectomy) evaluation of carotid stenosis in percent by Echo-doppler	from 3 months to 5 years after SDB diagnosis
Secondary	Change in intima-media thickness (ancillary study) from 3 months to 5 years	Measurement of carotid intima-media thickness (in mm) by Echo-Doppler	from 3 months to 5 years after SDB diagnosis
Secondary	Plasmatic and urinary miRNAs (ancillary study)	miRNA expression and modulation in plasma and urine	from 3 months to 5 years after SDB diagnosis
Secondary	miRNAs in carotid artery plaque (ancillary study)	miARNs expression and modulation in carotid artery plaque	At baseline (carotid surgery)
Secondary	Prevalence of post-operative complication (ancillary study)	Prevalence of post-operative complication defined as post-operative hematomy, nerve palsy of nerves X and XII, per - post-operative ischemic or hemorragic strokes, myocardial infarction, death	from 3 months to 5 years after SDB diagnosis
Secondary	Adipose tissue analysis (ancillary study)	Morphological analysis of adipose tissue collected during endarteriectomy, expression of membrane and lipidic and glycemic markers, expression of inflammatory markers	At baseline (carotid surgery)