Sleep Apnea in TIA/Stroke: Reducing Cardiovascular Risk With Positive Airway Pressure

NCT01446913 | Completed Results DMC

• 2 other identifiers: 1101007811U34HL105285-01
• Study Type: interventional
• Target: 255
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this study is to develop a novel study design to safely and ethically conduct a long-term randomized controlled trial among patients at high risk for both sleep apnea and cardiovascular events that will examine whether effective positive airway pressure(PAP) therapy reduces cardiovascular risk. Patients with transient ischemic attack(TIA) or stroke have a high prevalence of sleep apnea(60-80%), and they are at high risk of cardiovascular events(myocardial infarction, congestive heart failure, recurrent stroke, and cardiovascular death)in the first year post event, despite current prevent strategies. Therefore, the treatment of sleep apnea may represent a novel therapeutic target to reduce cardiovascular outcomes in this high risk population.

Conditions

Transient Ischemic Attack; Stroke

Keywords

Sleep Apnea; CPAP adherence; behavioral adherence; stroke

Outcome Measures

Primary Outcomes (9)

• HOMA IR Change From Baseline

  The homeostasis model assessment-estimated insulin resistance (HOMA-IR). HOMA IR change is one of the measures used to assess cardiovascular risk. HOMA-IR Index (measured by calculating - fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5.). The change from baseline up until the final measurement (up to 12 months) was assessed.

  Baseline and up to 12 months

• CRP Change From Baseline

  C-reactive protein (CRP) is a blood test marker for inflammation in the body. CRP is produced in the liver and its level is measured by testing the blood. CRP is classified as an acute phase reactant, which means that its levels will rise in response to inflammation. CRP is one of the measures used to assess cardiovascular risk. The change from baseline up until the final measurement (up to 12 months) was assessed.

  Baseline and up to 12 months

• IL-6 Change From Baseline

  IL-6 is a type of protein known as a cytokine, produced by cells of the immune system in response to an infection. IL-6 test results measure the amount of IL-6 circulating in the blood and are used as one sign of systemic inflammation. Il-6 is one of the measures used to assess cardiovascular risk. The change from baseline up until the final measurement (up to 12 months) was assessed.

  Baseline and up to 12 months

• Catecholamine Change From Baseline

  Catecholamine testing measures the amounts of catecholamines which are a group of similar substances/hormones released into the blood in response to physical or emotional stress. The primary catecholamines are dopamine, epinephrine (adrenaline), and norepinephrine. Catecholamine is one of the measures used to assess cardiovascular risk. The change from baseline up until the final measurement (up to 12 months) was assessed.

  Baseline and up to 12 months

• Heart Rate Variability Change From Baseline

  Heart rate variability (HRV) is the constant variation in milliseconds between heartbeats. HRV is one of the measures used to assess cardiovascular risk. The change from baseline up until the final measurement (up to 12 months) was assessed.

  Baseline and up to 12 months

• 24-H Systolic Blood Pressure Mean Change From Baseline

  24-H Systolic Blood Pressure is one of the measures used to assess cardiovascular risk- this was assessed multiple times and averaged across a in 24 hour time period. The change from baseline up until the final measurement (up to 12 months) was assessed.

  Baseline and up to 12 months

• Flow-mediated Vasodilation Mean Change From Baseline

  Flow-mediated vasodilation is performed when the brachial artery diameter is measured (in mm) during three conditions; baseline (after at least 10 min supine rest), during reactive hyperaemia (induced by inflation to 250 mmHg and then deflation of a sphygmomanometer cuff around the forearm) and finally after the administration of sublingual nitroglycerin. A linear array, high resolution ultrasound transducer is used to provide B-mode images of the target vessel, proximal to the forearm cuff. Flow-mediated vasodilation is one of the measures used to assess cardiovascular risk and the mean of the change in the multiple measurements was used at each time point. The change from baseline up until the final measurement (up to 12 months) was assessed.

  Baseline to up to 12 months

• Carotid Intima-Medial Thickness Mean Change From Baseline

  Carotid Intima-Medial Thickness are measurements of the mean values of Intima-media thickness (IMT) of carotid arteries. Caroid Intima-Medial Thickness mean change is one of the measures used to assess cardiovascular risk. The change from baseline up until the final measurement (up to 12 months) was assessed.

  Baseline to up to 12 months

• CPAP Adherence Rates Change From Baseline

  CPAP adherence rates were calculated as hours of CPAP use per night. The change from baseline up until the final measurement (up to 12 months) was assessed. The Respironics M-series (now System One, Phillips Respironics, North Ryde, Australia) produced a record of the patient adherence (hours of use per night) throughout the duration of the follow up period.

  Baseline to up to 12 months

Secondary Outcomes (9)

• HOMA IR Change From Baseline With CPAP Use

  Baseline to up to 12 months

• CRP Change From Baseline With CPAP Use

  Baseline to up to 12 months

• IL-6 Change From Baseline With CPAP Use

  Baseline to up to 12 months

• Catecholamine Change From Baseline With CPAP Use

  Baseline to up to 12 months

• Heart Rate Variability Change From Baseline With CPAP Use

  Baseline to up to 12 months

Study Arms (3)

Standard Intervention group

ACTIVE COMPARATOR

This group gets unattended sleep study, auto titrating CPAP, and standard CPAP support.

Device: Standard CPAP Intervention

Enhanced CPAP intervention

ACTIVE COMPARATOR

This group gets an unattended sleep study, autotitrating CPAP, and enhanced CPAP support.

Behavioral: Enhanced CPAP Intervention

Usual Care

NO INTERVENTION

This group usual care after TIA/stroke and a sleep study at the end of the study.

Interventions

Standard CPAP Intervention DEVICE

Standard Intervention group

Enhanced CPAP Intervention BEHAVIORAL

Enhanced CPAP intervention

Eligibility Criteria

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

You may qualify if:

• years and older
• TIA or ischemic stroke
• within 1 week of neurological symptom onset
• brain imaging within 24 hours

You may not qualify if:

• known to have sleep apnea
• suspected sleep disorder other than sleep apnea
• hospice patients or patients receiving comfort only measures
• patients unable to use a nasal or face mask
• patients who require mechanical ventilation
• Non English language patients
• inability to provide informed consent
• active suicidal ideation
• live outside the recruitment area
• provider does not allow researcher to contact patient

Sponsors & Collaborators

• Yale University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Indiana University: collaborator

Study Sites (2)

Yale University

New Haven, Connecticut, 06511, United States

Location

University of Indiana

Indianapolis, Indiana, 46202, United States

Location

Related Publications (2)

• Koo BB, Bravata DM, Tobias LA, Mackey JS, Miech EJ, Matthias MS, Stahl SM, Sico JJ, Vaz Fragoso CA, Williams LS, Lampert R, Qin L, Yaggi HK. Observational Study of Obstructive Sleep Apnea in Wake-Up Stroke: The SLEEP TIGHT Study. Cerebrovasc Dis. 2016;41(5-6):233-41. doi: 10.1159/000440736. Epub 2016 Jan 27.

  PMID: 26811929 BACKGROUND

• Yaggi HK, Mittleman MA, Bravata DM, Concato J, Ware J, Stoney CM, Redline S. Reducing cardiovascular risk through treatment of obstructive sleep apnea: 2 methodological approaches. Am Heart J. 2016 Feb;172:135-43. doi: 10.1016/j.ahj.2015.07.033. Epub 2015 Sep 11.

  PMID: 26856225 DERIVED

MeSH Terms

Conditions

Ischemic Attack, Transient; Stroke; Sleep Apnea Syndromes

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

A study design which compares the effectiveness of a diagnostic and treatment strategy to usual care may result in an underestimate of the efficacy and potency of CPAP on our outcomes. Not all patients in the intervention strategy had sleep apnea.

Results Point of Contact

• Title: Henry Klar Yaggi, MD (PI)
• Organization: Yale University School of medicine

henry.yaggi@yale.edu

203-785-4163

Study Officials

• Henry Yaggi, MD,MPH

  Yale University

  PRINCIPAL INVESTIGATOR

• Dawn M Bravata, M.D.

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2011
• First Posted: October 5, 2011
• Study Start: May 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: April 1, 2014
• Last Updated: November 18, 2020
• Results First Posted: November 18, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share

Locations

US (2)