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

This study is currently recruiting participants.
Verified November 2013 by Yale University
Sponsor:
Collaborators:
Indiana University
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT01446913
First received: October 3, 2011
Last updated: November 12, 2013
Last verified: November 2013

October 3, 2011
November 12, 2013
May 2011
December 2013   (final data collection date for primary outcome measure)
  • To evaluate whether a diagnosis and treatment intervention strategy for sleep apnea results in a significant reduction in five domains of cardiovascular risk markers (inflammatory, autonomic, insulin resistance, endothelial, and atherosclerotic). [ Time Frame: Change from baseline to final measurements (6-12 months) ] [ Designated as safety issue: No ]
    The primary outcomes will include: (a) the impact of CPAP on pathophysiologic markers in the following domains of cardiovascular risk: inflammation (CRP, Il-6), heightened sympathetic activity/parasympathetic withdrawal (plasma catecholamine and heart rate variability (HRV)), insulin resistance (HOMA-IR), endothelial injury (flow mediated vasodilation), and atherosclerosis (carotid intima-media thickness). This analysis will include both an intention to treat analysis for all randomized patients as well as a pre-specified subgroup analysis of only patients with sleep apnea.
  • To determine the level of CPAP adherence that corresponds to greatest improvements in markers of cardiovascular risk. [ Time Frame: Change from baseline to final measurements (6-12 months) ] [ Designated as safety issue: No ]
    The comparison of change in biomarkers at the time of final measurement between CPAP adherence groups will be restricted to intervention patients with sleep apnea (both the enhanced protocol and the standard protocol patients). We will use mixed models with random effect of patients to test for differences among three CPAP adherence groups (good CPAP use, some CPAP use and no CPAP use, adjusting for follow-up length (in months) (possible interaction term of follow-up length and CPAP adherence groups), site, and TIA/stroke strata. If the overall estimate of the effect for adherence group is statistically significant, we will further assess the differences between pairs of groups (good CPAP use vs. some CPAP use, some CPAP use vs. no CPAP use, and good CPAP use vs. no CPAP use).
  • To determine whether an enhanced intervention protocol (targeted education, customized cognitive intervention, increased CPAP support) will result in improved long-term CPAP adherence rates among patients with sleep apnea. [ Time Frame: baseline to final measurements (6-12 months) ] [ Designated as safety issue: No ]
    This analysis will be restricted to intervention patients with sleep apnea. We will compare the proportion of patients with good CPAP use in the enhanced versus standard protocols, using logistic regression adjusting for follow-up length (in months) (possible interaction term of follow-up length and treatment), site, and TIA/stroke strata. We will report the observed proportions with 95% confidence intervals.
  • Change in Inflammation Markers [ Time Frame: Change from baseline to 12 months ] [ Designated as safety issue: No ]
    Change in C-reactive protein(CRP) and Interleukin-6 (IL-6) levels in the blood.
  • Change in Metabolic Markers [ Time Frame: Change from baseline to 12 months ] [ Designated as safety issue: No ]
    Change in insulin resistance (HOMA-IR)
  • Change in Autonomic Tone [ Time Frame: Change from baseline to 12 months ] [ Designated as safety issue: No ]
    Change in 24-hour blood pressure, plasma catecholamine levels, and heart rate variability measurements.
  • Change in Atherosclerosis Indicators [ Time Frame: Change from baseline to 12 months ] [ Designated as safety issue: No ]
    Change in Carotid Intima-Media Thickness measurements
  • Change in Endothelial Injury Indicators [ Time Frame: Change from baseline to 12 months ] [ Designated as safety issue: No ]
    Change in flow-mediated dilation (FMD) measurements.
Complete list of historical versions of study NCT01446913 on ClinicalTrials.gov Archive Site
  • To collect the vascular event rate as pilot data for a future effectiveness strategy trial of CPAP among patients with TIA and stroke to reduce cardiovascular events and death. [ Time Frame: Baseline to final measurements (6-12 months) ] [ Designated as safety issue: No ]
    We will report the observed vascular event rates (stroke, acute coronary syndrome, and all-cause mortality) in person years (and with 95% confidence intervals) in the intervention patients (both the enhanced protocol and the standard protocol patients) and the control patients. We will not compare these rates with stochastic testing given that this study has not been designed to provide adequate power for this comparison.
  • Examine the relationship between CPAP use and various domains of cardiovascular risk markers and the impact of sleep duration and sleep apnea severity. [ Time Frame: baseline to final assessment (6-12 months) ] [ Designated as safety issue: No ]
    This analysis will be restricted to (definite TIA/Stroke) intervention patients with sleep apnea. We will begin this exploratory analysis by graphing the association between CPAP use (on the x-axis) and the change in the cardiovascular markers (on the y-axis). For these graphical analyses, we will use the following measures of CPAP use: (a) total cumulative hours of CPAP use over the study period (continuous variable in hours); (b) the mean observed hours of CPAP use per night divided by the estimated average hours of sleep per night (continuous variable that ranges from 0 to 100%) (Figure 11). To establish the relationship between CPAP use and cardiovascular markers we may then engage in regression modeling, controlling for site, and TIA/stroke strata. Analyses will be conducted for all subjects, and by AHI severity groups (5-15, 15-30, ≥ 30).
  • 24 hour blood pressure measurements [ Time Frame: basleine to final assessments (6-12 months) ] [ Designated as safety issue: No ]
    We will use similar ANCOVA as in primary analysis plan to analyze: (a) mean 24-hour systolic, diastolic BP; (b) the defined daily dose (DDD) of antihypertensive medications (which is defined as the average maintenance dose per day for a drug used for its main indication in adults (http://www.whocc.no/atcdd/)); (c) medication-adjusted 24-hour SBP, which is calculated as [mean 24-hour SBP in mmHg] + [patient's DDD × (8.0 mmHg). We will also use a logistic regression model for the binary outcomes: (a) the patients with a dipping in systolic or diastolic BP ≥ 10% at follow-up or not; and (b) patients with a decrease from baseline to follow-up in 24-hour SBP of 5 mmHg or not, with the independent variables of baseline BP measurements, follow-up time, treatment arms, possible interaction term of time and treatment arms, and baseline characteristics which are clinically different between groups at baseline (p < 0.05).
Determine level of CPAP adherence that correspond to improvements in markers of Cardiovascular risk [ Time Frame: baseline to 1 year ] [ Designated as safety issue: No ]
A dose-response relationship exists such that greater effective long-term CPAP use results in greater improvement in markers of cardiovascular risk
  • Patient-reported measurements [ Time Frame: baseline to final assessments (6-12 months) ] [ Designated as safety issue: No ]
    The analysis will be restricted to patients with sleep apnea. For patient-reported measurements (NIH stroke scale for all, stroke patients and TIA patients, modified Rankin score, Epworth sleepiness scale, and PHQ8), results are summarized by means (standard deviations) and medians (minimum, maximum) will be used. Mixed models will be used where the dependent variables are the measurements baseline and follow-up, and the independent variables are follow-up length (in months), treatment arm and possible interaction term of follow-up length (in months) and treatment arm adjusting for baseline measurement, site and TIA/stroke strata.
  • Safety Analyses [ Time Frame: baseline to final assessments (6-12 months) ] [ Designated as safety issue: Yes ]
    All adverse events will be reported regardless of severity and relationship to CPAP. The incidence of adverse events will be summarized with frequency tables by three treatment arms and receiving CPAP or not.
Not Provided
 
Sleep Apnea in TIA/Stroke: Reducing Cardiovascular Risk With Positive Airway Pressure
Sleep Apnea in TIA/Stroke: Reducing Cardiovascular Risk With Positive Airway Pressure

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.

The proposed study is a randomized controlled trial among patients with transient ischemic attack (TIA) and minor stroke, comparing strategies for the diagnosis and treatment of sleep apnea with usual care over 6-12 months at 2 sites (Yale University School of Medicine and Indiana University School of Medicine). Patients with TIA and minor stroke will be randomly assigned to either usual care or a diagnosis and treatment approach that includes ambulatory polysomnography and initiation of autotitrating CPAP for sleep apnea in a 1:2 (control:intervention) randomization scheme. Intervention patients with sleep apnea will receive either a standard CPAP treatment intervention or an enhanced protocol designed to increase long-term CPAP adherence. The primary outcomes will include: (a) the impact of CPAP on pathophysiologic markers in the following domains of cardiovascular risk: inflammation (CRP, Il-6), heightened sympathetic activity/parasympathetic withdrawal (plasma catecholamines and heart rate variability (HRV)), insulin resistance (HOMA-IR, HbA1C), endothelial injury (flow mediated vasodilation), and atherosclerosis (carotid intima-media thickness); and (b) long-term (6-12 month) CPAP adherence.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
  • Transient Ischemic Attack
  • Stroke
  • Device: Standard CPAP Intervention
  • Behavioral: Enhanced CPAP Intervention
  • Active Comparator: Standard Intervention group
    This group gets unattended sleep study, auto titrating CPAP, and standard CPAP support.
    Intervention: Device: Standard CPAP Intervention
  • Active Comparator: Enhaced CPAP intervention
    This group gets an unattended sleep study, autotitrating CPAP, and enhanced CPAP support.
    Intervention: Behavioral: Enhanced CPAP Intervention
  • No Intervention: Usual Care
    This group usual care after TIA/stroke and a sleep study at the end of the study.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
255
April 2014
December 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

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

Exclusion Criteria:

  • 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
Both
18 Years and older
No
Not Provided
United States
 
NCT01446913
1101007811, U34HL105285-01
Yes
Yale University
Yale University
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Indiana University
Principal Investigator: Henry Yaggi, MD,MPH Yale University
Principal Investigator: Dawn M Bravata, M.D. Indiana University School of Medicine
Yale University
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP