Ignite Creation Date:
2024-05-06 @ 8:19 PM
Last Modification Date:
2024-10-26 @ 3:25 PM
Study NCT ID:
NCT06332391
Status:
RECRUITING
Last Update Posted:
2024-05-07
First Post:
2023-11-27
Brief Title:
Paced Heart Rate Acceleration for Cardiac Conditioning
Sponsor:
Denice Hodgson-Zingman MD
Organization:
University of Iowa
Study Overview
Official Title:
A New Pacing Approach for Cardiac Conditioning and Enhanced Cardioprotection
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HeartExcel
Brief Summary:
A clinical trial of exercise-similar heart rate acceleration delivered via cardiac pacing vs sham intervention in subjects at rest will be performed The study population comprises subjects with guideline-directed medically managed severe left ventricular dysfunction due to ischemic or non-ischemic cardiomyopathy and an existing implantable cardioverter defibrillator or biventricular implantable cardioverter defibrillator The purpose of the study is to understand how the heart rate pattern of exercise contributes to the considerable cardiac conditioning effects of exercise and estimate whether the pacing approach may have translational clinical applicability Fifty-two subjects will be randomized single-blinded to either the pacing intervention or a sham intervention which they will receive once daily 3 daysweek for 6 weeks Baseline symptoms and clinical test results will be compared to the same measures at 2 weeks 4 weeks and 6 weeks of interventionsham and at 3 months and one-year post-intervention The primary endpoint will be the change in left ventricular ejection fraction from baseline in intervention vs sham groups mixed effects linear regression with time and treatment arm as fixed effects and pre-specified covariates of sex and cardiomyopathy type as random effects Secondary endpoints will include changes in quality of life 6-minute walk distance cardiopulmonary exercise test CPET measures daily activity and major adverse cardiac events MACE at 3 and 12 months between pacing and sham groups A dose-response analysis of outcomes at 2 4 and 6 weeks of the intervention vs sham compared with baseline will be performed
Detailed Description:
Subjects and protocol This is a phase II randomized controlled prospective clinical trial in subjects with systolic heart failure It is designed to assess the effect on symptoms functional structural and medical outcomes in response to an atrial paced reproduction of the heart rate exercise pattern delivered regularly over a 6-week period A single center University of Iowa will execute the interventionsham and subject testing A separate center Cleveland Clinic will perform statistical analysis of deidentified data Fifty-two subjects will be randomized 11 by computer generated code to either the intervention pacing arm or the sham arm The subject but not researcher will be blinded to randomization status single-blind Analysis of data will be performed in a blinded fashion Within 2 weeks prior to initiation of pacing vs sham interventions baseline testing will be performed including collection and storage of plasma testing for blood urea nitrogen BUN creatinine N-terminal pro-b-type natriuretic peptide NT-proBNP echocardiographic left ventricular LV dimensions left ventricular ejection fraction LVEF and quality of lifesymptoms by both the Minnesota Living with Heart Failure MLHF and the Kansas City Cardiomyopathy Questionnaire KCCQ designed for assessment of symptoms over 1 month and 2 week windows respectively distance on 6-minute walk 1 week of pacing device accelerometer-derived activity measures wearable activity monitor measures and cardiopulmonary exercise test CPET for determination of metabolic equivalents METs maximum oxygen consumption VO2max and anaerobic threshold AT estimated noninvasively using the rapid incremental exercise test In addition starting 1 week prior and continuing through 1 month after the pacing vs sham intervention each subject will be provided a wearable activity monitor and their daily activity analyzed as a cofactor At the end of 2 4 and 6 weeks of pacingsham as well as 3 and 12 months after the intervention the same outcome measures as at baseline will be collected as well as major adverse cardiovascular events MACE weight medications and arrhythmias recorded on the subjects implantable cardioverter defibrillator ICD or biventricular ICD BiVICD At the end of the pacesham period subject blinding will be assessed by asking subjects if they believe they were in pace or sham group Collected plasma will be saved for metabolomic testing in year 5 to correlate with findings in mouse models Outcomes All tests result analyses will be done by 2 independent clinicians qualified in specific areas blinded to the randomization A reviewer who analyzes a testing parameter will analyze the same parameter for all subjects Variability between reviewers will be analyzed The primary endpoint will be change in left ventricular ejection fraction LVEF from baseline Secondary endpoints will include quality of life QOL by MLHF score 6-min walk distance CPET including VO2max metabolic equivalents METs achieved peak power output total exercise time daily activity change from baseline and MACE at 3 and 12 months between pacing and sham groups A dose-response analysis of outcomes at 2 4 and 6 weeks of the intervention vs sham compared with baseline will be performed Durability analysis of response at 3 and 12 months will be performed
The data from all subjects completing at least one pacing vs sham session will undergo analysis for measures of tolerability symptoms maximum achieved pacing rate appearance of arrhythmias changes in vital signs and bioimpedance cardiac output with respect to age sex degree type of cardiomyopathy ischemic vs non-ischemic left ventricular function NT-proBNP NHYA class baseline oxygen consumption VO2 baseline exertional tolerance baseline physical activity level as assessed by the ICD of BiVICD accelerometer and wearable activity watch autonomic function as defined by heart rate variability derived from electrocardiogram ECG and stored ICD or BiVICD data Hospitalizations deaths or other adverse outcomes will similarly be analyzed with respect to baseline data and procedural data such as maximum achieved pacing rate
For those subjects completing the interventionsham and follow up visits the primary endpoint of change in left ventricular ejection fraction will be analyzed Secondary endpoints will include changes in functional capacity particularly 6-minute walk and quality of life indicators as well as MACE with respect to the above study variables
Descriptive statistics will be used to summarize participant demographic and clinical characteristics at baseline Categorical variables will be compared using Chi squared tests For continuous variables to relax the strict requirement of normality non-parametric methods for unadjusted comparison will be used Wilcoxon rank-sum test also known as the Mann-Whitney two-sample statistic for comparison of two independent samples Wilcoxon matched pairs signed-rank test will be used for paired comparisons For the primary endpoint analysis a mixed-effects linear regression model will be used to compare the two study arms on the primary outcome of LVEF with time 2 4 and 6 wks and treatment arm intervention vs sham included as fixed effects and pre-specified covariates of sex binary malefemale and cardiomyopathy type binary ischemicnon-ischemic as random effects Both stratified randomization by sex and cardiomyopathy type as well as adjustment for these covariates in the analysis will be performed Although often only one or the other technique is sufficient both are performed here given the well-known confounding effects of sex and cardiomyopathy types in heart failure trials and a desire to be highly rigorous in this regard An intercept for time of treatment or sham 2 4 6 wks will be included The significance criteria for the model coefficient corresponding to treatment will be 025 with a one-sided 975 confidence interval Analyses will be conducted on an intention-to-treat basis Estimates and confidence intervals of effect sizes and standard deviation of outcome measures will be presented Pre-specified subgroup analyses will probe for treatment effect heterogeneity in outcomes based on sex and ischemic cardiomyopathy vs nonischemic cardiomyopathy Secondary endpoints will be analyzed in a fashion similar to the primary endpoint analysis Due to the controlled environment missing data are expected to be very rare If such exists patterns will be evaluated and multiple imputation performed
The data from all subjects completing at least one pacing vs sham session will undergo analysis for measures of tolerability symptoms maximum achieved pacing rate appearance of arrhythmias changes in vital signs and bioimpedance cardiac output with respect to age sex degree type of cardiomyopathy ischemic vs non-ischemic left ventricular function NT-proBNP NHYA class baseline oxygen consumption VO2 baseline exertional tolerance baseline physical activity level as assessed by the ICD of BiVICD accelerometer and wearable activity watch autonomic function as defined by heart rate variability derived from electrocardiogram ECG and stored ICD or BiVICD data Hospitalizations deaths or other adverse outcomes will similarly be analyzed with respect to baseline data and procedural data such as maximum achieved pacing rate
For those subjects completing the interventionsham and follow up visits the primary endpoint of change in left ventricular ejection fraction will be analyzed Secondary endpoints will include changes in functional capacity particularly 6-minute walk and quality of life indicators as well as MACE with respect to the above study variables
Descriptive statistics will be used to summarize participant demographic and clinical characteristics at baseline Categorical variables will be compared using Chi squared tests For continuous variables to relax the strict requirement of normality non-parametric methods for unadjusted comparison will be used Wilcoxon rank-sum test also known as the Mann-Whitney two-sample statistic for comparison of two independent samples Wilcoxon matched pairs signed-rank test will be used for paired comparisons For the primary endpoint analysis a mixed-effects linear regression model will be used to compare the two study arms on the primary outcome of LVEF with time 2 4 and 6 wks and treatment arm intervention vs sham included as fixed effects and pre-specified covariates of sex binary malefemale and cardiomyopathy type binary ischemicnon-ischemic as random effects Both stratified randomization by sex and cardiomyopathy type as well as adjustment for these covariates in the analysis will be performed Although often only one or the other technique is sufficient both are performed here given the well-known confounding effects of sex and cardiomyopathy types in heart failure trials and a desire to be highly rigorous in this regard An intercept for time of treatment or sham 2 4 6 wks will be included The significance criteria for the model coefficient corresponding to treatment will be 025 with a one-sided 975 confidence interval Analyses will be conducted on an intention-to-treat basis Estimates and confidence intervals of effect sizes and standard deviation of outcome measures will be presented Pre-specified subgroup analyses will probe for treatment effect heterogeneity in outcomes based on sex and ischemic cardiomyopathy vs nonischemic cardiomyopathy Secondary endpoints will be analyzed in a fashion similar to the primary endpoint analysis Due to the controlled environment missing data are expected to be very rare If such exists patterns will be evaluated and multiple imputation performed
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01HL168752 | NIH | None | httpsreporternihgovquickSearchR01HL168752 |