Specialized Pacing for Patients With Congenital Heart Disease
Primary Purpose
Congenital Heart Disease, Bradycardia Sinus
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Closed loop stimulation
Standard rate response
Sponsored by
About this trial
This is an interventional treatment trial for Congenital Heart Disease focused on measuring Congenital heart disease, Pacemaker, Sinus node dysfunction
Eligibility Criteria
Inclusion Criteria:
Congenital heart disease
• Simple, moderate, or complex congenital heart disease
- Adolescent or adult age group (age >14 and <65 years)
Significant sinus node dysfunction
- Atrial pacing percentage >70%11
- Intrinsic dysfunction resulting from congenital lesion or cardiac surgery
- Secondary sinus node dysfunction due to antiarrhythmic drug therapy
- Existing, fully functional pacemaker or ICD with CLS capability
- Epicardial or transvenous route of pacemaker implantation
Exclusion Criteria:
- Unable to complete cardiopulmonary exercise testing (CPET)
- Contraindication to CPET
- Decreased mental capacity or known psychiatric disorder
- Congestive heart failure, NYHA cass IV
- Total atrial tachyarrhythmia burden >20%
Sites / Locations
- University of California at Los Angeles
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
CLS-On
CLS-Off
Arm Description
Subjects in this arm will be programmed to CLS-on to received closed loop stimulation-based pacing for 3 months, followed by a standard rate response for 3 months.
Subjects in this arm, will be placed in a standard rate response for 3 months, followed by CLS-on to received closed loop stimulation-based pacing for 3 months.
Outcomes
Primary Outcome Measures
Number of Participants With Blunted or Unchanged Effect of Mental Stress on Heart Rate
Heart rate in response to mental stress during each intervention; a math test was performed during autonomic testing
Heart Rate Response During a 48-hour Assessment Period
Average heart rate as measured by Holter monitor for 48 hours during each intervention
Secondary Outcome Measures
Average Oxygen Consumption During Each Intervention
Oxygen uptake as determined by cardiopulmonary gas exchange during a stress test under 4 conditions:
Sitting/standing 60 seconds Kettlebell walking 110 seconds Stairs 176 seconds Sweeping 62 seconds
Quality of Life as Assessed by SF-36
Quality of life as assessed by SF-36 questionnaire following each period of intervetion. SF- 36 investigates the standard of quality of life through a general health assessment and not specific to a particular disease, age or treatment group. It is a 36-item questionnaire measuring 8 domains [physical functioning, role limitations due to physical health (role physical), bodily pain, general health, energy, social functioning, role limitations due to emotional health (role emotional), and emotional wellbeing]. Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status.
Full Information
NCT ID
NCT03361189
First Posted
November 28, 2017
Last Updated
December 22, 2022
Sponsor
University of California, Los Angeles
Collaborators
Biotronik, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03361189
Brief Title
Specialized Pacing for Patients With Congenital Heart Disease
Official Title
A Randomized Trial of Closed Loop Stimulation After Epicardial Pacemaker Implantation for Congenital Heart Disease
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Terminated
Why Stopped
Insufficient recruitment
Study Start Date
May 9, 2021 (Actual)
Primary Completion Date
November 3, 2021 (Actual)
Study Completion Date
November 3, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Los Angeles
Collaborators
Biotronik, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The closed-loop stimulation (CLS) algorithm is a novel sensor-based technology that relies on the change in myocardial systolic impedance for modulation of the heart rate during physical and emotional stress.3 The pacing algorithm has been shown to be highly effective for a wide range of clinical scenarios. Despite the fact that congenital heart disease (CHD) patients are likely to derive significant benefit in terms of functional ability and aerobic capacity using this novel technology, the CLS system has not been adequately studied in this population. As many CHD patients also undergo epicardial placement of pacing systems at the time of concomitant cardiac surgery, CLS has been less often utilized in this population given almost no data in the setting of surgical electrode placement. The present study intends to examine the benefits of the CLS algorithm in the CHD population, employing the use of epicardial pacemaker systems in the study protocol.
Detailed Description
Sinus node dysfunction is highly prevalent among patients with congenital heart disease, manifesting as resting bradycardia or chronotropic incompetence. As children and adults with congenital heart disease are now expected to have increasing life-expectancy; with well over 1 million adult patients currently living in North America,1 issues such as mental health, acquired comorbidities and their impact on overall cardiovascular health have assumed increased scrutiny.
It is now understood that objective measures of aerobic capacity, such as peak VO2, peak VE/VCO2, and heart rate reserve predict all-cause mortality for adult patients with congenital heart disease. As the chronotropic response during exercise is a key determinant of aerobic capacity, improvement in sensor-based technology for heart rate support is expected to have a significant impact on functional capacity and longevity in this population. Some forms of congenital heart disease, such as single ventricle physiology after the Fontan population are especially likely to benefit, as cardiac output is determined almost exclusively by heart rate during exertion due to limited ability to augment cardiac stroke volume.2
It is also becoming increasingly clear that sedentary behaviors are highly relevant to overall cardiovascular health in the general adult population. Adult patients with congenital heart disease are at especially high risk for sedentary behavior as a result of 1) chronic restriction for physical activities based on ill-founded medical advice, 2) chronotropic incompetence resulting from prior surgical palliations and hemodynamic stressors, and 3) overestimation of physical activity.
5.0 Enrollment/Randomization
Patient Enrollment: The treating physician will identify potential subjects with a previously implanted pacemaker and present a brief overview of the study; if the subject is interested, the study will be described in detail. Informed consent will be obtained by the investigator after discussing the study, including the voluntary nature of participation and notification the subject can withdraw at any time. Ample time for questions and answers will be allowed. The investigator will give the subject and his/her legal guardian the opportunity to take the consent home to think about it more, with the option to call or meet with the investigator to ask additional questions. If the subject and/or his/her parent/legal guardian agree to participate, the investigator will ask them to sign a written, informed consent and assent. A copy of the assent and consent will be given to the subject and/or his/her parent/legal guardian.
Randomization Procedure: This will be a single-blind placebo-controlled randomized crossover study with 2 treatments: CLS-on versus CLS-off (accelerometer only). Each enrolled patient will receive both treatments for 3 months. The order of treatments will be randomized 1:1.
Randomization
There will be a 50:50 randomization, with half the subjects randomized to CLS-on then CLS-off, and half randomized to CLS-off then CLS-on.
Subjects previously receiving rate-responsive pacing with CLS that are randomly selected to CLS-on will continue with the identical programmed parameters. For subjects not previously receiving rate-responsive pacing with CLS that are randomly selected to CLS-on nominal programming will be utilized with a base rate of 60 beats per minute.
Subjects will then initiate treatment A (CLS-on or CLS-off) in a blinded fashion. At 3 months, subjects will undergo testing.
After 3 months of treatment A, subjects will be reprogrammed to treatment B. Tracking of physical activity with the device accelerometer will continue during this period. After 3 months of treatment B, repeat testing will be repeated.
Patients will be followed during both treatment phases per usual clinical routine. Patients who experience significant symptoms (extreme fatigue, debilitating palpitations, or other clinically relevant symptoms) will be evaluated by their treating physician. Subjects that have any adverse events during treatment A will discontinue treatment A and immediately crossover to treatment B. Subjects with events during treatment B will be removed from the study and unblinded. Further treatment will be determined by the treating physician.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Heart Disease, Bradycardia Sinus
Keywords
Congenital heart disease, Pacemaker, Sinus node dysfunction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Crossover Assignment
Model Description
Patient Enrollment: The treating physician will identify potential subjects with a previously implanted pacemaker and present a brief overview of the study. Informed consent will be obtained by the investigator after discussing the study, including the voluntary nature of participation and notification the subject can withdraw at any time. The investigator will give the subject and his/her legal guardian the opportunity to take the consent home to think about it more, with the option to call or meet with the investigator to ask additional questions. If the subject and/or his/her parent/legal guardian agree to participate, the investigator will ask them to sign a written, informed consent and assent.
Randomization Procedure: This will be a single-blind placebo-controlled randomized crossover study with 2 treatments: CLS-on versus CLS-off (accelerometer only). Each enrolled patient will receive both treatments for 3 months. The order of treatments will be randomized 1:1.
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CLS-On
Arm Type
Experimental
Arm Description
Subjects in this arm will be programmed to CLS-on to received closed loop stimulation-based pacing for 3 months, followed by a standard rate response for 3 months.
Arm Title
CLS-Off
Arm Type
Active Comparator
Arm Description
Subjects in this arm, will be placed in a standard rate response for 3 months, followed by CLS-on to received closed loop stimulation-based pacing for 3 months.
Intervention Type
Device
Intervention Name(s)
Closed loop stimulation
Intervention Description
Closed loop stimulation is a physiologic, rate-adaptive pacing algorithm.
Intervention Type
Device
Intervention Name(s)
Standard rate response
Intervention Description
Standard rate response is an algorithm to increase heartrate based on movement
Primary Outcome Measure Information:
Title
Number of Participants With Blunted or Unchanged Effect of Mental Stress on Heart Rate
Description
Heart rate in response to mental stress during each intervention; a math test was performed during autonomic testing
Time Frame
3 months after the start of each intervention, a total of 6 months
Title
Heart Rate Response During a 48-hour Assessment Period
Description
Average heart rate as measured by Holter monitor for 48 hours during each intervention
Time Frame
3 months after the start of each intervention, a total of 6 months
Secondary Outcome Measure Information:
Title
Average Oxygen Consumption During Each Intervention
Description
Oxygen uptake as determined by cardiopulmonary gas exchange during a stress test under 4 conditions:
Sitting/standing 60 seconds Kettlebell walking 110 seconds Stairs 176 seconds Sweeping 62 seconds
Time Frame
3 months after the start of each intervention, a total of 6 months
Title
Quality of Life as Assessed by SF-36
Description
Quality of life as assessed by SF-36 questionnaire following each period of intervetion. SF- 36 investigates the standard of quality of life through a general health assessment and not specific to a particular disease, age or treatment group. It is a 36-item questionnaire measuring 8 domains [physical functioning, role limitations due to physical health (role physical), bodily pain, general health, energy, social functioning, role limitations due to emotional health (role emotional), and emotional wellbeing]. Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status.
Time Frame
3 months after the start of each intervention, a total of 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Congenital heart disease
• Simple, moderate, or complex congenital heart disease
Adolescent or adult age group (age >14 and <65 years)
Significant sinus node dysfunction
Atrial pacing percentage >70%11
Intrinsic dysfunction resulting from congenital lesion or cardiac surgery
Secondary sinus node dysfunction due to antiarrhythmic drug therapy
Existing, fully functional pacemaker or ICD with CLS capability
Epicardial or transvenous route of pacemaker implantation
Exclusion Criteria:
Unable to complete cardiopulmonary exercise testing (CPET)
Contraindication to CPET
Decreased mental capacity or known psychiatric disorder
Congestive heart failure, NYHA cass IV
Total atrial tachyarrhythmia burden >20%
Facility Information:
Facility Name
University of California at Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
23419655
Citation
Abi-Samra FM, Singh N, Rosin BL, Dwyer JV, Miller CD; CLEAR Study Investigators. Effect of rate-adaptive pacing on performance and physiological parameters during activities of daily living in the elderly: results from the CLEAR (Cylos Responds with Physiologic Rate Changes during Daily Activities) study. Europace. 2013 Jun;15(6):849-56. doi: 10.1093/europace/eus425. Epub 2013 Feb 17.
Results Reference
background
PubMed Identifier
19822808
Citation
Bouchardy J, Therrien J, Pilote L, Ionescu-Ittu R, Martucci G, Bottega N, Marelli AJ. Atrial arrhythmias in adults with congenital heart disease. Circulation. 2009 Oct 27;120(17):1679-86. doi: 10.1161/CIRCULATIONAHA.109.866319. Epub 2009 Oct 12.
Results Reference
background
PubMed Identifier
17669080
Citation
Chandiramani S, Cohorn LC, Chandiramani S. Heart rate changes during acute mental stress with closed loop stimulation: report on two single-blinded, pacemaker studies. Pacing Clin Electrophysiol. 2007 Aug;30(8):976-84. doi: 10.1111/j.1540-8159.2007.00795.x.
Results Reference
background
PubMed Identifier
18272507
Citation
Coenen M, Malinowski K, Spitzer W, Schuchert A, Schmitz D, Anelli-Monti M, Maier SK, Estlinbaum W, Bauer A, Muehling H, Kalscheur F, Puerner K, Boergel J, Osswald S. Closed loop stimulation and accelerometer-based rate adaptation: results of the PROVIDE study. Europace. 2008 Mar;10(3):327-33. doi: 10.1093/europace/eun024. Epub 2008 Feb 13.
Results Reference
background
PubMed Identifier
18204100
Citation
Di Pino A, Agati S, Bianca I. Efficacy of closed-loop stimulation with epicardial leads in an infant with congenital atrioventricular block. Europace. 2008 Mar;10(3):334-5. doi: 10.1093/europace/eum299. Epub 2008 Jan 20.
Results Reference
background
PubMed Identifier
2462219
Citation
Hedman A, Nordlander R. Changes in QT and Q-aT intervals induced by mental and physical stress with fixed rate and atrial triggered ventricular inhibited cardiac pacing. Pacing Clin Electrophysiol. 1988 Oct;11(10):1426-31. doi: 10.1111/j.1540-8159.1988.tb04991.x.
Results Reference
background
PubMed Identifier
11060870
Citation
Osswald S, Cron T, Gradel C, Hilti P, Lippert M, Strobel J, Schaldach M, Buser P, Pfisterer M. Closed-loop stimulation using intracardiac impedance as a sensor principle: correlation of right ventricular dP/dtmax and intracardiac impedance during dobutamine stress test. Pacing Clin Electrophysiol. 2000 Oct;23(10 Pt 1):1502-8. doi: 10.1046/j.1460-9592.2000.01502.x.
Results Reference
background
PubMed Identifier
19889189
Citation
Quaglione R, Calcagnini G, Censi F, Piccirilli F, Iannucci L, Raveggi M, Biancalana G, Bartolini P. Autonomic function during closed loop stimulation and fixed rate pacing: heart rate variability analysis from 24-hour Holter recordings. Pacing Clin Electrophysiol. 2010 Mar;33(3):337-42. doi: 10.1111/j.1540-8159.2009.02615.x. Epub 2009 Nov 4.
Results Reference
background
PubMed Identifier
14720151
Citation
Santini M, Ricci R, Pignalberi C, Biancalana G, Censi F, Calcagnini G, Bartolini P, Barbaro V. Effect of autonomic stressors on rate control in pacemakers using ventricular impedance signal. Pacing Clin Electrophysiol. 2004 Jan;27(1):24-32. doi: 10.1111/j.1540-8159.2004.00381.x.
Results Reference
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PubMed Identifier
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Citation
Shachar GB, Fuhrman BP, Wang Y, Lucas RV Jr, Lock JE. Rest and exercise hemodynamics after the Fontan procedure. Circulation. 1982 Jun;65(6):1043-8. doi: 10.1161/01.cir.65.6.1043.
Results Reference
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Specialized Pacing for Patients With Congenital Heart Disease
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