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Specialized Pacing for Patients With Congenital Heart Disease

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ClinicalTrials.gov Identifier: NCT03361189
Recruitment Status : Not yet recruiting
First Posted : December 4, 2017
Last Update Posted : December 4, 2017
Sponsor:
Collaborator:
Biotronik, Inc.
Information provided by (Responsible Party):
Jeremy P. Moore, MD, University of California, Los Angeles

November 28, 2017
December 4, 2017
December 4, 2017
February 1, 2018
February 1, 2023   (Final data collection date for primary outcome measure)
Heart rate response [ Time Frame: 3 months ]
Heart rate in response to mental stress and autonomic input will be asssessed
Same as current
No Changes Posted
  • Oxygen uptake [ Time Frame: 3 months ]
    Oxygen uptake will be determined by cardiopulmonary gas exchange
  • Quality of life [ Time Frame: 3 months ]
    Quality of life will be assessed by SF-36 questionnaire
Same as current
Not Provided
Not Provided
 
Specialized Pacing for Patients With Congenital Heart Disease
A Randomized Trial of Closed Loop Stimulation After Epicardial Pacemaker Implantation for Congenital Heart Disease
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.

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.

The Specific Aims of this protocol are:

Primary Aim: To determine the performance of CLS for CHD patients after both transvenous and epicardial pacemaker implantation

Hypothesis: CLS after either pacemaker implantation strategy will result in equivalent improvements in autonomic control of chronotropic response as compared to standard sensor based rate modulation

Primary outcome: Objective change in autonomic modulation of heart rate while randomized to CLS pacing with mental stress and ANSAR testing

Secondary outcomes: Increase in aerobic capacity, non-sedentary behavior, and quality of life while randomized to CLS pacing

This will be a single-blind (blinded subjects) randomized cross-over study, in which each patient will receive treatment A (CLS-on or CLS-off) for 3 months followed by treatment B (CLS-off or CLS-on).

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%

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.

6.0 Study Procedures

All patients enrolled in the study will undergo the following baseline assessment and data collection:

  • Demographics (age, gender, race/ethnicity)
  • Review of data confirming the presence of sinus node dysfunction with chronotropic incompetence (prior exercise stress test and/or Holter monitor results)
  • Review of clinical history, including age at diagnosis, congenital diagnosis, surgical history, and cardiac device implant procedure
  • Antiarrhythmic drugs prescribed and the respective dosages
  • Prior ECG and echocardiography and advanced imaging reports

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. During the testing period, subjects will be tracked with the implanted device accelerometer to quantify physical activity. At 3 months, all subjects will undergo testing as noted below.

  • 24 hour Holter monitoring with spectral analysis
  • Cycle-ergometer stress with cardiopulmonary gas exchange analysis
  • Free form activities with cardiopulmonary gas exchange analysis (staircase walking, sweeping, suitcase lifting with right and left arms, etc.)
  • ANSAR testing (hand grip, Valsalva, deep breathing, and orthostatic challenge)
  • Mental stress test with continuous electrocardiographic recording
  • Quality of life questionnaire (SF-36/Somerville index)

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 as described above. At the conclusion of the study, patients will be asked which pacing mode is preferred.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention 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: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
  • Congenital Heart Disease
  • Bradycardia Sinus
Device: Closed loop stimulation
Closed loop stimulation is a physiologic, rate-adaptive pacing algorithm.
  • Experimental: CLS-On
    Subjects in this arm will programmed to CLS-on to received closed loop stimulation-based pacing.
    Intervention: Device: Closed loop stimulation
  • No Intervention: CLS-Off
    Subjects in this arm, will be placed in a standard pacing mode (i.e. AAIR or DDDR).

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
18
August 1, 2023
February 1, 2023   (Final data collection date for primary outcome measure)

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%
Sexes Eligible for Study: All
14 Years to 65 Years   (Child, Adult)
No
Contact: Jeremy P Moore, MD, MS 310-267-7600 jpmoore@mednet.ucla.edu
Contact: Kevin M Shannon, MD 310-267-7600 kshannon@mednet.ucla.edu
United States
 
 
NCT03361189
17-000932
No
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No
Plan to Share IPD: No
Jeremy P. Moore, MD, University of California, Los Angeles
University of California, Los Angeles
Biotronik, Inc.
Not Provided
University of California, Los Angeles
November 2017

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