Specialized Pacing for Patients With Congenital Heart Disease

NCT03361189 | Terminated Phase 2 Results FDA Device

• 1 other identifier: 17-000932
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Congenital Heart Disease; Bradycardia Sinus

Keywords

Congenital heart disease; Pacemaker; Sinus node dysfunction

Outcome Measures

Primary Outcomes (2)

• 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

  3 months after the start of each intervention, a total of 6 months

• Heart Rate Response During a 48-hour Assessment Period

  Average heart rate as measured by Holter monitor for 48 hours during each intervention

  3 months after the start of each intervention, a total of 6 months

Secondary Outcomes (2)

• Average Oxygen Consumption During Each Intervention

  3 months after the start of each intervention, a total of 6 months

• Quality of Life as Assessed by SF-36

  3 months after the start of each intervention, a total of 6 months

Study Arms (2)

CLS-On

EXPERIMENTAL

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.

Device: Closed loop stimulation; Device: Standard rate response

CLS-Off

ACTIVE COMPARATOR

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.

Device: Closed loop stimulation; Device: Standard rate response

Interventions

Closed loop stimulation DEVICE

Closed loop stimulation is a physiologic, rate-adaptive pacing algorithm.

CLS-Off; CLS-On

Standard rate response DEVICE

Standard rate response is an algorithm to increase heartrate based on movement

CLS-Off; CLS-On

Eligibility Criteria

• Age: 14 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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%

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Biotronik, Inc.: collaborator

Study Sites (1)

University of California at Los Angeles

Los Angeles, California, 90095, United States

Location

Related Publications (10)

• 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.

  PMID: 23419655 BACKGROUND

• 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.

  PMID: 19822808 BACKGROUND

• 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.

  PMID: 17669080 BACKGROUND

• 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.

  PMID: 18272507 BACKGROUND

• 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.

  PMID: 18204100 BACKGROUND

• 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.

  PMID: 2462219 BACKGROUND

• 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.

  PMID: 11060870 BACKGROUND

• 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.

  PMID: 19889189 BACKGROUND

• 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.

  PMID: 14720151 BACKGROUND

• 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.

  PMID: 7074766 BACKGROUND

MeSH Terms

Conditions

Heart Defects, Congenital; Sick Sinus Syndrome

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Arrhythmia, Sinus; Arrhythmias, Cardiac; Heart Block; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Jeremy P. Moore
• Organization: UCLA

RGoldstein@mednet.ucla.edu

310-267-7667

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Model Details: 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.

Study Record Dates

• First Submitted: November 28, 2017
• First Posted: December 4, 2017
• Study Start: May 9, 2021
• Primary Completion: November 3, 2021
• Study Completion: November 3, 2021
• Last Updated: January 20, 2023
• Results First Posted: January 20, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)