Comparing Rate Response With CLS Versus Accelerometer ICD Settings in Heart Failure Patients With BIOTRONIK CRT-Ds (CLASS)

• ClinicalTrials.gov Identifier: NCT02693262
• Recruitment Status: Active, not recruiting
• First Posted: February 26, 2016
• Last Update Posted: May 12, 2020
• Sponsor: University of California, San Diego
• Collaborator: Biotronik, Inc.
• Information provided by (Responsible Party): Jonathan Hsu, University of California, San Diego

Study Description

Brief Summary:

Dr. Jonathan Hsu and Dr. Eric Adler are conducting a research study to find out more about how implantable cardiac defibrillator (ICD) settings can be adjusted to improve patient cardiovascular health and quality of life. Patients are being asked to participate in this study if they have a history of heart failure and have or are scheduled to be implanted with a BIOTRONIK ICD that is capable of closed loop stimulation (CLS). CLS is a device setting that works with the cardiovascular system to optimize their heart rate during physical activity. This study is comparing BIOTRONIK's CLS setting to a standard accelerometer setting, which also is able to adjust the heart rate by movement sensors, when necessary. This study has been initiated by Dr. Hsu and Dr. Adler and is financially supported by BIOTRONIK, Inc. There will be approximately 15 participants in this trial.

Condition or disease	Intervention/treatment	Phase
Heart Failure; ICD; Chronotropic Incompetence	Device: CLS Mode on Biotronik CRT-D; Device: Accelerometer Mode on Biotronik CRT-D	Not Applicable

Detailed Description:

This study is a prospective, randomized, single-blind crossover study intended to enroll patients who are implanted or are scheduled to be implanted with a Biotronik CLS and accelerometer capable CRT-D device. Patients will serve as their own control group with regard to modes of rate-adaptive pacing. Patients with a previously implanted Biotronik CRT-D device with CLS-capability will be recruited from health care institutions in San Diego and all dedicated functional testing will be performed at the University of California, San Diego (UCSD). The goal enrollment target for analysis will be 15 patients, with up to 20 patients enrolled to allow for withdrawals.

The purpose of this study is to evaluate whether changes to an implanted ICD can improve the functional status of patients with suspected chronotropic incompetence (CI). CI is a condition in which the heart rate is unable to adequately respond to meet the patient's physical demands, such as walking, climbing stairs, or doing household chores. CI is common in patients with cardiovascular disease, particularly in patients with heart failure. Common clinical management of patients with suspected CI is to activate an accelerometer setting in the cardiac resynchronization therapy with defibrillator (CRT-D) device. An accelerometer will adjust the heart rate to fit the physiological circumstances and needs of the patient based on patient movement only. BIOTRONIK is a company that has developed a novel technology included in the settings for CRT-D devices that offers CLS as an alternative to a standard accelerometer. CLS utilizes sensed electrical properties of the heart in order to assess what may be the best heart rate for both physical and mental demands. This study is designed to compare whether patients will benefit from CLS when compared with standard accelerometer technology.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Rate Response With CLS Versus Accelerometer and Effect on Both Subjective Symptoms and Objective Outcomes in a Heart Failure Population Implanted With Cardiac Resynchronization With Defibrillator Device: The CLASS Trial
• Study Start Date: July 2016
• Estimated Primary Completion Date: August 2020
• Estimated Study Completion Date: August 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: CLS Mode on Biotronik CRT-D; All 15 patients will be randomized to this group. Their device will be set in the CLS mode for 1 week.	Device: CLS Mode on Biotronik CRT-D; Setting changed and monitored. Quality of life evaluated through CPET, 6 Minute Walk Test, and Rand 36 Questionnaire.
Active Comparator: Accelerometer Mode on Biotronik CRT-D; All 15 patients will be randomized to this group. Their device will be set in the accelerometer rate responsive mode for 1 week.	Device: Accelerometer Mode on Biotronik CRT-D; Setting changed and monitored. Quality of life evaluated through CPET, 6 Minute Walk Test, and Rand 36 Questionnaire.

Outcome Measures

Primary Outcome Measures :

1. Cardiovascular health benefits from CLS versus accelerometer based rate responsive pacing [ Time Frame: three months ]
   To evaluate whether patients with left ventricular systolic heart failure implanted with CRT-D therapy who have evidence of chronotropic incompetence will benefit from CLS vs. accelerometer based rate responsive pacing. Objective measurements will be collected and analyzed from CPET and 6 Minute Walk Tests completed.
2. Quality of life benefits from CLS versus accelerometer based rate responsive pacing [ Time Frame: three months ]
   To evaluate whether patients with left ventricular systolic heart failure implanted with CRT-D therapy who have evidence of chronotropic incompetence will benefit from CLS vs. accelerometer based rate responsive pacing in terms of the patient's quality of life (via RAND-36 Health Outcomes Questionnaire)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Patients with a BIOTRONIK CRT-D device (capable of CLS and accelerometer rate responsive pacing)
• Patients at least 18 years old
• Patients who have plausible symptoms of CI based on previous monitoring and clinical symptoms

Exclusion Criteria:

• Pregnant patients
• Patients who are unwilling/unable to provide informed consent
• Patients who are unable to complete study related procedures
• Current persistent atrial fibrillation

Contacts and Locations

Locations

United States, California

Sulpizio Cardiovascular Center

La Jolla, California, United States, 92037

Sponsors and Collaborators

University of California, San Diego

Biotronik, Inc.

Investigators

• Principal Investigator: Jonathan Hsu, MD; University of California, San Diego

More Information

Publications:

Alt E. What is the ideal rate-adaptive sensor for patients with implantable cardioverter defibrillators: lessons from cardiac pacing. Am J Cardiol. 1999 Mar 11;83(5B):17D-23D. Review.

Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA 3rd, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Faxon DP, Halperin JL, Hiratzka LF, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura RA, Ornato JP, Page RL, Riegel B, Tarkington LG, Yancy CW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices); American Association for Thoracic Surgery; Society of Thoracic Surgeons. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. Circulation. 2008 May 27;117(21):e350-408. doi: 10.1161/CIRCUALTIONAHA.108.189742. Epub 2008 May 15. Erratum in: Circulation.2009 Aug 4; 120(5):e34-5.

Freedman RA, Hopper DL, Mah J, Hummel J, Wilkoff BL. Assessment of pacemaker chronotropic response: implementation of the Wilkoff mathematical model. Pacing Clin Electrophysiol. 2001 Dec;24(12):1748-54.

Maass AH, Buck S, Nieuwland W, Brügemann J, van Veldhuisen DJ, Van Gelder IC. Importance of heart rate during exercise for response to cardiac resynchronization therapy. J Cardiovasc Electrophysiol. 2009 Jul;20(7):773-80. doi: 10.1111/j.1540-8167.2008.01422.x. Epub 2009 Feb 2.

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.

Tse HF, Siu CW, Lee KL, Fan K, Chan HW, Tang MO, Tsang V, Lee SW, Lau CP. The incremental benefit of rate-adaptive pacing on exercise performance during cardiac resynchronization therapy. J Am Coll Cardiol. 2005 Dec 20;46(12):2292-7.

Keteyian SJ, Isaac D, Thadani U, Roy BA, Bensimhon DR, McKelvie R, Russell SD, Hellkamp AS, Kraus WE; HF-ACTION Investigators. Safety of symptom-limited cardiopulmonary exercise testing in patients with chronic heart failure due to severe left ventricular systolic dysfunction. Am Heart J. 2009 Oct;158(4 Suppl):S72-7. doi: 10.1016/j.ahj.2009.07.014.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hsu JC, Darden D, Alegre M, Birgersdotter-Green U, Feld GK, Hoffmayer KS, Han F, Krummen D, Raissi F, Ho G, Taub PR, Urey MA, Adler E. Effect of closed loop stimulation versus accelerometer on outcomes with cardiac resynchronization therapy: the CLASS trial. J Interv Card Electrophysiol. 2020 Aug 5. doi: 10.1007/s10840-020-00829-4. [Epub ahead of print]

• Responsible Party: Jonathan Hsu, Assistant Professor of Medicine, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT02693262
• Other Study ID Numbers: 151774
• First Posted: February 26, 2016
• Last Update Posted: May 12, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Jonathan Hsu, University of California, San Diego:

defibrillator; heart failure; ICD; CRT-D; cardiac resynchronization therapy; rate response; CLS; closed-loop stimulation; accelerometer; chronotropic incompetence

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases