Effectiveness of Pacemaker With Closed Loop Stimulation Compared to Pacemakers With and Without Standard Rate Response (CLEAR)

CLEAR: Cylos Pacemaker Responds With Physiologic Rate Changes During Daily Activities

This is a randomized, prospective, single-blinded, multi-center study involving approximately 1500 patients at 100 centers. The purpose of this study is to demonstrate the effectiveness of Closed Loop Stimulation (CLS) rate adaption technology over both standard rate responsive technology (R) and non-rate responsive mode (DDD) during activities of daily living (ADL).

Study Overview

• Status: Completed
• Conditions: Bradycardia
• Intervention / Treatment: Device: Closed Loop Stimulation (CLS); Device: Standard Rate Adaptive (R) Technology; Device: Non-rate adaptive (DDD) pacing

Detailed Description

All patients enrolled in the CLEAR study are implanted with a Cylos pacemaker with Closed Loop Stimulation (CLS) rate adaption technology. Any legally marketed pacing leads may be implanted with the Cylos family of pacemakers.

Prior to enrollment, patients provide written informed consent and are screened to ensure they are eligible to participate in the study. Patients enrolled in the study must have been implanted within 45 days prior to enrollment or are being considered for implant. Once enrolled and implanted with the Cylos pacemaker, the first 500 patients have 45 days to complete an ADL Testing visit. At the Activities of Daily Living (ADL) testing visit, each of the first 500 enrolled patients performs a 6-minute walk test, orthostatic test, and sweep test in three pacing modes, CLS (DDD-CLS or VVI-CLS), standard rate response (DDDR or VVIR) and non-rate responsive mode (DDD or VVI). The order of the pacing modes for testing is randomized in a 1:1:1 ratio. The study primarily analyzes the number of ADL repetitions performed during the 6-minute walk and sweep tests, pulse pressure during the orthostatic test, and secondarily analyzes heart rates during all three tests to compare CLS to both rate responsive and non-rate responsive pacing modes.

For all enrolled patients, the study collects additional data over a 12-month period. Patients are randomized and their pacemaker programmed to one of three pacing modes, CLS, R, or no-rate response in a 2:1:1 ratio, respectively. The patients are then followed for a period of 12 months after the ADL testing (first 500 enrolled patients) or enrollment (patients 501 through 1500). The study collects the following secondary measures to compare CLS to both rate responsive and non-rate responsive pacing modes: changes in 6-minute walk test distance, quality of life, mode reprogramming, atrial fibrillation (AF) burden, cardiac symptoms, and New York Heart Association (NYHA) classification.

• Study Type: Interventional
• Enrollment (Actual): 1491
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Albertville, Alabama, United States, 35951
      • Raymond Fernandez
    • Gadsden, Alabama, United States, 35901
      • Cardiology Associates-Gadsden
    • Gadsden, Alabama, United States, 35901
      • North Alabama Cardiology Center
    • Jasper, Alabama, United States, 35501
      • Richard Kim, MD
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Arizona Heart Institute
  • California
    • Anaheim, California, United States, 92804
      • N.R. Devaraj, M.D., Inc.
    • Benicia, California, United States, 94510
      • Family Doctor Medical Group
    • Downey, California, United States, 90240
      • Caremore Medical Group
    • Downey, California, United States, 90241
      • Multani Medical Group
    • Fairfield, California, United States, 94533
      • Solano Cardiology
    • Fremont, California, United States, 94538
      • Pacific Cardiology Associates
    • French Camp, California, United States, 95231
      • San Joaquin General Hospital
    • Jackson, California, United States, 95642
      • Kenny Charn, MD
    • Lakewood, California, United States, 90712
      • Kartik Thaker, MD
    • Mission Viejo, California, United States, 92691
      • Mission Internal Medical Group
    • Monterey, California, United States, 93940
      • Cardio-Pulmonary Associates
    • Murrieta, California, United States, 92562
      • St. Luke Cardiovascular Medical Group
    • Sacramento, California, United States, 95825
      • Sacramento Heart & Vascular
    • Torrance, California, United States, 90505
      • Torrance Memorial Medical Center
    • Torrance, California, United States, 90503
      • Emad Khaleeli, MD
    • Turlock, California, United States, 95382
      • Cardiology Consultants
    • Ventura, California, United States, 93003
      • Ventura Cardiology
    • Whittier, California, United States, 90603
      • Alireza Jafari, MD
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Boulder Medical Center
    • Boulder, Colorado, United States, 80301
      • Colorado Cardiovascular Center
    • Denver, Colorado, United States, 80218
      • Aurora Denver Cardiology Associates
    • Denver, Colorado, United States, 80210
      • Western Cardiology Associates
    • Englewood, Colorado, United States, 80113
      • Western Cardiology Associates
  • Delaware
    • Newark, Delaware, United States, 19713
      • Alfieri Cardiology
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Southern Heart Group
    • Melbourne, Florida, United States, 32901
      • Melbourne Internal Medicine Associates
    • New Smyrna Beach, Florida, United States, 32168
      • Complete Cardiology Care
    • Pensacola, Florida, United States, 32504
      • Cardiology Consultants, PA
    • Port St. John, Florida, United States, 32927
      • Space Coast Cardiology Consultants
    • Rockledge, Florida, United States, 32955
      • Brevard Cardiovascular Research Association
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Cardiology, PC
    • Augusta, Georgia, United States, 30904
      • Doris Tummillo, MD
    • Douglas, Georgia, United States, 31533
      • Collins Cardiology
    • Douglas, Georgia, United States, 31533
      • Douglas Medical Specialists
  • Illinois
    • Alton, Illinois, United States, 62002
      • St. Louis Cardiology Consultants - Alton
    • Centralia, Illinois, United States, 62801
      • Naeem Khan, MD
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Mount Vernon, Illinois, United States, 62864
      • Amr El-Shafei, MD
  • Kentucky
    • Louisville, Kentucky, United States, 40215
      • Bluegrass Cardiology
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02135
      • New England Cardiovascular Specialists
  • Michigan
    • Grand Rapids, Michigan, United States, 49525
      • West Michigan Cardiology
    • Lansing, Michigan, United States, 48910
      • Thorasic and Cardiovascular Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VA
  • Mississippi
    • Corinth, Mississippi, United States, 38834
      • Pidikiti Cardiology
    • Gulfport, Mississippi, United States, 39501
      • Coast Heart Institute
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • Midwest Health Professionals, P.C.
    • Crystal City, Missouri, United States, 63019
      • Cardiac Specialists of St. Lukes
    • Farmington, Missouri, United States, 63640
      • Chand Medical Office
    • Festus, Missouri, United States, 63028
      • Manzoor Tariq, MD
    • Liberty, Missouri, United States, 64068
      • Liberty Cardiovascular Specialists
    • Moberly, Missouri, United States, 65270
      • Heartland Medical Associates, LLC
    • Osage Beach, Missouri, United States, 65065
      • Lake Cardiovascular Institute, P.C.
    • St. Louis, Missouri, United States, 63122
      • Zia Ahmad, MD, FACC
    • St. Louis, Missouri, United States, 63128
      • Gateway Cardiology, PC
    • St. Louis, Missouri, United States, 63131
      • St. Louis Cardiology Center, P.C.
    • St. Louis, Missouri, United States, 63131
      • St. Louis Cardiovascular Center
    • St. Louis, Missouri, United States, 63136
      • Lalit Chouhan, MD
    • St. Louis, Missouri, United States, 63136
      • St. Louis Heart and Vascular, P.C.
  • New Jersey
    • West Orange, New Jersey, United States, 07052
      • Abbas Shehadeh, MD, FACC
  • New Mexico
    • Las Cruces, New Mexico, United States, 88011
      • White Sands Institute for Clinical Research
  • New York
    • Warsaw, New York, United States, 14569
      • Ohri Medical Group, P.C.
  • North Carolina
    • Concord, North Carolina, United States, 28025
      • Heart Group of the Carolinas
    • Elkin, North Carolina, United States, 28621
      • Carolina Heart Care
    • Gastonia, North Carolina, United States, 28054
      • Carolina Heart Specialists
    • Hickory, North Carolina, United States, 28602
      • Piedmont Cardiology
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
    • Fairview Park, Ohio, United States, 44126
      • Westside Cardiology Associates, Inc.
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic Cardiology
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Oklahoma Heart Institute
    • Tulsa, Oklahoma, United States, 74136
      • Bryan Lucenta, MD
  • Pennsylvania
    • Carbondale, Pennsylvania, United States, 18407
      • Lakshmi Mizin, M.D.
    • Sellersville, Pennsylvania, United States, 18960
      • Alderfer & Travis Associates
  • South Carolina
    • Aiken, South Carolina, United States, 29801
      • Carolina Heart and Vascular Center
    • Charleston, South Carolina, United States, 29403
      • Charleston Cardiology
    • Columbia, South Carolina, United States, 29204
      • South Carolina Heart Center
    • Florence, South Carolina, United States, 29505
      • Pee Dee Cardiology
    • Lancaster, South Carolina, United States, 29720
      • Carolina Heart Specialists
    • Rock Hill, South Carolina, United States, 29732
      • Carolina Cardiology Associates
  • Tennessee
    • Knoxville, Tennessee, United States, 37923
      • Heart Rhythm Specialists of East Tennessee
  • Texas
    • Amarillo, Texas, United States, 79106
      • Lone Star Arrhythmia and Heart Failure Center
    • Austin, Texas, United States, 78705
      • Austin Cardiac Clinic
    • Burleson, Texas, United States, 76028
      • Fort Worth Heart
    • Dallas, Texas, United States, 75216
      • Dallas VA Medical Center
    • El Paso, Texas, United States, 79902
      • Cardiology Care Consultants
    • Fort Worth, Texas, United States, 76104
      • Fort Worth Heart
    • San Angelo, Texas, United States, 76904
      • Cardiology Associates of West Texas
    • San Antonio, Texas, United States, 78229
      • Cardiac Electrophysiology Consultants of S. Texas
  • Utah
    • Salt Lake City, Utah, United States, 84123
      • Wasatch Cardiology Consultants, PC
  • Virginia
    • Richmond, Virginia, United States, 23249
      • McGuire VA Medical Center
    • Richmond, Virginia, United States, 23225
      • Cardiovascular Associates of Virginia
  • Washington
    • Burien, Washington, United States, 98166
      • Daniel Gottlieb
  • Wisconsin
    • Waukesha, Wisconsin, United States, 53188
      • Waukesha Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Implanted within the last 45 days or being considered for implant with a BIOTRONIK pacemaker utilizing CLS rate adaptation technology (currently the Cylos family of pacemakers).
• Ability to give written informed consent
• Geographically stable and able to return for regular follow-ups for 12 months after ADL testing
• At least 18 years old

Exclusion Criteria:

• Patients physically limited and unable to perform all or parts of the ADL testing
• Currently enrolled in any other clinical study
• Patients with medical reasons that preclude regular participation in the follow-ups

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Closed Loop Stimulation (CLS); Pacemaker programmed with Closed Loop Stimulation rate adaptive technology for long-term follow-up data collection.	Device: Closed Loop Stimulation (CLS); Comparison of different pacing modes available on the Cylos pacemaker device. In this intervention group, subjects were programmed to the Closed Loop Stimulation (DDD-CLS or VVI-CLS) pacing mode for the long-term follow-up portion of this study.; Other Names: Cylos Pacemaker
Active Comparator: Standard Rate Adaptive Technology (R); Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term follow-up data collection.	Device: Standard Rate Adaptive (R) Technology; Comparison of different pacing modes available on the Cylos pacemaker device. In this intervention group, subjects were programmed to the standard are adaptive pacing mode (DDDR or VVIR) for the long-term follow-up portion of this study.; Other Names: Cylos pacemaker
Active Comparator: Non-rate adaptive pacing (DDD); Pacemaker programmed with no rate adaption (DDD mode) for long-term follow-up data collection.	Device: Non-rate adaptive (DDD) pacing; Comparison of different pacing modes available on the Cylos pacemaker device. In this intervention group, subjects were programmed to the non-rate adaptive pacing mode (DDD or VVI) for the long-term follow-up portion of this study.; Other Names: Cylos pacemaker

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance of Activities of Daily Living Tests (6-minute Walk and Sweep)	Six-minute walk test and sweep test results for subjects completing tests in all three pacing modes and requiring at least 80% pacing during both tests in the CLS and R pacing modes. The mean composite of repetitions (six minute walk plus sweep) are presented.	within 45 days of enrollment
Pulse Pressure During Activities of Daily Living Tests (Orthostatic Test)	Patients completing the orthostatic test in all three pacing modes and that had at least 80% pacing during the test in the CLS and R pacing modes are included in the analysis. The mean pulse pressure is provided.	within 45 days of enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Quality of Life	Change in Quality of life (QOL) score was determined from baseline to the 12 month follow-up visit. The QOL utilized the physical functioning scale of the SF-36 v2, in which a higher score indicates a better health perception. Best possible score was 57.03 while the worst possible score was 14.94.	baseline and 12 months
Mode Reprogramming	Number of subjects with device reprogramming from dual (atrial and ventricular pacing) to single chamber (ventricular pacing only) or from single (ventricular pacing only) to dual chamber (atrial and ventricular pacing) during the 12 month follow-up.	12 months
Atrial Fibrillation (AF) Burden	AF burden was measured at 12 months as the percentage of total atrial beats that are at or above 160 bpm.	12 months
Cardiac Symptoms	Number of subjects exhibiting each cardiac symptom was determined at the 12 month follow-up visit.	12 months
Change in New York Heart Association (NYHA) Class	Number of subjects with improved, no change, or worsened NYHA classification at the 12-month visit, as compared to baseline. NYHA classifications (I to IV) are used to assess the various stages of heart failure, with Class I relating to mild heart failure and Class IV relating to severe heart failure.	baseline and 12 months
Change in 6-minute Walk Test Distance	Change in number of 10 foot repetitions between baseline and 12-month visit were examined.	baseline and 12 months

Collaborators and Investigators

• Sponsor: Biotronik, Inc.
• Investigators: Principal Investigator: Freddy Abi-Samra, MD, Ochsner Health System

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: July 21, 2006
• First Submitted That Met QC Criteria: July 24, 2006
• First Posted (Estimate): July 25, 2006

Study Record Updates

• Last Update Posted (Estimate): December 20, 2012
• Last Update Submitted That Met QC Criteria: December 18, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Pacemaker; Sinus Node Dysfunction; Bradycardia; Chronotropic incompetence; Rate adaptive
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Bradycardia
• Other Study ID Numbers: 20060536