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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Bradycardia

Intervention / Treatment
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* Device: Closed Loop Stimulation (CLS)
* Device: Standard Rate Adaptive (R) Technology
* Device: Non-rate adaptive (DDD) pacing


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Closed Loop Stimulation (CLS)<br>Pacemaker programmed with Closed Loop Stimulation rate adaptive technology for long-term follow-up data collection. | Device: Closed Loop Stimulation (CLS)<br>* 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.<br>* Other names: Cylos Pacemaker;|
| Active Comparator: Standard Rate Adaptive Technology (R)<br>Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term follow-up data collection. | Device: Standard Rate Adaptive (R) Technology<br>* 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.<br>* Other names: Cylos pacemaker;|
| Active Comparator: Non-rate adaptive pacing (DDD)<br>Pacemaker programmed with no rate adaption (DDD mode) for long-term follow-up data collection. | Device: Non-rate adaptive (DDD) pacing<br>* 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.<br>* Other names: Cylos pacemaker;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bradycardia, Sinus Node Dysfunction, Chronotropic incompetence, Pacemaker, Rate adaptive