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

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ClinicalTrials.gov Identifier: NCT00355797
Recruitment Status : Completed
First Posted : July 25, 2006
Results First Posted : June 27, 2011
Last Update Posted : December 20, 2012
Sponsor:
Information provided by (Responsible Party):
Biotronik, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Treatment
Condition Bradycardia
Interventions Device: Closed Loop Stimulation (CLS)
Device: Standard Rate Adaptive (R) Technology
Device: Non-rate adaptive (DDD) pacing
Enrollment 1491
Recruitment Details  
Pre-assignment Details  
Arm/Group Title CLS Rate Adaptive Pacing Standard Rate Adaptive Pacing No Rate Adaptive Pacing
Hide Arm/Group Description Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up. Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up. Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Period Title: Overall Study
Started 741 369 381
Completed 501 221 239
Not Completed 240 148 142
Arm/Group Title CLS Rate Adaptive Pacing Standard Rate Adaptive Pacing No Rate Adaptive Pacing Total
Hide Arm/Group Description Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up. Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up. Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up. Total of all reporting groups
Overall Number of Baseline Participants 741 369 381 1491
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 741 participants 369 participants 381 participants 1491 participants
73.5  (11.7) 72.5  (12.0) 72.7  (12.4) 73.1  (12.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 741 participants 369 participants 381 participants 1491 participants
Female
308
  41.6%
178
  48.2%
190
  49.9%
676
  45.3%
Male
433
  58.4%
191
  51.8%
191
  50.1%
815
  54.7%
1.Primary Outcome
Title Performance of Activities of Daily Living Tests (6-minute Walk and Sweep)
Hide Description 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.
Time Frame within 45 days of enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
Patients requiring at least 80% pacing during both tests in the CLS and accelerometer pacing modes are included.
Arm/Group Title CLS Rate Adaptive Pacing Standard Rate Adaptive Pacing No Rate Adaptive Pacing
Hide Arm/Group Description:
Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.
Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.
Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Overall Number of Participants Analyzed 30 30 30
Mean (Standard Deviation)
Unit of Measure: repetitions
19.28  (9.70) 18.09  (9.36) 18.05  (9.86)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CLS Rate Adaptive Pacing, Standard Rate Adaptive Pacing
Comments The endpoint will compare the composite percent change in ADL performance for patients while their devices are programmed to CLS and accelerometer pacing modes, using the no rate adaptive pacing mode as the baseline. Null hypothesis: mean composite of percent change for patients with their device programmed to CLS is less than or equal to the mean composite of percent change for the same patients with their device in accelerometer.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 9.17
Confidence Interval (2-Sided) 95%
3.24 to 15.11
Parameter Dispersion
Type: Standard Deviation
Value: 15.90
Estimation Comments [Not Specified]
2.Primary Outcome
Title Pulse Pressure During Activities of Daily Living Tests (Orthostatic Test)
Hide Description 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.
Time Frame within 45 days of enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title CLS Rate Adaptive Pacing Standard Rate Adaptive Pacing No Rate Adaptive Pacing
Hide Arm/Group Description:
Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.
Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.
Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Overall Number of Participants Analyzed 56 56 56
Mean (Standard Deviation)
Unit of Measure: mmHg
48.13  (12.35) 50.00  (14.4) 50.54  (15.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CLS Rate Adaptive Pacing, Standard Rate Adaptive Pacing
Comments The purpose of endpoint was to evaluate the percent change in pulse pressure during test. The null hypothesis was the mean percent change for patients with their device programmed to CLS is greater or equal to the mean percent change for the same patients with their device in accelerometer.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.552
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -1.42
Confidence Interval (2-Sided) 95%
-6.17 to 3.33
Parameter Dispersion
Type: Standard Deviation
Value: 17.74
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection CLS Rate Adaptive Pacing, No Rate Adaptive Pacing
Comments The purpose of endpoint was to evaluate the percent change in pulse pressure during test. The null hypothesis was the mean percent change for patients with their device programmed to CLS is greater or equal to the mean percent change for the same patients with their device without rate adaptative pacing.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.505
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 1.91
Confidence Interval (2-Sided) 95%
-3.80 to 7.63
Parameter Dispersion
Type: Standard Deviation
Value: 21.34
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Quality of Life
Hide Description 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.
Time Frame baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects completing a QOL at both baseline and 12 month follow-up were included in an intention to treat analysis.
Arm/Group Title CLS Rate Adaptive Pacing Standard Rate Adaptive Pacing No Rate Adaptive Pacing
Hide Arm/Group Description:
Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.
Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.
Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Overall Number of Participants Analyzed 464 208 221
Mean (Standard Deviation)
Unit of Measure: score
-0.41  (10.38) 0.37  (10.38) -0.41  (9.35)
4.Secondary Outcome
Title Mode Reprogramming
Hide Description 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.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects completing at least one follow-up visit were analyzed using intention to treat.
Arm/Group Title CLS Rate Adaptive Pacing Standard Rate Adaptive Pacing No Rate Adaptive Pacing
Hide Arm/Group Description:
Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.
Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.
Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Overall Number of Participants Analyzed 499 221 238
Measure Type: Number
Unit of Measure: participants
Dual to single chamber 5 2 1
Single to dual chamber 5 0 1
5.Secondary Outcome
Title Atrial Fibrillation (AF) Burden
Hide Description AF burden was measured at 12 months as the percentage of total atrial beats that are at or above 160 bpm.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Percentage of atrial burden was collected for subjects utilizing dual chamber pacing that completing a 12-month follow-up visit.
Arm/Group Title CLS Rate Adaptive Pacing Standard Rate Adaptive Pacing No Rate Adaptive Pacing
Hide Arm/Group Description:
Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.
Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.
Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Overall Number of Participants Analyzed 409 183 212
Mean (Standard Deviation)
Unit of Measure: percentage of atrial beats
7.54  (20.75) 5.57  (16.81) 6.65  (19.86)
6.Secondary Outcome
Title Cardiac Symptoms
Hide Description Number of subjects exhibiting each cardiac symptom was determined at the 12 month follow-up visit.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects answering questions about current cardiac symptoms at the 12-month visit were included in this intention to treat analysis.
Arm/Group Title CLS Rate Adaptive Pacing Standard Rate Adaptive Pacing No Rate Adaptive Pacing
Hide Arm/Group Description:
Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.
Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.
Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Overall Number of Participants Analyzed 471 209 230
Measure Type: Number
Unit of Measure: participants
Fatigue 120 51 54
Dizzy Spells 62 31 29
Chest Pains 32 21 19
Weakness 77 30 30
Palpitations 55 30 24
Hypotension 14 7 9
Syncope 5 6 5
Shortness of Breath 94 46 47
7.Secondary Outcome
Title Change in New York Heart Association (NYHA) Class
Hide Description 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.
Time Frame baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects with NYHA classifications at both enrollment and at the 12-month visit were analyzed using intention to treat.
Arm/Group Title CLS Rate Adaptive Pacing Standard Rate Adaptive Pacing No Rate Adaptive Pacing
Hide Arm/Group Description:
Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.
Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.
Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Overall Number of Participants Analyzed 470 201 223
Measure Type: Number
Unit of Measure: participants
Improved 2 classes 7 0 1
Improved 1 class 56 25 16
No change 341 143 166
Worsened 1 class 65 32 40
Worsened 2 classes 1 1 0
8.Secondary Outcome
Title Change in 6-minute Walk Test Distance
Hide Description Change in number of 10 foot repetitions between baseline and 12-month visit were examined.
Time Frame baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects completing the 6 minute walk at both enrollment and at the 12-month visit were included in intention to treat analysis.
Arm/Group Title CLS Rate Adaptive Pacing Standard Rate Adaptive Pacing No Rate Adaptive Pacing
Hide Arm/Group Description:
Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.
Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.
Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Overall Number of Participants Analyzed 436 197 203
Mean (Standard Deviation)
Unit of Measure: repetitions
0.03  (3.63) 0.41  (3.36) 0.27  (3.95)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title CLS Rate Adaptive Pacing Standard Rate Adaptive Pacing No Rate Adaptive Pacing
Hide Arm/Group Description Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up. Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up. Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
All-Cause Mortality
CLS Rate Adaptive Pacing Standard Rate Adaptive Pacing No Rate Adaptive Pacing
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
CLS Rate Adaptive Pacing Standard Rate Adaptive Pacing No Rate Adaptive Pacing
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/741 (0.00%)      0/369 (0.00%)      0/381 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
CLS Rate Adaptive Pacing Standard Rate Adaptive Pacing No Rate Adaptive Pacing
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   44/741 (5.94%)      23/369 (6.23%)      19/381 (4.99%)    
Cardiac disorders       
Cardiac symptoms with Catheterization   18/741 (2.43%)  18 8/369 (2.17%)  8 5/381 (1.31%)  5
Lead revision   6/741 (0.81%)  7 4/369 (1.08%)  4 3/381 (0.79%)  3
Device explants (for any reason)   4/741 (0.54%)  4 4/369 (1.08%)  4 2/381 (0.52%)  2
Symptomatic arrhythmia requiring ablation   3/741 (0.40%)  3 2/369 (0.54%)  2 1/381 (0.26%)  1
Change in status requiring device upgrade   9/741 (1.21%)  9 2/369 (0.54%)  2 3/381 (0.79%)  3
Mitral valve replacement   1/741 (0.13%)  1 2/369 (0.54%)  2 0/381 (0.00%)  0
Pacemaker pocket revision   0/741 (0.00%)  0 0/369 (0.00%)  0 2/381 (0.52%)  2
Pacemaker change-out (not device related)   1/741 (0.13%)  1 0/369 (0.00%)  0 0/381 (0.00%)  0
Other cardiac procedure not captured in other groups   4/741 (0.54%)  4 6/369 (1.63%)  6 2/381 (0.52%)  2
Surgical and medical procedures       
Non-cardiac procedure performed   8/741 (1.08%)  8 3/369 (0.81%)  3 5/381 (1.31%)  5
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: CLEAR Study CSE
Organization: BIOTRONIK, Inc.
Phone: 503-451-8051
Layout table for additonal information
Responsible Party: Biotronik, Inc.
ClinicalTrials.gov Identifier: NCT00355797     History of Changes
Other Study ID Numbers: 20060536
First Submitted: July 21, 2006
First Posted: July 25, 2006
Results First Submitted: June 6, 2011
Results First Posted: June 27, 2011
Last Update Posted: December 20, 2012