Trial Outcomes & Findings for Effectiveness of Pacemaker With Closed Loop Stimulation Compared to Pacemakers With and Without Standard Rate Response (NCT NCT00355797)

NCT ID: NCT00355797

Last Updated: 2012-12-20

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 1491 participants
• Primary outcome timeframe: within 45 days of enrollment
• Results posted on: 2012-12-20

Participant Flow

Participant milestones

Measure	CLS Rate Adaptive Pacing Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.	Standard Rate Adaptive Pacing Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.	No Rate Adaptive Pacing Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Overall Study STARTED	741	369	381
Overall Study COMPLETED	501	221	239
Overall Study NOT COMPLETED	240	148	142

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	CLS Rate Adaptive Pacing n=741 Participants Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.	Standard Rate Adaptive Pacing n=369 Participants Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.	No Rate Adaptive Pacing n=381 Participants Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.	Total n=1491 Participants Total of all reporting groups
Age Continuous	73.5 years STANDARD_DEVIATION 11.7 • n=5 Participants	72.5 years STANDARD_DEVIATION 12.0 • n=7 Participants	72.7 years STANDARD_DEVIATION 12.4 • n=5 Participants	73.1 years STANDARD_DEVIATION 12.0 • n=4 Participants
Sex: Female, Male Female	308 Participants n=5 Participants	178 Participants n=7 Participants	190 Participants n=5 Participants	676 Participants n=4 Participants
Sex: Female, Male Male	433 Participants n=5 Participants	191 Participants n=7 Participants	191 Participants n=5 Participants	815 Participants n=4 Participants

PRIMARY outcome

Timeframe: within 45 days of enrollment

Population: Patients requiring at least 80% pacing during both tests in the CLS and accelerometer pacing modes are included.

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.

Outcome measures

Measure	CLS Rate Adaptive Pacing n=30 Participants Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.	Standard Rate Adaptive Pacing n=30 Participants Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.	No Rate Adaptive Pacing n=30 Participants Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Performance of Activities of Daily Living Tests (6-minute Walk and Sweep)	19.28 repetitions Standard Deviation 9.70	18.09 repetitions Standard Deviation 9.36	18.05 repetitions Standard Deviation 9.86

PRIMARY outcome

Timeframe: within 45 days of enrollment

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.

Outcome measures

Measure	CLS Rate Adaptive Pacing n=56 Participants Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.	Standard Rate Adaptive Pacing n=56 Participants Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.	No Rate Adaptive Pacing n=56 Participants Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Pulse Pressure During Activities of Daily Living Tests (Orthostatic Test)	48.13 mmHg Standard Deviation 12.35	50.00 mmHg Standard Deviation 14.4	50.54 mmHg Standard Deviation 15.23

SECONDARY outcome

Timeframe: baseline and 12 months

Population: Subjects completing a QOL at both baseline and 12 month follow-up were included in an intention to treat analysis.

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.

Outcome measures

Measure	CLS Rate Adaptive Pacing n=464 Participants Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.	Standard Rate Adaptive Pacing n=208 Participants Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.	No Rate Adaptive Pacing n=221 Participants Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Change in Quality of Life	-0.41 score Standard Deviation 10.38	0.37 score Standard Deviation 10.38	-0.41 score Standard Deviation 9.35

SECONDARY outcome

Timeframe: 12 months

Population: Subjects completing at least one follow-up visit were analyzed using intention to treat.

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.

Outcome measures

Measure	CLS Rate Adaptive Pacing n=499 Participants Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.	Standard Rate Adaptive Pacing n=221 Participants Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.	No Rate Adaptive Pacing n=238 Participants Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Mode Reprogramming Dual to single chamber	5 participants	2 participants	1 participants
Mode Reprogramming Single to dual chamber	5 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: 12 months

Population: Percentage of atrial burden was collected for subjects utilizing dual chamber pacing that completing a 12-month follow-up visit.

AF burden was measured at 12 months as the percentage of total atrial beats that are at or above 160 bpm.

Outcome measures

Measure	CLS Rate Adaptive Pacing n=409 Participants Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.	Standard Rate Adaptive Pacing n=183 Participants Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.	No Rate Adaptive Pacing n=212 Participants Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Atrial Fibrillation (AF) Burden	7.54 percentage of atrial beats Standard Deviation 20.75	5.57 percentage of atrial beats Standard Deviation 16.81	6.65 percentage of atrial beats Standard Deviation 19.86

SECONDARY outcome

Timeframe: 12 months

Population: All subjects answering questions about current cardiac symptoms at the 12-month visit were included in this intention to treat analysis.

Number of subjects exhibiting each cardiac symptom was determined at the 12 month follow-up visit.

Outcome measures

Measure	CLS Rate Adaptive Pacing n=471 Participants Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.	Standard Rate Adaptive Pacing n=209 Participants Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.	No Rate Adaptive Pacing n=230 Participants Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Cardiac Symptoms Fatigue	120 participants	51 participants	54 participants
Cardiac Symptoms Dizzy Spells	62 participants	31 participants	29 participants
Cardiac Symptoms Chest Pains	32 participants	21 participants	19 participants
Cardiac Symptoms Weakness	77 participants	30 participants	30 participants
Cardiac Symptoms Palpitations	55 participants	30 participants	24 participants
Cardiac Symptoms Hypotension	14 participants	7 participants	9 participants
Cardiac Symptoms Syncope	5 participants	6 participants	5 participants
Cardiac Symptoms Shortness of Breath	94 participants	46 participants	47 participants

SECONDARY outcome

Timeframe: baseline and 12 months

Population: Subjects with NYHA classifications at both enrollment and at the 12-month visit were analyzed using intention to treat.

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.

Outcome measures

Measure	CLS Rate Adaptive Pacing n=470 Participants Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.	Standard Rate Adaptive Pacing n=201 Participants Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.	No Rate Adaptive Pacing n=223 Participants Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Change in New York Heart Association (NYHA) Class Improved 2 classes	7 participants	0 participants	1 participants
Change in New York Heart Association (NYHA) Class Improved 1 class	56 participants	25 participants	16 participants
Change in New York Heart Association (NYHA) Class No change	341 participants	143 participants	166 participants
Change in New York Heart Association (NYHA) Class Worsened 1 class	65 participants	32 participants	40 participants
Change in New York Heart Association (NYHA) Class Worsened 2 classes	1 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: baseline and 12 months

Population: Subjects completing the 6 minute walk at both enrollment and at the 12-month visit were included in intention to treat analysis.

Change in number of 10 foot repetitions between baseline and 12-month visit were examined.

Outcome measures

Measure	CLS Rate Adaptive Pacing n=436 Participants Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.	Standard Rate Adaptive Pacing n=197 Participants Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.	No Rate Adaptive Pacing n=203 Participants Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Change in 6-minute Walk Test Distance	0.03 repetitions Standard Deviation 3.63	0.41 repetitions Standard Deviation 3.36	0.27 repetitions Standard Deviation 3.95

Adverse Events

CLS Rate Adaptive Pacing

Serious events: 0 serious events

Other events: 44 other events

Deaths: 0 deaths

Standard Rate Adaptive Pacing

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

No Rate Adaptive Pacing

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	CLS Rate Adaptive Pacing n=741 participants at risk Pacemaker programmed with Closed Loop Stimulation (CLS) rate adaptive technology for long-term study follow-up.	Standard Rate Adaptive Pacing n=369 participants at risk Pacemaker programmed with standard rate adaptive technology (R, accelerometer) for long-term study follow-up.	No Rate Adaptive Pacing n=381 participants at risk Pacemaker programmed with no rate adaption (DDD) for long-term study follow-up.
Cardiac disorders Cardiac symptoms with Catheterization	2.4% 18/741 • Number of events 18	2.2% 8/369 • Number of events 8	1.3% 5/381 • Number of events 5
Cardiac disorders Lead revision	0.81% 6/741 • Number of events 7	1.1% 4/369 • Number of events 4	0.79% 3/381 • Number of events 3
Surgical and medical procedures Non-cardiac procedure performed	1.1% 8/741 • Number of events 8	0.81% 3/369 • Number of events 3	1.3% 5/381 • Number of events 5
Cardiac disorders Device explants (for any reason)	0.54% 4/741 • Number of events 4	1.1% 4/369 • Number of events 4	0.52% 2/381 • Number of events 2
Cardiac disorders Symptomatic arrhythmia requiring ablation	0.40% 3/741 • Number of events 3	0.54% 2/369 • Number of events 2	0.26% 1/381 • Number of events 1
Cardiac disorders Change in status requiring device upgrade	1.2% 9/741 • Number of events 9	0.54% 2/369 • Number of events 2	0.79% 3/381 • Number of events 3
Cardiac disorders Mitral valve replacement	0.13% 1/741 • Number of events 1	0.54% 2/369 • Number of events 2	0.00% 0/381
Cardiac disorders Pacemaker pocket revision	0.00% 0/741	0.00% 0/369	0.52% 2/381 • Number of events 2
Cardiac disorders Pacemaker change-out (not device related)	0.13% 1/741 • Number of events 1	0.00% 0/369	0.00% 0/381
Cardiac disorders Other cardiac procedure not captured in other groups	0.54% 4/741 • Number of events 4	1.6% 6/369 • Number of events 6	0.52% 2/381 • Number of events 2

Additional Information

CLEAR Study CSE

BIOTRONIK, Inc.

Phone: 503-451-8051

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60