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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P980050 / PAS001 |
| Date Original Protocol Accepted |
03/26/2003
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| Date Current Protocol Accepted |
03/26/2003
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| Study Name |
RESPECT
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| Device Name |
MEDTRONIC(R) JEWEL(R) AF 7250 DUAL CHAMBER IMPLANTABLE CARDIOVERTER DEFIBRILLATOR, MODEL 9961 PROGRAMMER APPLICATION SOF
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
New Data Collection
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| Comparison Group |
Concurrent Control
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| Analysis Type |
Analytical
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| Study Population |
Adolescent: 13-18 yrs,
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
The post-approval study is a multi-center, randomized, single-blind, crossover prospective clinical study. All subjects in the study receive the device. Patients meeting criteria are enrolled and implanted with a Medtronic AT500 or EnRhythm system and a high septal (Bachmann's Bundle region) atrial lead placement. Three months of observation are followed by randomization to first having pacing on or off. Six months of the randomized intervention pacing are followed by the opposite pacing condition.
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| Study Population |
Study population: Patients who meet the Class I or Class II implantation criteria for dual chamber pacing according to the guidelines described by American College of Cardiology/American Heart Association and patients who have had documented paroxysmal atrial tachycardia. Indication: The Medtronic AT500 DDDRP and model P1501DR EnRhythm pacing systems are indicated for rate adaptive pacing in patients who may benefit from increased pacing rates concurrent with increases in activity. Both systems are also indicated for dual chamber and atrial tracking modes in patients who may benefit from maintenance of atrioventricular synchrony. Dual chamber modes are specifically indicated for treatment of conduction disorders that require restoration of both rate and atrioventricular synchrony.
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| Sample Size |
400 subjects, 90 sites
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| Key Study Endpoints |
Endpoints include adverse events (patient death, serious injury or device malfunction).
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| Follow-up Visits and Length of Follow-up |
Baseline data are collected prior to implant. Clinical data are collected at the time of enrollment, implant/pre-hospital discharge, at 3 months (with randomization), 9 months (after 6 months ON or OFF), and 15 months post-implant (after crossover and additional 6 months OFF or ON). Adverse event data are also captured via phone every two weeks through the randomization period.
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| Interim or Final Data Summary |
| Interim Results |
There were 11 deaths to date and 18 total adverse events have occurred to date. Adverse events included: 6 dislodgements, 3 change in sensing threshold/loss of capsure, 2 dizziness, and 1 each of pleural effusion, pneumothorax, infection/errosion, atrial fibrillation during lead placement, no atrial sensing during lead placement, arm swelling, and shortness of breath/nausea/vomitting.
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| Actual Number of Patients Enrolled |
402 patients (both randomized and non randomized)
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| Actual Number of Sites Enrolled |
37 centers in the United States and Canada.
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| Patient Follow-up Rate |
Cumulative follow-up for ON Programming was 1389 months; for OFF programming was1296 months.
Average follow-up for ON Programming was 5.6 months; for OFF programming was 5.3 months.
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| Final Safety Findings |
The study did not provide any data to suggest there are patient safety concerns associated with the use of intervention pacing therapies in the patient population. A total of 19 adverse events (AEs) were reported. Of the AEs reported, 5% (7/132) occurred in the ON-OFF subjects, 6% (8/124) in the OFF-ON subjects and 3% (4/144) in the non-randomized subjects. Procedure related AEs were reported in 5% (6/132) and 2% (3/124) of ON-OFF and OFF-ON subjects, respectively. System related AEs were reported in 4% (5/132) and 5% (6/124) of ON-OFF and OFF-ON subjects respectively. A total of 11 deaths were reported among the 400 subjects with available data. Ten of the deaths occurred while the intervention pacing therapies were programmed OFF and 1 death occurred while the intervention pacing therapies were programmed ON. None of the deaths were related to the device, the system, or procedure. The relatedness of 1 death to device or system was unknown.
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| Final Effect Findings |
Primary Objective
To demonstrate a reduction in the frequency of symptomatic AT/AF episodes as measured by the Patient Assistant.
Among the 222 subjects with available device data for both randomized study periods, the average ON minus OFF difference in symptomatic AT/AF episode rate was 0.1 episodes per month (upper 1-sided 95% CI 0.5%). The upper 1-sided 95% confidence interval for the difference was > 0. Therefore the primary objective was not met (P = 0.629).
Secondary Objectives
1. Evaluated subject symptoms with the AF symptom checklist.
A total of 211 out of 256 randomized subjects completed the AF symptom checklist (subject perception of frequency and 16 arrhythmia related symptoms) at 9 and 15 months visits. No difference in the frequency (P = 0.165), severity (P = 0.421) or number of AF symptoms (P = 0.172) was observed during periods of ON versus OFF programming.
2. Evaluated the time to first cardioversion for AF.
Among the 256 subjects, 15 cardioversion attempts in 11 subjects during 1473 months of follow-up with ON programming, and 17 cardioversion attempts in 13 subjects during 1383 months of follow-up with OFF programming were reported. There was no difference in the risk of cardioversion for AF between ON and OFF programming (P=0.603).
3. Evaluated the intervention pacing feature effect on AT/AF burden.
A total of 225 of 256 randomized subjects had AT/AF burden data available for both randomized periods. An average of 3.6 h/day of AT/AF burden during ON programming compared to 3.5 h/day of AT/AF burden during OFF programming was observed (P=0.499). The results were similar across all subject subgroups.
4. Evaluated the intervention pacing feature effect on AT/AF symptomatic days.
This evaluation included only randomized subjects implanted with the AT500 device since only the AT500 device recorded Patient Assistant activations. Fifty-eight (58) of 69 randomized subjects implanted with the AT500 device had device data available in both randomized periods. During ON programming symptomatic AT/AF was recorded on 5.3% of randomized days versus 4.8% of randomized days during OFF programming (P=0.966).
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| Study Strengths & Weaknesses |
A well designed randomized single-blind multicenter study. The ON-OFF and OFF-ON programming arms were well balanced with regard to baseline characteristics indicating that the randomization was satisfactory. Exceptions included gender (higher percentage of females randomized to ON-OFF) and age (ON-OFF group was older). However, since the study design was a crossover, each subject served as his/her own control and the potential effect of differences in subject characteristics at baseline were minimized for the pre-specified analyses.
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| Recommendations for Labeling Changes |
Yes, there were recommendations to the labeling to update with data from the post-approval study results.
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