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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P970029 / PAS001 |
| Date Original Protocol Accepted |
10/20/2009
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| Date Current Protocol Accepted |
10/20/2009
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| Study Name |
TMR
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| Device Name |
TMR HOLMIUM LASER SYSTEM
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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 |
Historical Control
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| Analysis Type |
Analytical
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| Study Population |
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
The study was initially designed as a randomized study comparing 300 eligible patients receiving TMR immediately to 300 patients receiving TMR following a 30-day delay period. Enrollment in this study as originally designed was not successful. The postmarket study was redesigned as a nonrandomized registry with a sample size of 500. Eligible patients can be enrolled prospectively and retrospectively.
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| Study Population |
Study Population: Patients who may benefit from maintenance of AV synchrony. Indication: Transmyocardial revascularization with the Eclipse TMR System is indicated for treatment of adult patients with ejection fractions of 25% or more and with stable angina (Canadian Cardiovascular Society Class 4). These patients also have a region of the myocardium with reversible ischemia, however are not candidates for bypass surgery or angioplasty.
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| Sample Size |
500 patients, 25 sites
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| Key Study Endpoints |
The primary endpoint of this study is all-cause 30-day mortality. An additional analysis to be reported in this study is the 30-day risk of major adverse cardiovascular events, defined as the incidence of cardiac-related death, myocardial infarction Q-wave and non Q-wave), congestive heart failure/ cerebrovascular accident, and serious arrhythmia.
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| Follow-up Visits and Length of Follow-up |
The patients will be followed in the hospital and 30 calendar days following the TMR procedure or to discharge, whichever is later.
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| Interim or Final Data Summary |
| Interim Results |
The 30-day all-cause mortality risk in the PAS is 2.8% (8/358) [2.8% (2/72) prospectively enrolled and 2.1% (6/286) retrospectively enrolled). Six deaths were cardiac related and 4 deaths were not. Of the 26 patients removed from the study, 2 died within 30 days one death was cardiac related. Baseline demographic variables and clinical risk factors were included in an analysis to determine predictors of 30-day all-cause mortality. A multivariable logistic analysis showed there were no variables significant at the p = 0.05 level. There were 43 major adverse cardiac events that occurred in 33 patients for an overall major adverse cardiac event rate of 9.2% (33/358). Of the 33 patients with at least one major adverse cardiac event, 7 (9.7%) patients were enrolled prospectively and 26 (9.1%) patients were enrolled retrospectively. Serious arrhythmia accounted for the majority of major advers cardiac events (6.7%). Among the 25 episodes of arrhythmia in 24 patients. 14 events occurred within 48-hours of the TMR procedure; 4 events occurred within 72-hours; and the remaining 7 events occurred between day 4 and day 29 days post TMR procedure. Of the 26 patients who were removed from the study as of this report, two experienced a major adverse cardiac event (arrhythmia). The results of the analyses shown in Table 8 indicate that only the number of TMR channels is a statistically significant independent predictor of 30- day major adverse cardiac event. The number of channel counts was also further analyzed, grouped by increments of 10, to determine if a trend existed toward increased major adverse cardiac event with increased numbers of TMR Channels.
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| Actual Number of Patients Enrolled |
358
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| Actual Number of Sites Enrolled |
20
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| Patient Follow-up Rate |
100%
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| Final Safety Findings |
In the Post-Approval Study of 358 patients treated with the Sologrip or Pearl 5.0 Handpieces, patients with ejection fractions ¡Â30% were at higher risk of death at 30-days (11.1%) compared to patients with ejection fractions >30% (1.5%). The number of TMR channels is a statistically significant independent predictor of 30- day MACE. The 30-day mortality proportion in the PAS (2.8%) is lower than the pre-approval study (5.3%).
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| Final Effect Findings |
The post-approval study was not designed to examine effectiveness.
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| Study Strengths & Weaknesses |
Strength: The study included 358 patients providing a fair characterization of the 30-day mortality and MACE proportions.
Weakness: The post-approval study included a large proportion of retrospectively (n=286) (i.e., since the time of the original FDA approval [March 1999]) enrolled participants compared to the prospectively (n=72) enrolled.
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| Recommendations for Labeling Changes |
In the Post-Approval Study of 358 patients treated with the Sologrip or Pearl 5.0
Handpieces, patients with ejection fractions ¡Â30% were at higher risk of death (11.1%)
compared to patients with ejection fractions >30% (1.5%).
A typical application of the device creates the lowest number of TMR channels yielding a density of 1 TMR channel/cm©÷ in ischemic myocardium. The benefits of creating larger numbers of channels (> 40), either to treat broader areas of ischemia or to achieve a higher channel density, should be weighed against the potential risks of adverse events for each patient.
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