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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P960040 S385/ PAS001 |
| Date Original Protocol Accepted |
08/07/2017
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| Date Current Protocol Accepted |
11/17/2017
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| Study Name |
SMART-MSP PAS
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| Device Name |
NG4 Family of Pulse Generators ICDS.
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| General Study Protocol Parameters |
| Study Design |
Randomized Clinical Trial
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| Data Source |
New Data Collection
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| Comparison Group |
Device Subjects Serve as Own 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 |
Evaluate the effectiveness of Boston Scientific (BSC)’s LV MSP (Left Ventricular MultiSite Pacing) feature in the Resonate family of CRT-D devices1 and confirm safety in a post approval study when used in accordance with its approved labeling.
Prospective, multi-center, single arm, post approval study to be conducted in the United States.
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| Study Population |
Subjects who are non-responders to conventional Biventricular (BiV) CRT-D therapy
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| Sample Size |
Primary Safety Endpoint:
The overall study sample size of 586 subjects is driven by the primary effectiveness endpoint. The sample size of 61 subjects is required to evaluate the Primary Safety Endpoint. Since a power calculation cannot be directly calculated for a one group Kaplan-Meier analysis, an exact test was used. A power calculation using a sample size of 61 subjects as the non-responders with the LV MSP on was calculated based on a one-sided exact test for a single binomial proportion, using SAS Version 9.4 with the following assumptions:
Performance goal = 90%
Expected LV MSP feature-related CFR rate between 6 and 12 Month Visit = 98%
Significance level = 5%
Power = 80%
Primary Effectiveness Endpoint:
The sample size of 110 subjects with paired CCS calculation from the 6 Month Visit through 12 Month Visit is required to evaluate the Primary Effectiveness Endpoint. For further details on overall sample size and attrition see Figure 12.3-1. The overall study sample size is
driven by the primary effectiveness endpoint. This sample size was calculated based on a one-sided exact test for a single binomial proportion, using SAS Version 9.4 with the following assumptions:
Performance goal = 5%
Expected performance = 15%
One-sided significance level = 5%
Power = 95%
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| Key Study Endpoints |
The primary safety endpoint for SMART-MSP is LV MSP feature-related complication-free rate
between the 6 Month Visit and the 12 Month Visit in non-responders with the LV MSP turned on for any duration and the primary effectiveness endpoint is Proportion of the LV MSP Group subjects with Improved Clinical Composite Score (CCS) from the 6 Month Visit through the 12 Month Visit.
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| Follow-up Visits and Length of Follow-up |
The length of follow-up is maximum of 12 months.
Subjects determined to be a responder at their 6 month visit will complete the study. Subjects in the non-responder group, including those subjects who have no LV MSP turned on, will complete the study at their 12 month visit.
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
594 patients
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| Actual Number of Sites Enrolled |
52 sites
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| Patient Follow-up Rate |
The mean months +/- SD of all enrolled subjects was 7.0 +/- 3.1.
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| Final Safety Findings |
The LV MSP feature related complication-free rate was 99.0% with a lower 95% confidence limit of 94.9%, which was higher than the performance goal of 90%.
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| Final Effect Findings |
The proportion of Non-Responder subjects with an improved CCS from 6-12 months was 51.3% with a lower 95% confidence limit of 41.4%, which was higher than the performance goal of 5%.
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| Study Strengths & Weaknesses |
The firm has fulfilled the conditions of approval by completing the study as planned. There are no safety concerns raised by this large study. Detailed review of the adverse events shows no specific adverse event types are increased over what we might see in this population. Overall, the MSP
approach shows a substantial minority of subjects benefitted.
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| Recommendations for Labeling Changes |
Yes, a labeling change is recommended. The study results are favorable, free of new safety signals and show a promising effectiveness signal. These results should be included in an update to the label.
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