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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P050023 S101/ PAS001 |
| Date Original Protocol Accepted |
07/21/2017
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| Date Current Protocol Accepted |
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| Study Name |
ProMRI ICD/CRT-D System
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| Device Name |
IPERIA 7 VR-T/INVENTRA 7 VR-T (DF-1); IPERIA 7 VR-T/INVENTRA 7 VR-T (DF4)
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| General Study Protocol Parameters |
| Study Design |
Enhanced Surveillance
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| Data Source |
New Data Collection
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| Comparison Group |
No Control
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| Analysis Type |
Descriptive
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| Detailed Study Protocol Parameters |
| Study Objectives |
Retrospective, observational, post-approval study.
To gather additional data to assess VF episode detection following MRI exposure as a condition of FDA approval. Secondarily, this post-approval study will provide additional data on the MRI mode programming following the MRI and LV pacing threshold changes between pre-MRI and one-month post-MRI.
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| Study Population |
All subjects implanted with a ProMRI ICD/CRT-D system and enabled with Home
Monitoring® in the United States
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| Sample Size |
Primary Objective 1:
An estimated 75% of US ICD implants are registered for Home Monitoring® and approximately 75% of those subjects regularly transmit device data. Applying these Home Monitoring® registration and transmission rate to the estimated US sales of the ProMRI ICD system, approximately 8437 ProMRI ICD subjects will be actively
monitored by Home Monitoring® within 3 years of product approval. With an estimated annual MRI scan rate of 10%, approximately 1702 will have at least one MRI scan
within 4 years post product approval. Annual true VF episode rate is approximately 2%. Applying the estimated 2% to the expected annual implant and MRI rates, results in approximately 16-34 subjects with a true VF episode occurring after an MRI scan within 5 years post-approval.
Primary Objective 2:
With a = 0.025, 1 - ß = 80%, an anticipated pacing threshold success rate of 99%, a performance goal of 95% and a one-sided exact binomial test, a sample size of n = 145 evaluable subjects with LV leads is required.
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| Key Study Endpoints |
Primary Objective:
Characterize VF detection following MRI exposure, as determined by an independent Clinical Events Committee, to ensure there is no delay in VF detection attributable to the MRI scan.
MRI induced Left Ventricular pacing threshold changes between Pre-MRI and One-Month post-MRI.
Secondary Objectives:
Characterize appropriate tachycardia detection and ICD therapy programming following MRI exposure.
Characterize changes in LV sensing and pacing impedance between pre-MRI and one-month post-MRI.
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| Follow-up Visits and Length of Follow-up |
When 50 patients implanted with the ProMRI ICD system with a documented post-MRI VF episode have been identified or 5-years post-approval, which ever comes first
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
The number of enrolled patients was defined as the number of patients implanted with a device that was required to be part of the post approval study and that was also registered on Home Monitoring. The total number of patients satisfying both conditions was 24,249. A subgroup of patients undergoing at least one MRI (1,208) was monitored for changes (pre vs. post MR) in LV pacing capture threshold and as well as potential MRI induced delays in VF Detection. Post MRI VF episodes occurred in 110 subjects.
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| Actual Number of Sites Enrolled |
No study sites were enrolled since the study was designed to be an enhance surveillance study that monitored periodic device transmissions via the firm’s Home Monitoring System. Transmissions of all patients were filtered based on pre-defined events.
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| Patient Follow-up Rate |
Patient follow up was not required. In fact, the patient data were de-identified and follow up was only required if the observed change in LV pacing capture threshold or delay in post MR VF therapy exceeded predefined thresholds. Since no such events occurred, follow up was not required.
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| Final Safety Findings |
The first endpoint was the proportion of subjects with a greater than or equal to 5.0 second delay in post- MRI VF detection attributable to the MRI scan as adjudicated by the CEC. For subjects with more than one VF episode post-MRI, only the first VF episode post-MR exposure classified as VF by the CEC contributed to the primary objective. The following hypothese was tested:
H0: The number of subjects with greater than or equal to 5.0 second post-MRI VF detection delay post-MRI is > 1.
HA: The number of subjects with greater than or equal to 5.0 second post-MRI VF detection delay post- MRI is less than or equal to 1.
A rejection of the null hypothesis would demonstrate that there is evidence that there is not more than 1 subject with delayed post-MRI VF detection.
A total of 45 unique ProMRI ICD/CRT-D subjects (40 ICD, 5 CRT-D) experiencing at least one post-MRI VF episode adjudicated as True VF contributed to the 106 total episodes, satisfying the objective criteria of evaluating a minimum of 25 ICD subjects. Analysis of the Primary Objective 1 results indicate rejection of the null hypothesis and acceptance of the alternative hypothesis as a post-MRI VF episode detection delay of greater than or equal to 5.0 seconds was not observed in the 45 evaluable subjects (0/45, 0%). Therefore, Primary Objective 1 is met and demonstrated no evidence of delay in VF episode detection following an MRI.
The second endpoint evaluated the proportion of LV pacing leads with a LV pacing threshold increase between Pre-MRI and One-Month (30 days) post-MRI. The threshold behavior of the LV lead was defined as a success if the increase is not larger than 1.0 V. For a clear and concise definition of “success” the following abbreviations was used:
PTA = LV pacing threshold at Pre-MRI
PTB = LV pacing threshold at 30 days post-MRI
Success was defined as:
PTB – PTA less than or equal to 1.0 V
The proportion (pPT) of pacing threshold successes was calculated by dividing the number of LV leads without a ventricular pacing threshold increase as defined above by the total number of all LV leads.
H0: The success rate pPT for LV leads is smaller than or equal to 95%: pPT less than or equal to 95%.
HA: The success rate pPT for LV leads is greater than 95%: pPT > 95%.
A rejection of the null hypothesis would demonstrate that there is evidence that pPT is greater than 95%.
Left ventricular pacing threshold differences between one-month post-MRI and pre-MRI were available for 92 subjects. The proportion of pacing threshold success is 100% with none of the 92 subjects demonstrating a pacing threshold increase of greater than 1.0V between the pre-MRI measurement and one month post-MRI measurement. An average change in LV pacing capture threshold of 0.03 (min: -0.2, max: 1.0) with a standard deviation of 0.154 was observed.
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| Final Effect Findings |
The primary effectiveness endpoint was defined as the proportion of subjects with appropriate restoration of
tachycardia detection and ICD therapy post-MRI. Home Monitoring alerts for tachycardia detection/ICD therapy disabled within 24 hours following MR exposure were observed during the study to monitor for non-compliance to the post-MRI workflow. If there was a Home Monitoring transmission gap within the first 24 hours post-MRI, the next successful Home Monitoring transmission was utilized for this analysis. It was expected that the proportion of subjects with appropriate restoration of tachycardia detection and ICD therapy would be greater than or equal to 90%.
Of the 1,208 subjects undergoing an MRI with an MRI mode activated 227 subjects have undergone more than one MRI with an MRI mode activated for a total of 1,512 MRI procedures. Tachycardia detection and ICD therapy was restored in 1,202 of 1,208 (99.5%) subjects and after a total of 1,506 of 1,512 (99.6%) MRI
Procedures; showing good compliance to the workflow.
The secondary effectiveness endpoint was defined as the proportion of subjects who experience LV sensing amplitude attenuation. LV R-wave amplitude attenuation was defined as an LV R-wave amplitude decrease (between pre-MRI follow-up and 30 days post-MRI) exceeding 50%. The proportion (pRsensing) was calculated by dividing the number of subjects with LV R-wave Sensing Attenuation by the total number of subjects.
Left ventricular R-wave sensing amplitude differences between one-month post-MRI and pre-MRI were available for 121 subjects. The proportion of LV R-wave amplitude attenuation between pre- and one-month post-MRI measurements is 0.8% (mean 0.14 mV, Stdev 2.39 mV, min -15 mV, median 0 mV, max 8.4 mV) Only one subject reported an LV R-wave attenuation exceeding 50% of measured pre-MRI values.
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| Study Strengths & Weaknesses |
The study design allowed the capture of rare events in a post market setting by monitoring > 24,000 patient in a de-identified data base. The event rate of post MRI VF was <0.19%, not observable in a traditional pre-market study design.
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| Recommendations for Labeling Changes |
Labeling update not required
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