Trial Outcomes & Findings for Seizure Detection and Automatic Magnet Mode Performance Study (NCT NCT01325623)
NCT ID: NCT01325623
Last Updated: 2016-01-22
Results Overview
Subjects were admitted to the EMU and underwent standard continuous data collection of vEEG and ECG for 3 to 5 days. If a seizure occurred during the EMU stay, clinical investigators annotated the start and stop times, the type of seizure, the presumed seizure onset location, and the lobe of origin as applicable. Following the EMU data collection phase of the trial, the de-identified, continuous electronic records (per patient) from the EMU period were provided to an independent and blinded triple review panel. This panel evaluated the EEG data and annotated seizure onset, seizure offset, and a description of seizure type. In the absence of video, seizure types could only be specified as: partial (particular type not denoted), generalized (non-absence), absence, or partial with secondary generalization.
COMPLETED
NA
31 participants
Epilepsy Monitoring Unit Stay
2016-01-22
Participant Flow
Eligible subjects were at least 18 years old, with a clinical diagnosis of medically refractory epilepsy dominated by partial seizures suitable for implantation with the Model 106 VNS Therapy System and a history of ictal tachycardia, defined as heart rate above 100 bpm during a seizure and at least a 55% increase or 35 bpm increase from baseline.
A total of 35 subjects were screened; (4) did not meet study criteria, (31) were treated/implanted with the AspireSR® VNS Therapy® System, of which (1) was implanted with version 1 of the AspireSR® VNS Therapy® System and (30) were implanted with version 2 (= ITT population).
Participant milestones
| Measure |
Enrolled and Treated Population (Safety Population)
Consists of all patients who provided consent and were implanted with the AspireSR VNS Therapy System version 1 or version 2. The safety population will be used for all safety analyses. (N=31 subjects).
In version 2 of the AspireSR VNS Therapy System, the TVS diodes (present in version 1) were removed from the electrical circuit to address the accumulation of electrical charge on the sensing node (e.g. generator-can) following delivery of a stimulation.
|
|---|---|
|
Overall Study
STARTED
|
31
|
|
Overall Study
COMPLETED
|
28
|
|
Overall Study
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
Enrolled and Treated Population (Safety Population)
Consists of all patients who provided consent and were implanted with the AspireSR VNS Therapy System version 1 or version 2. The safety population will be used for all safety analyses. (N=31 subjects).
In version 2 of the AspireSR VNS Therapy System, the TVS diodes (present in version 1) were removed from the electrical circuit to address the accumulation of electrical charge on the sensing node (e.g. generator-can) following delivery of a stimulation.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
Baseline Characteristics
Seizure Detection and Automatic Magnet Mode Performance Study
Baseline characteristics by cohort
| Measure |
VNS Therapy (Safety Population)
n=31 Participants
The safety population consists of all patients who provided consent and were implanted with the AspireSR VNS Therapy System version 1 or version 2.
|
|---|---|
|
Age, Continuous
|
39.6 years
STANDARD_DEVIATION 13.4 • n=5 Participants
|
|
Age, Customized
|
38 years
n=5 Participants
|
|
Age, Customized
18-29 years
|
10 participants
n=5 Participants
|
|
Age, Customized
30-39 years
|
8 participants
n=5 Participants
|
|
Age, Customized
40-49 years
|
5 participants
n=5 Participants
|
|
Age, Customized
50-59 years
|
5 participants
n=5 Participants
|
|
Age, Customized
60 years or older
|
3 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
31 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
3 participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
10 participants
n=5 Participants
|
|
Region of Enrollment
Norway
|
1 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
7 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
10 participants
n=5 Participants
|
|
Cognitive Status
Normal
|
20 participants
n=5 Participants
|
|
Cognitive Status
Minimal Impairment
|
8 participants
n=5 Participants
|
|
Cognitive Status
Moderate Impairment
|
3 participants
n=5 Participants
|
|
Cognitive Status
Severe Impairment
|
0 participants
n=5 Participants
|
|
Age at Epilepsy Onset
|
15.9 years
STANDARD_DEVIATION 10.9 • n=5 Participants
|
|
Previous Brain or Epilepsy Surgery
No
|
22 participants
n=5 Participants
|
|
Previous Brain or Epilepsy Surgery
Yes
|
9 participants
n=5 Participants
|
|
Etiology
Idiopathic
|
3 participants
n=5 Participants
|
|
Etiology
Symptomatic
|
16 participants
n=5 Participants
|
|
Etiology
Cryptogenic
|
12 participants
n=5 Participants
|
|
Family History of Seizures
No
|
24 participants
n=5 Participants
|
|
Family History of Seizures
Yes
|
7 participants
n=5 Participants
|
|
Seizures with Auras in the Past 2 Months
No
|
15 participants
n=5 Participants
|
|
Seizures with Auras in the Past 2 Months
Yes
|
16 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Epilepsy Monitoring Unit StayPopulation: ITT Population: consists of all patients implanted with the AspireSR VNS Therapy System version 2 and who have any EMU record.
Subjects were admitted to the EMU and underwent standard continuous data collection of vEEG and ECG for 3 to 5 days. If a seizure occurred during the EMU stay, clinical investigators annotated the start and stop times, the type of seizure, the presumed seizure onset location, and the lobe of origin as applicable. Following the EMU data collection phase of the trial, the de-identified, continuous electronic records (per patient) from the EMU period were provided to an independent and blinded triple review panel. This panel evaluated the EEG data and annotated seizure onset, seizure offset, and a description of seizure type. In the absence of video, seizure types could only be specified as: partial (particular type not denoted), generalized (non-absence), absence, or partial with secondary generalization.
Outcome measures
| Measure |
Reported by Investigators
n=30 Participants
All seizures that occurred during EMU stay and that were identified by investigators.
|
Reported by Triple Review
n=30 Participants
All seizures that occurred during EMU stay and that were identified by triple review post EMU.
|
Total
n=30 Participants
Seizures from an ITT subject that were either identified by the investigator during EMU evaluation or during the triple review process of EEG data.
|
Generalized Tonic Clonic Sz
NHS3 Scores at Follow-Up Visits
|
SSQ Scores at 24 Months
Change From Baseline at Each Category
|
|---|---|---|---|---|---|
|
Summary of Seizures Reported by Investigators and Triple Review
All Seizure Types
|
87 Seizures
|
124 Seizures
|
211 Seizures
|
—
|
—
|
|
Summary of Seizures Reported by Investigators and Triple Review
Total Partial
|
82 Seizures
|
51 Seizures
|
133 Seizures
|
—
|
—
|
|
Summary of Seizures Reported by Investigators and Triple Review
Partial
|
8 Seizures
|
51 Seizures
|
59 Seizures
|
—
|
—
|
|
Summary of Seizures Reported by Investigators and Triple Review
Simple Partial
|
26 Seizures
|
0 Seizures
|
26 Seizures
|
—
|
—
|
|
Summary of Seizures Reported by Investigators and Triple Review
Complex Partial
|
31 Seizures
|
0 Seizures
|
31 Seizures
|
—
|
—
|
|
Summary of Seizures Reported by Investigators and Triple Review
Complex Partial with Secondary Generalization
|
17 Seizures
|
0 Seizures
|
17 Seizures
|
—
|
—
|
|
Summary of Seizures Reported by Investigators and Triple Review
Primary Generalized
|
0 Seizures
|
43 Seizures
|
43 Seizures
|
—
|
—
|
|
Summary of Seizures Reported by Investigators and Triple Review
Sub-Clinical
|
1 Seizures
|
0 Seizures
|
1 Seizures
|
—
|
—
|
|
Summary of Seizures Reported by Investigators and Triple Review
Unknown
|
3 Seizures
|
0 Seizures
|
3 Seizures
|
—
|
—
|
|
Summary of Seizures Reported by Investigators and Triple Review
Other
|
1 Seizures
|
0 Seizures
|
1 Seizures
|
—
|
—
|
|
Summary of Seizures Reported by Investigators and Triple Review
Unclassified Seizure
|
0 Seizures
|
30 Seizures
|
30 Seizures
|
—
|
—
|
PRIMARY outcome
Timeframe: Epilepsy Monitoring Unit (EMU) StayPopulation: Patients from the ITT population who completed the EMU evaluation and that had at least one reported seizure during the EMU evaluation that was confirmed by triple review; (Investigator Reported Seizures + Triple Review).
Sensitivity is the total number of seizures detected divided by the total number of seizures during EMU stay.Data used to support sensitivity analyses included digital ECG/EEG files,corresponding M106 device downloads,and CRF data.Seizure and non-seizure EEG segments were provided to independent reviewers to confirm seizure occurrence and define EEG seizure onset times.Seizure onset times were then compared with observed M106 device detections at the detection threshold setting for AutoStim that the patient was randomized to(SDA 2;60%,SDA 4;40%,SDA 6;20%).Sensitivity is only reported if the heart rate surpassed the programmed detection threshold.Number of participants is total number of subjects who had seizures during the EMU stay. An "Ictal tachycardia Seizure" is a seizure with Ictal Heart rate \>= 100 bpm \& at least 55% increase, or 35 bpm increase from baseline) Bootstrap confidence intervals using 3000 bootstrap samples. n=total number of seizures; N= number of participants
Outcome measures
| Measure |
Reported by Investigators
n=18 Participants
All seizures that occurred during EMU stay and that were identified by investigators.
|
Reported by Triple Review
All seizures that occurred during EMU stay and that were identified by triple review post EMU.
|
Total
Seizures from an ITT subject that were either identified by the investigator during EMU evaluation or during the triple review process of EEG data.
|
Generalized Tonic Clonic Sz
NHS3 Scores at Follow-Up Visits
|
SSQ Scores at 24 Months
Change From Baseline at Each Category
|
|---|---|---|---|---|---|
|
Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
Ictal Tachycardia Seizures, SDA 2 (n=1; N=1)
|
100 percentage of True Positive Detections
Confidence interval not computable where the mean sensitivity equals to 100%, or where number of patients within the setting is less than or equal to 2 (acceleration cannot be calculated).
|
—
|
—
|
—
|
—
|
|
Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
Ictal Tachycardia Seizures, SDA 4 (n=8; N=2)
|
75 percentage of True Positive Detections
Confidence interval not computable where the mean sensitivity equals to 100%, or where number of patients within the setting is less than or equal to 2 (acceleration cannot be calculated).
|
—
|
—
|
—
|
—
|
|
Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
Ictal Tachycardia Seizures, SDA 6 (n=2; N=2)
|
100 percentage of True Positive Detections
Confidence interval not computable where the mean sensitivity equals to 100%, or where number of patients within the setting is less than or equal to 2 (acceleration cannot be calculated).
|
—
|
—
|
—
|
—
|
|
Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
>= 70% heart rate increase, SDA 4 (n=3; N=2)
|
66.7 percentage of True Positive Detections
Confidence interval not computable where the mean sensitivity equals to 100%, or where number of patients within the setting is less than or equal to 2 (acceleration cannot be calculated).
|
—
|
—
|
—
|
—
|
|
Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
>= 60% heart rate increase, SDA 2 (n=1; N=1)
|
100 percentage of True Positive Detections
Confidence interval not computable where the mean sensitivity equals to 100%, or where number of patients within the setting is less than or equal to 2 (acceleration cannot be calculated).
|
—
|
—
|
—
|
—
|
|
Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
>= 60% heart rate increase, SDA 4 (n=4; N=2)
|
50 percentage of True Positive Detections
Confidence interval not computable where the mean sensitivity equals to 100%, or where number of patients within the setting is less than or equal to 2 (acceleration cannot be calculated).
|
—
|
—
|
—
|
—
|
|
Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
>= 50% heart rate increase, SDA 4 (n=6; N=2)
|
66.7 percentage of True Positive Detections
Confidence interval not computable where the mean sensitivity equals to 100%, or where number of patients within the setting is less than or equal to 2 (acceleration cannot be calculated).
|
—
|
—
|
—
|
—
|
|
Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
>= 50% heart rate increase, SDA 6 (n=1; N=1)
|
100 percentage of True Positive Detections
Confidence interval not computable where the mean sensitivity equals to 100%, or where number of patients within the setting is less than or equal to 2 (acceleration cannot be calculated).
|
—
|
—
|
—
|
—
|
|
Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
>= 40% heart rate increase, SDA 4 (n=9; N=2))
|
66.7 percentage of True Positive Detections
Confidence interval not computable where the mean sensitivity equals to 100%, or where number of patients within the setting is less than or equal to 2 (acceleration cannot be calculated).
|
—
|
—
|
—
|
—
|
|
Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
>= 40% heart rate increase, SDA 6 (n=4; N=3))
|
100 percentage of True Positive Detections
Confidence interval not computable where the mean sensitivity equals to 100%, or where number of patients within the setting is less than or equal to 2 (acceleration cannot be calculated).
|
—
|
—
|
—
|
—
|
|
Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
>= 30% heart rate increase, SDA 6 (n=8; N=4))
|
100 percentage of True Positive Detections
Confidence interval not computable where the mean sensitivity equals to 100%, or where number of patients within the setting is less than or equal to 2 (acceleration cannot be calculated).
|
—
|
—
|
—
|
—
|
|
Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
>= 20% heart rate increase, SDA 6 (n=12; N=5)
|
100 percentage of True Positive Detections
Confidence interval not computable where the mean sensitivity equals to 100%, or where number of patients within the setting is less than or equal to 2 (acceleration cannot be calculated).
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Epilepsy Monitoring Unit (EMU) StayPopulation: Patients from the ITT population who completed the EMU evaluation and that had at least one reported seizure during the EMU evaluation that was confirmed by triple review; (Investigator Reported Seizures + Triple Review).
Sensitivity is defined as the total number of seizures detected divided by the total number of seizures during the EMU stay. Data used to support sensitivity analyses included digital ECG/EEG files, corresponding M106 device downloads, and CRF data. Seizure onset times were compared with modeled M106 device detections at the least sensitive setting capable of detecting the seizure based on the corresponding change in heart rate. The participants' surface ECG data collected during the trial and passed through DMSDAT, a validated bench-top simulant of the Automatic Stimulation feature, was used to produce modeled results for each threshold for AutoStim setting (1;70%, 2;60%, 3;50%, 4;40%, 5;30% and 6;20%). Number of participants is total number of subjects who experienced seizures during the EMU stay. Bootstrap confidence intervals using 3000 bootstrap samples.
Outcome measures
| Measure |
Reported by Investigators
n=18 Participants
All seizures that occurred during EMU stay and that were identified by investigators.
|
Reported by Triple Review
All seizures that occurred during EMU stay and that were identified by triple review post EMU.
|
Total
Seizures from an ITT subject that were either identified by the investigator during EMU evaluation or during the triple review process of EEG data.
|
Generalized Tonic Clonic Sz
NHS3 Scores at Follow-Up Visits
|
SSQ Scores at 24 Months
Change From Baseline at Each Category
|
|---|---|---|---|---|---|
|
Modeled Sensitivity Based on Heart Rate Increase Associated With Seizures by SDA Setting Post-Processed Through Bench-top Device Simulant
>= 70% heart rate increase at SDA 1 (n=5)
|
100 percentage of True Positive Detections
Confidence interval left blank where the mean sensitivity equals to 100%
|
—
|
—
|
—
|
—
|
|
Modeled Sensitivity Based on Heart Rate Increase Associated With Seizures by SDA Setting Post-Processed Through Bench-top Device Simulant
>= 60% heart rate increase at SDA 2 (n=7)
|
85.7 percentage of True Positive Detections
Interval 70.0 to 100.0
|
—
|
—
|
—
|
—
|
|
Modeled Sensitivity Based on Heart Rate Increase Associated With Seizures by SDA Setting Post-Processed Through Bench-top Device Simulant
>= 50% heart rate increase at SDA 3 (n=11)
|
81.8 percentage of True Positive Detections
Interval 57.14 to 100.0
|
—
|
—
|
—
|
—
|
|
Modeled Sensitivity Based on Heart Rate Increase Associated With Seizures by SDA Setting Post-Processed Through Bench-top Device Simulant
>= 40% heart rate increase at SDA 4 (n=19)
|
89.5 percentage of True Positive Detections
Interval 73.68 to 100.0
|
—
|
—
|
—
|
—
|
|
Modeled Sensitivity Based on Heart Rate Increase Associated With Seizures by SDA Setting Post-Processed Through Bench-top Device Simulant
>= 30% heart rate increase at SDA 5 (n=36)
|
88.9 percentage of True Positive Detections
Interval 76.67 to 97.37
|
—
|
—
|
—
|
—
|
|
Modeled Sensitivity Based on Heart Rate Increase Associated With Seizures by SDA Setting Post-Processed Through Bench-top Device Simulant
>= 20% heart rate increase at SDA 6 (n=53)
|
92.5 percentage of True Positive Detections
Interval 79.66 to 100.0
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Epilepsy Monitoring Unit (EMU) StayPopulation: ITT Population: all patients implanted with Model 106 VNS Therapy System Version 2 and who have any EMU record. 10 participants analyzed for \>=60% setting, 12 participants analyzed for \>=40% setting, 8 participants analyzed for \>=20% setting.
Potential false positive rate is defined as the sum across all patients of the total number of potential false positive detections divided by the sum across all patients of the appropriate monitoring time during the EMU stay. Data used to support the potential false positive rate analyses included digital ECG/EEG files retrieved from the EMU evaluation, corresponding M106 device downloads, and triple review results of EEG recordings. The evaluated EMU monitoring time includes a daily 3 minutes stepping exercise during which patients stepped up and down on a step stool at a submaximal effort leve.
Outcome measures
| Measure |
Reported by Investigators
n=30 Participants
All seizures that occurred during EMU stay and that were identified by investigators.
|
Reported by Triple Review
All seizures that occurred during EMU stay and that were identified by triple review post EMU.
|
Total
Seizures from an ITT subject that were either identified by the investigator during EMU evaluation or during the triple review process of EEG data.
|
Generalized Tonic Clonic Sz
NHS3 Scores at Follow-Up Visits
|
SSQ Scores at 24 Months
Change From Baseline at Each Category
|
|---|---|---|---|---|---|
|
Potential False Positives Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
>=60%, SDA 2
|
0.5 Potential False Positive per Hour
Interval 0.2 to 0.96
|
—
|
—
|
—
|
—
|
|
Potential False Positives Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
>=40%, SDA 4
|
2.7 Potential False Positive per Hour
Interval 1.7 to 3.91
|
—
|
—
|
—
|
—
|
|
Potential False Positives Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
>=20%, SDA 6
|
7.2 Potential False Positive per Hour
Interval 5.31 to 9.94
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At Implant, First Titration Visit, Day 1 EMU and 12 MonthsPopulation: ITT population
Cardiac R-wave detection was evaluated against concurrent ECG data (i.e. detailed R-wave test) collected during implant, the first titration visit, at the beginning of the EMU stay, and at the 12 month visit. R-R intervals were calculated using detected R-waves from the Implantable Pulse Generator (IPG) and from a standard ECG monitor during a pre-specified time interval. A time series 10 seconds was recorded using the IPG SyncPulse feature. Simultaneously, a corresponding time series over the same interval was recorded using a standard ECG monitor. The total number of beats accurately detected in the entire study population is reported.
Outcome measures
| Measure |
Reported by Investigators
n=30 Participants
All seizures that occurred during EMU stay and that were identified by investigators.
|
Reported by Triple Review
All seizures that occurred during EMU stay and that were identified by triple review post EMU.
|
Total
Seizures from an ITT subject that were either identified by the investigator during EMU evaluation or during the triple review process of EEG data.
|
Generalized Tonic Clonic Sz
NHS3 Scores at Follow-Up Visits
|
SSQ Scores at 24 Months
Change From Baseline at Each Category
|
|---|---|---|---|---|---|
|
Validation of Cardiac R-Wave Detection
At Implant (n=26)
|
95.52 percentage of beats accurately detected
|
—
|
—
|
—
|
—
|
|
Validation of Cardiac R-Wave Detection
First Titration Visit (n=19)
|
98.74 percentage of beats accurately detected
|
—
|
—
|
—
|
—
|
|
Validation of Cardiac R-Wave Detection
EMU Day 1 (n=29)
|
99.71 percentage of beats accurately detected
|
—
|
—
|
—
|
—
|
|
Validation of Cardiac R-Wave Detection
12 Month Follow-up (n=14)
|
99.43 percentage of beats accurately detected
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Epilepsy Monitoring Unit (EMU) StayPopulation: ITT Population n=total number of seizures in each category
Latency is defined as the time difference between SDA detection time and the annotated seizure onset time. The earliest SDA detection was considered for each seizure. Seizure onset times were compared with M106 device detections at the randomized SDA setting. Negative latencies indicate that the SDA detection preceded the seizure onset time. The median latency is presented for seizures which met the definition of ictal tachycardia as well as all seizure types and indicate the observed latency range.
Outcome measures
| Measure |
Reported by Investigators
n=30 Participants
All seizures that occurred during EMU stay and that were identified by investigators.
|
Reported by Triple Review
n=30 Participants
All seizures that occurred during EMU stay and that were identified by triple review post EMU.
|
Total
Seizures from an ITT subject that were either identified by the investigator during EMU evaluation or during the triple review process of EEG data.
|
Generalized Tonic Clonic Sz
NHS3 Scores at Follow-Up Visits
|
SSQ Scores at 24 Months
Change From Baseline at Each Category
|
|---|---|---|---|---|---|
|
Characterization of Latency Period: Analysis of Observed Latency for True Positive Detections by Randomized SDA Setting
SDA 2 (n=1, 8)
|
4 seconds
Interval 4.0 to 4.0
|
19.5 seconds
Interval -89.0 to 92.0
|
—
|
—
|
—
|
|
Characterization of Latency Period: Analysis of Observed Latency for True Positive Detections by Randomized SDA Setting
SDA 4 (n=6,8)
|
27.5 seconds
Interval 12.0 to 57.0
|
27.5 seconds
Interval 0.0 to 57.0
|
—
|
—
|
—
|
|
Characterization of Latency Period: Analysis of Observed Latency for True Positive Detections by Randomized SDA Setting
SDA 6 (n=2,37)
|
-14.5 seconds
Interval -42.0 to 13.0
|
7 seconds
Interval -112.0 to 110.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: At implant/recovery up to EMU Discharge (2 to 4 weeks)Population: ITT Population
Usability survey data were collected from all site personnel who used the handheld programmer to evaluate the usability of the AspireSR® VNS Therapy® System.The device usability survey contained 17 questions that measure usability on a five-point Likert scale ranging from "Extremely Difficult" (5) to "Extremely Easy" (1). Site personnel were asked to assess usability of the software features, instructions for use, training materials, and overall usability of the system at four different time points. The time points include implant/recovery and the end of EMU. Usability was calculated as percentage of the users who found the usability of system to be "easy-2" or extremely easy-1".
Outcome measures
| Measure |
Reported by Investigators
n=30 Participants
All seizures that occurred during EMU stay and that were identified by investigators.
|
Reported by Triple Review
n=30 Participants
All seizures that occurred during EMU stay and that were identified by triple review post EMU.
|
Total
Seizures from an ITT subject that were either identified by the investigator during EMU evaluation or during the triple review process of EEG data.
|
Generalized Tonic Clonic Sz
NHS3 Scores at Follow-Up Visits
|
SSQ Scores at 24 Months
Change From Baseline at Each Category
|
|---|---|---|---|---|---|
|
Human Factors and Usability of the AspireSR® VNS Therapy® System.
Training Material (n=21, 23)
|
76.2 Percentage of participants rated 1 or 2
|
73.9 Percentage of participants rated 1 or 2
|
—
|
—
|
—
|
|
Human Factors and Usability of the AspireSR® VNS Therapy® System.
Physician's Manual (n=18, 20)
|
61.1 Percentage of participants rated 1 or 2
|
70.0 Percentage of participants rated 1 or 2
|
—
|
—
|
—
|
|
Human Factors and Usability of the AspireSR® VNS Therapy® System.
Laminated Instruction Card (n=20, 21)
|
75.0 Percentage of participants rated 1 or 2
|
81.0 Percentage of participants rated 1 or 2
|
—
|
—
|
—
|
|
Human Factors and Usability of the AspireSR® VNS Therapy® System.
Interrogation (Short) (n=22, 24)
|
86.4 Percentage of participants rated 1 or 2
|
91.7 Percentage of participants rated 1 or 2
|
—
|
—
|
—
|
|
Human Factors and Usability of the AspireSR® VNS Therapy® System.
Interrogation (Long) (n=21, 24)
|
57.1 Percentage of participants rated 1 or 2
|
83.3 Percentage of participants rated 1 or 2
|
—
|
—
|
—
|
|
Human Factors and Usability of the AspireSR® VNS Therapy® System.
Change Parameters (n=22, 24)
|
90.9 Percentage of participants rated 1 or 2
|
95.8 Percentage of participants rated 1 or 2
|
—
|
—
|
—
|
|
Human Factors and Usability of the AspireSR® VNS Therapy® System.
Heartbeat Sensitivity Configuration (n=20, 24)
|
80.0 Percentage of participants rated 1 or 2
|
83.3 Percentage of participants rated 1 or 2
|
—
|
—
|
—
|
|
Human Factors and Usability of the AspireSR® VNS Therapy® System.
Seizure Detection Configuration (n=21, 23)
|
81.0 Percentage of participants rated 1 or 2
|
82.6 Percentage of participants rated 1 or 2
|
—
|
—
|
—
|
|
Human Factors and Usability of the AspireSR® VNS Therapy® System.
System Diagnostic (n=21,24)
|
85.7 Percentage of participants rated 1 or 2
|
87.5 Percentage of participants rated 1 or 2
|
—
|
—
|
—
|
|
Human Factors and Usability of the AspireSR® VNS Therapy® System.
View Database (n=17, 22)
|
58.8 Percentage of participants rated 1 or 2
|
72.7 Percentage of participants rated 1 or 2
|
—
|
—
|
—
|
|
Human Factors and Usability of the AspireSR® VNS Therapy® System.
View Seizure Detection Data (n=15, 22)
|
66.7 Percentage of participants rated 1 or 2
|
63.6 Percentage of participants rated 1 or 2
|
—
|
—
|
—
|
|
Human Factors and Usability of the AspireSR® VNS Therapy® System.
Export Data (n=7, 15)
|
100 Percentage of participants rated 1 or 2
|
66.7 Percentage of participants rated 1 or 2
|
—
|
—
|
—
|
|
Human Factors and Usability of the AspireSR® VNS Therapy® System.
Generator Battery Status Indicators (n=20, 24)
|
70.0 Percentage of participants rated 1 or 2
|
87.5 Percentage of participants rated 1 or 2
|
—
|
—
|
—
|
|
Human Factors and Usability of the AspireSR® VNS Therapy® System.
Handheld Battery Status Indicator (n=19, 24)
|
68.4 Percentage of participants rated 1 or 2
|
83.3 Percentage of participants rated 1 or 2
|
—
|
—
|
—
|
|
Human Factors and Usability of the AspireSR® VNS Therapy® System.
Warning Messages (n=13, 24)
|
84.6 Percentage of participants rated 1 or 2
|
87.5 Percentage of participants rated 1 or 2
|
—
|
—
|
—
|
|
Human Factors and Usability of the AspireSR® VNS Therapy® System.
Overall Usability (n=20, 24)
|
80.0 Percentage of participants rated 1 or 2
|
70.8 Percentage of participants rated 1 or 2
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 24 Month visitPopulation: ITT population
Seizure frequency was calculated at 3, 6, 12, 18 and 24 month follow-up visits based on seizure diary information and compared to baseline estimates. Response rate was computed and summarized for partial seizures (SPS, CPS and CPS with 2nd GTCs) and overall seizure types as the percentage of patients that achieved ≥50% seizure reduction per month from baseline by visit.
Outcome measures
| Measure |
Reported by Investigators
n=30 Participants
All seizures that occurred during EMU stay and that were identified by investigators.
|
Reported by Triple Review
n=30 Participants
All seizures that occurred during EMU stay and that were identified by triple review post EMU.
|
Total
Seizures from an ITT subject that were either identified by the investigator during EMU evaluation or during the triple review process of EEG data.
|
Generalized Tonic Clonic Sz
NHS3 Scores at Follow-Up Visits
|
SSQ Scores at 24 Months
Change From Baseline at Each Category
|
|---|---|---|---|---|---|
|
Changes From Baseline in Seizure Frequency
Follow-up 3 Month n=29,27
|
24.1 Percentage of participants
Interval 10.3 to 43.54
|
25.9 Percentage of participants
Interval 11.11 to 46.28
|
—
|
—
|
—
|
|
Changes From Baseline in Seizure Frequency
Follow-up 6 Month n=30,28
|
20.0 Percentage of participants
Interval 7.71 to 38.57
|
25 Percentage of participants
Interval 10.69 to 44.87
|
—
|
—
|
—
|
|
Changes From Baseline in Seizure Frequency
Follow-up 12 Month n=27,25
|
33.3 Percentage of participants
Interval 16.52 to 53.96
|
36.0 Percentage of participants
Interval 17.97 to 57.48
|
—
|
—
|
—
|
|
Changes From Baseline in Seizure Frequency
Follow-up 18 Month n=26,24
|
34.6 Percentage of participants
Interval 17.21 to 55.67
|
37.5 Percentage of participants
Interval 18.8 to 59.41
|
—
|
—
|
—
|
|
Changes From Baseline in Seizure Frequency
Follow-up 24 Month n=27,25
|
33.3 Percentage of participants
Interval 16.52 to 53.96
|
36.0 Percentage of participants
Interval 17.97 to 57.48
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 24 Months VisitPopulation: ITT Population
Investigators completed the National Hospital Seizure Severity Scale (NHS3) questionnaire at screening, at the end of the EMU stay (provided a seizure occurred during the EMU stay), and at follow-up visits. Severity was evaluated by seizure type. The range of NHS3 scale is 1-27 with 1 being the least severe and 27 being the most severe. Negative median value means improvement.
Outcome measures
| Measure |
Reported by Investigators
n=30 Participants
All seizures that occurred during EMU stay and that were identified by investigators.
|
Reported by Triple Review
n=30 Participants
All seizures that occurred during EMU stay and that were identified by triple review post EMU.
|
Total
n=30 Participants
Seizures from an ITT subject that were either identified by the investigator during EMU evaluation or during the triple review process of EEG data.
|
Generalized Tonic Clonic Sz
n=30 Participants
NHS3 Scores at Follow-Up Visits
|
SSQ Scores at 24 Months
Change From Baseline at Each Category
|
|---|---|---|---|---|---|
|
Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3)
Baseline to EMU Discharge; n=11,19,5,3
|
0.00 Units on a scale
Interval -4.0 to 1.0
|
-1.00 Units on a scale
Interval -10.0 to 0.0
|
0.00 Units on a scale
Interval -14.0 to 0.0
|
-4.00 Units on a scale
Interval -5.0 to 0.0
|
—
|
|
Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3)
Baseline to 3 Months; n=12,20,6,2
|
0.00 Units on a scale
Interval -6.0 to 2.0
|
-1.00 Units on a scale
Interval -8.0 to 3.0
|
0.00 Units on a scale
Interval -10.0 to 1.0
|
-6.50 Units on a scale
Interval -13.0 to 0.0
|
—
|
|
Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3)
Baseline to 6 Months; n=9,20,5,3
|
0.00 Units on a scale
Interval -2.0 to 9.0
|
-1.33 Units on a scale
Interval -9.0 to 3.2
|
0.00 Units on a scale
Interval -14.0 to 0.0
|
0.00 Units on a scale
Interval -12.0 to 9.0
|
—
|
|
Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3)
Baseline to 12 Months; n=9,20,6,5
|
0.00 Units on a scale
Interval -4.0 to 4.0
|
-1.83 Units on a scale
Interval -8.0 to 3.2
|
0.00 Units on a scale
Interval -10.0 to 1.0
|
-8.00 Units on a scale
Interval -10.0 to 0.0
|
—
|
|
Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3)
Baseline to 18 Months; n=7,20,7,3
|
2.00 Units on a scale
Interval -3.0 to 6.0
|
-1.50 Units on a scale
Interval -12.0 to 5.0
|
-1.0 Units on a scale
Interval -8.0 to 1.0
|
-7.00 Units on a scale
Interval -10.0 to 0.0
|
—
|
|
Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3)
Baseline to 24 Months; n=8,20,2,2
|
-0.50 Units on a scale
Interval -4.0 to 10.0
|
-2.00 Units on a scale
Interval -12.0 to 5.0
|
-2.00 Units on a scale
Interval -3.0 to -1.0
|
-8.00 Units on a scale
Interval -10.0 to -6.0
|
—
|
SECONDARY outcome
Timeframe: Up to 24 Month visitPopulation: ITT Population
Clinical outcomes such as seizure severity, intensity and post-ictal duration were also assessed during the long-term follow-up visits (3, 6, 12, 18 and 24 months) with patient reported questionnaires (SSQ; Seizure Severity Questionnaire). The range for SSQ (all sub-scores) is 1-7 with 1 being the least severe and 7 being the most severe. Mean SSQ scores at 3, 6, 12, 18 and 24 months were compared to baseline. A change from baseline is calculated as baseline minus follow-up visit score to correspond to the Minimally Important Change (MIC) criteria as defined in the Scoring Scheme for SSQ v2. Questionnaire. Subscale scores were averaged to compute the SSQ Total Score
Outcome measures
| Measure |
Reported by Investigators
n=30 Participants
All seizures that occurred during EMU stay and that were identified by investigators.
|
Reported by Triple Review
n=30 Participants
All seizures that occurred during EMU stay and that were identified by triple review post EMU.
|
Total
n=30 Participants
Seizures from an ITT subject that were either identified by the investigator during EMU evaluation or during the triple review process of EEG data.
|
Generalized Tonic Clonic Sz
n=30 Participants
NHS3 Scores at Follow-Up Visits
|
SSQ Scores at 24 Months
n=30 Participants
Change From Baseline at Each Category
|
|---|---|---|---|---|---|
|
Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Seizure Severity Questionnaire (SSQ)
SSQ Total Score n=24,27,26,23,20 MIC=0.48
|
0.516 Units on a scale
Standard Deviation 1.688
|
0.728 Units on a scale
Standard Deviation 1.567
|
0.354 Units on a scale
Standard Deviation 1.640
|
0.341 Units on a scale
Standard Deviation 1.461
|
0.966 Units on a scale
Standard Deviation 1.975
|
|
Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Seizure Severity Questionnaire (SSQ)
Activity During Seizure; n=26,28,27,25,22 MIC=0.50
|
1.115 Units on a scale
Standard Deviation 2.783
|
1.643 Units on a scale
Standard Deviation 2.714
|
0.907 Units on a scale
Standard Deviation 2.557
|
0.800 Units on a scale
Standard Deviation 2.441
|
1.818 Units on a scale
Standard Deviation 2.982
|
|
Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Seizure Severity Questionnaire (SSQ)
Overall Recovery; n=25,29,27,27,26 MIC=0.39
|
0.627 Units on a scale
Standard Deviation 3.101
|
0.663 Units on a scale
Standard Deviation 2.125
|
0.481 Units on a scale
Standard Deviation 2.514
|
0.280 Units on a scale
Standard Deviation 2.913
|
0.218 Units on a scale
Standard Deviation 2.783
|
|
Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Seizure Severity Questionnaire (SSQ)
Overall Severity; n=27,30,29,28,27 MIC=0.48
|
0.519 Units on a scale
Standard Deviation 3.022
|
0.589 Units on a scale
Standard Deviation 2.097
|
0.425 Units on a scale
Standard Deviation 2.486
|
0.131 Units on a scale
Standard Deviation 2.855
|
0.160 Units on a scale
Standard Deviation 2.806
|
|
Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Seizure Severity Questionnaire (SSQ)
Postictal Emotional Rec. n=26,29,28,27,26 MIC=0.42
|
0.397 Units on a scale
Standard Deviation 3.281
|
0.805 Units on a scale
Standard Deviation 2.832
|
0.179 Units on a scale
Standard Deviation 3.093
|
-0.062 Units on a scale
Standard Deviation 3.480
|
0.359 Units on a scale
Standard Deviation 3.124
|
|
Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Seizure Severity Questionnaire (SSQ)
Postictal Physical Reco; n=27,30,28,28,27 MIC=0.34
|
0.975 Units on a scale
Standard Deviation 3.375
|
0.567 Units on a scale
Standard Deviation 2.208
|
0.393 Units on a scale
Standard Deviation 3.012
|
0.476 Units on a scale
Standard Deviation 3.018
|
0.012 Units on a scale
Standard Deviation 3.043
|
|
Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Seizure Severity Questionnaire (SSQ)
Postictal Cognitive Rec.;n=28,30,29,28,27 MIC=0.48
|
0.536 Units on a scale
Standard Deviation 3.467
|
0.578 Units on a scale
Standard Deviation 2.946
|
0.805 Units on a scale
Standard Deviation 2.814
|
0.274 Units on a scale
Standard Deviation 3.587
|
0.099 Units on a scale
Standard Deviation 3.404
|
SECONDARY outcome
Timeframe: Epilepsy Monitoring Unit (EMU) StayPopulation: ITT Population; All Treated Seizures n=total number of seizures
Clinical outcomes including seizure duration and cessation were assessed with vEEG during EMU stay. Number of seizures treated with Automatic Stimulation during EMU were evaluated. Of these seizures, those ending during the 60 second course of Automatic Stimulation were assessed and tabulated by seizure type.
Outcome measures
| Measure |
Reported by Investigators
n=30 Participants
All seizures that occurred during EMU stay and that were identified by investigators.
|
Reported by Triple Review
All seizures that occurred during EMU stay and that were identified by triple review post EMU.
|
Total
Seizures from an ITT subject that were either identified by the investigator during EMU evaluation or during the triple review process of EEG data.
|
Generalized Tonic Clonic Sz
NHS3 Scores at Follow-Up Visits
|
SSQ Scores at 24 Months
Change From Baseline at Each Category
|
|---|---|---|---|---|---|
|
Proportion of Seizures Ending During Stimulation by Type
Overall (n=33)
|
57.6 Percentage of Seizures Ending
|
—
|
—
|
—
|
—
|
|
Proportion of Seizures Ending During Stimulation by Type
Partial Seizures (not otherwise specified) (n=5)
|
20 Percentage of Seizures Ending
|
—
|
—
|
—
|
—
|
|
Proportion of Seizures Ending During Stimulation by Type
Simple Partial Seizures (n=4)
|
100 Percentage of Seizures Ending
|
—
|
—
|
—
|
—
|
|
Proportion of Seizures Ending During Stimulation by Type
Complex Partial Seizures (n=11)
|
54.5 Percentage of Seizures Ending
|
—
|
—
|
—
|
—
|
|
Proportion of Seizures Ending During Stimulation by Type
Secondary Generalized Seizures (n=2)
|
0.0 Percentage of Seizures Ending
|
—
|
—
|
—
|
—
|
|
Proportion of Seizures Ending During Stimulation by Type
Generalized Seizures (n=9)
|
66.7 Percentage of Seizures Ending
|
—
|
—
|
—
|
—
|
|
Proportion of Seizures Ending During Stimulation by Type
Debilitating Seizures (CPS, SGS, GEN) (n=22)
|
54.5 Percentage of Seizures Ending
|
—
|
—
|
—
|
—
|
|
Proportion of Seizures Ending During Stimulation by Type
Unknown Type (n=2)
|
100 Percentage of Seizures Ending
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Historical Seizures and Seizures during Epilepsy Monitoring Unit StayPopulation: Patients from the ITT population who had at least one seizure during the EMU stay and who had at least one historical seizure recorded (and duration was annotated). n=total number of seizures
Seizure duration was calculated using historical EEG data from patients enrolled in the trial and compared to the duration of seizures that occurred during the study EMU stay. The seizure start and end times were determined via clinical observation and/or through an adjudication process with qualified EEG reviewers.
Outcome measures
| Measure |
Reported by Investigators
n=30 Participants
All seizures that occurred during EMU stay and that were identified by investigators.
|
Reported by Triple Review
n=30 Participants
All seizures that occurred during EMU stay and that were identified by triple review post EMU.
|
Total
n=30 Participants
Seizures from an ITT subject that were either identified by the investigator during EMU evaluation or during the triple review process of EEG data.
|
Generalized Tonic Clonic Sz
NHS3 Scores at Follow-Up Visits
|
SSQ Scores at 24 Months
Change From Baseline at Each Category
|
|---|---|---|---|---|---|
|
Summary of Seizure Duration (Seconds) for All Seizure Types by Subgroup(ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated)
Simple Partial Seizures n=6,4,0
|
45.5 Seconds
Standard Deviation 28.9
|
40.5 Seconds
Standard Deviation 32.1
|
NA Seconds
Standard Deviation NA
no seizures reported
|
—
|
—
|
|
Summary of Seizure Duration (Seconds) for All Seizure Types by Subgroup(ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated)
Complex Partial Seizures n=60,6,7
|
150.2 Seconds
Standard Deviation 461.5
|
26.8 Seconds
Standard Deviation 16.2
|
150.7 Seconds
Standard Deviation 153.6
|
—
|
—
|
|
Summary of Seizure Duration (Seconds) for All Seizure Types by Subgroup(ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated)
CPS Secondary Generalized n=12,0,0
|
107.3 Seconds
Standard Deviation 49.3
|
NA Seconds
Standard Deviation NA
no seizures reported
|
NA Seconds
Standard Deviation NA
no seizures reported
|
—
|
—
|
|
Summary of Seizure Duration (Seconds) for All Seizure Types by Subgroup(ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated)
Generalized Seizures n=0,6,0
|
NA Seconds
Standard Deviation NA
no seizures reported
|
20.3 Seconds
Standard Deviation 10.4
|
NA Seconds
Standard Deviation NA
no seizures reported
|
—
|
—
|
|
Summary of Seizure Duration (Seconds) for All Seizure Types by Subgroup(ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated)
Debilitating Seizures n=72,12,7
|
143.1 Seconds
Standard Deviation 421.5
|
23.6 Seconds
Standard Deviation 13.4
|
150.7 Seconds
Standard Deviation 153.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Historical Seizures and Seizures during Epilepsy Monitoring Unit StayPopulation: Patients from the ITT population who had at least one seizure during the EMU stay and who had at least one historical seizure recorded (and duration was annotated). n=total number of seizures
Post-ictal duration was quantified by identifying the time at which the number of EEG channels within the 95% confidence interval of relative power reaches a number that is consistent with that during the pre-seizure period. This measure represents the amount of time required following a seizure until the EEG recovers to the pre-seizure state. It is used to objectively estimate patient recovery time. Historical seizures were baseline EEG recordings measured during monitoring prior to implantation. Post-ictal duration is only reported for seizures with Post Ictal Duration (seconds) annotated and \>= 20% Heart Rate Rise
Outcome measures
| Measure |
Reported by Investigators
n=30 Participants
All seizures that occurred during EMU stay and that were identified by investigators.
|
Reported by Triple Review
n=30 Participants
All seizures that occurred during EMU stay and that were identified by triple review post EMU.
|
Total
n=30 Participants
Seizures from an ITT subject that were either identified by the investigator during EMU evaluation or during the triple review process of EEG data.
|
Generalized Tonic Clonic Sz
NHS3 Scores at Follow-Up Visits
|
SSQ Scores at 24 Months
Change From Baseline at Each Category
|
|---|---|---|---|---|---|
|
Summary of Post Ictal Duration (Seconds) for All Seizure Types (ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated)
Simple Partial Seizures n=5,4,0
|
274.6 Seconds
Standard Deviation 349.9
|
102.8 Seconds
Standard Deviation 110.2
|
NA Seconds
Standard Deviation NA
No seizures recorded
|
—
|
—
|
|
Summary of Post Ictal Duration (Seconds) for All Seizure Types (ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated)
Complex Partial Seizures n=59,6,7
|
44.1 Seconds
Standard Deviation 67.3
|
85.7 Seconds
Standard Deviation 81.7
|
66.6 Seconds
Standard Deviation 99.9
|
—
|
—
|
|
Summary of Post Ictal Duration (Seconds) for All Seizure Types (ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated)
CPS Secondary Generalized n=5,0,0
|
258.2 Seconds
Standard Deviation 199.3
|
NA Seconds
Standard Deviation NA
No seizures recorded
|
NA Seconds
Standard Deviation NA
No seizures recorded
|
—
|
—
|
|
Summary of Post Ictal Duration (Seconds) for All Seizure Types (ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated)
Generalized Seizures n=0,1,0
|
NA Seconds
Standard Deviation NA
No pre-study seizures (historical seizures) provided
|
9.4 Seconds
Standard Deviation 0.0
|
NA Seconds
Standard Deviation NA
No seizures recorded
|
—
|
—
|
|
Summary of Post Ictal Duration (Seconds) for All Seizure Types (ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated)
Debilitating Seizures n=64,7,7
|
60.9 Seconds
Standard Deviation 100.2
|
74.8 Seconds
Standard Deviation 79.9
|
66.6 Seconds
Standard Deviation 99.9
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 24 Months VisitPopulation: ITT Population
Quality of life data was collected using patient-completed QOLIE-31-P surveys and compared between baseline and follow-up visits. The MIC score for each subscale defines the threshold for Minimally Important Change. If a score exceeds the MIC Score, the improvement from baseline is considered clinically significant. The range for QOLIE-31-P (all sub-scores) is 0-100 with higher scores reflecting greater well-being.Subscale scores were averaged to compute the QOLIE Total Score.
Outcome measures
| Measure |
Reported by Investigators
n=30 Participants
All seizures that occurred during EMU stay and that were identified by investigators.
|
Reported by Triple Review
n=30 Participants
All seizures that occurred during EMU stay and that were identified by triple review post EMU.
|
Total
n=30 Participants
Seizures from an ITT subject that were either identified by the investigator during EMU evaluation or during the triple review process of EEG data.
|
Generalized Tonic Clonic Sz
n=30 Participants
NHS3 Scores at Follow-Up Visits
|
SSQ Scores at 24 Months
n=30 Participants
Change From Baseline at Each Category
|
|---|---|---|---|---|---|
|
Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P)
QOLIE Overall Total (MIC=5.19) n=28,29,28,28,26
|
3.7 units on a scale
Standard Deviation 16.6
|
4.4 units on a scale
Standard Deviation 18.7
|
8.9 units on a scale
Standard Deviation 18.4
|
10.2 units on a scale
Standard Deviation 15.9
|
8.7 units on a scale
Standard Deviation 25.3
|
|
Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P)
Energy/Fatigue (MIC=5.25) n=28,29,28,28,25
|
2.3 units on a scale
Standard Deviation 17.6
|
-2.3 units on a scale
Standard Deviation 17.9
|
4.3 units on a scale
Standard Deviation 23.9
|
4.9 units on a scale
Standard Deviation 21.0
|
6.9 units on a scale
Standard Deviation 23.6
|
|
Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P)
Emotional Well Being (MIC=4.76) n=28,29,28,28,26
|
0.4 units on a scale
Standard Deviation 25.1
|
-1.9 units on a scale
Standard Deviation 21.4
|
7.1 units on a scale
Standard Deviation 23.9
|
9.2 units on a scale
Standard Deviation 24.7
|
8.2 units on a scale
Standard Deviation 25.5
|
|
Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P)
Social Functioning (MIC=3.95) n=27,28,26,27,26
|
11.7 units on a scale
Standard Deviation 25.8
|
11.6 units on a scale
Standard Deviation 26.3
|
20.1 units on a scale
Standard Deviation 30.9
|
14.6 units on a scale
Standard Deviation 18.6
|
10.2 units on a scale
Standard Deviation 27.7
|
|
Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P)
Cognitive functioning (MIC=5.34) n=28,29,28,27,26
|
1.3 units on a scale
Standard Deviation 27.7
|
12.4 units on a scale
Standard Deviation 37.7
|
8.4 units on a scale
Standard Deviation 30.3
|
13.6 units on a scale
Standard Deviation 30.4
|
9.6 units on a scale
Standard Deviation 39.2
|
|
Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P)
Medication Effects (MIC=5.00) n=28,29,28,26,26
|
4.5 units on a scale
Standard Deviation 35.9
|
3.3 units on a scale
Standard Deviation 27.5
|
0.9 units on a scale
Standard Deviation 21.4
|
5.7 units on a scale
Standard Deviation 31.1
|
1.1 units on a scale
Standard Deviation 40.1
|
|
Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P)
Seizure Worry (MIC=7.42) n=28,29,28,28,26
|
2.8 units on a scale
Standard Deviation 26.6
|
2.1 units on a scale
Standard Deviation 24.4
|
7.7 units on a scale
Standard Deviation 27.9
|
8.1 units on a scale
Standard Deviation 18.9
|
7.5 units on a scale
Standard Deviation 31.0
|
|
Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P)
Overall Quality of Life (MIC=6.42)n=28,29,28,28,26
|
3.7 units on a scale
Standard Deviation 25.9
|
6.2 units on a scale
Standard Deviation 25.4
|
14.9 units on a scale
Standard Deviation 24.7
|
15.0 units on a scale
Standard Deviation 23.1
|
16.0 units on a scale
Standard Deviation 31.2
|
SECONDARY outcome
Timeframe: Historical Seizures and Seizures during Epilepsy Monitoing Unit StayPopulation: Patients from the ITT population who had at least one seizure during EMU stay and who had at least one historical seizure recorded. n=total number of seizures
Quantitative evaluation of EEG was used to characterize the seizures that were treated with Automatic Stimulation. Intensity was evaluated by surveying the average power level from the 10-20 system EEG channel of maximum output during the course of the seizure. Intensity was only reported for seizures with intensity annotated and \>= 20% Heart Rate Rise. The relative intensity was calculated by normalizing the power calculations to the pre-seizure state, and thus the reported changes are dimensionless. n= number of seizures
Outcome measures
| Measure |
Reported by Investigators
n=30 Participants
All seizures that occurred during EMU stay and that were identified by investigators.
|
Reported by Triple Review
n=30 Participants
All seizures that occurred during EMU stay and that were identified by triple review post EMU.
|
Total
n=30 Participants
Seizures from an ITT subject that were either identified by the investigator during EMU evaluation or during the triple review process of EEG data.
|
Generalized Tonic Clonic Sz
n=30 Participants
NHS3 Scores at Follow-Up Visits
|
SSQ Scores at 24 Months
Change From Baseline at Each Category
|
|---|---|---|---|---|---|
|
Overall Summary of Seizure Intensity by Subgroup
Simple Partial Seizures n=6, 8, 4, 0
|
33.9 unitless
Standard Deviation 33.9
|
225.3 unitless
Standard Deviation 427.1
|
406.6 unitless
Standard Deviation 581.0
|
NA unitless
Standard Deviation NA
no seizures recorded
|
—
|
|
Overall Summary of Seizure Intensity by Subgroup
Complex Partial Seizures n=60, 9, 6, 7
|
205.4 unitless
Standard Deviation 519.2
|
989.4 unitless
Standard Deviation 2307.0
|
59.5 unitless
Standard Deviation 65.2
|
51.6 unitless
Standard Deviation 74.7
|
—
|
|
Overall Summary of Seizure Intensity by Subgroup
CPS Secondary generalized n=10, 2, 0, 0
|
435.1 unitless
Standard Deviation 654.7
|
611.4 unitless
Standard Deviation 832.2
|
NA unitless
Standard Deviation NA
no seizures recorded
|
NA unitless
Standard Deviation NA
no seizures recorded
|
—
|
|
Overall Summary of Seizure Intensity by Subgroup
Debilitating Seizures n=70, 12, 7, 7
|
238.2 unitless
Standard Deviation 541.2
|
852.1 unitless
Standard Deviation 2002.8
|
65.0 unitless
Standard Deviation 61.3
|
51.6 unitless
Standard Deviation 74.7
|
—
|
SECONDARY outcome
Timeframe: EMU stayPopulation: ITT population
During a 1 hour period during the EMU stay, the VNS Therapy device was programmed to normal mode stimulation ON time 30 seconds, OFF time 5 minutes. AutoStim and Magnet Mode were programmed OFF. In this hour, 10 to 11 normal mode stimulations can be expected. Around each of these stimulations, ECG data were collected to assess potential stimulation related heart rate changes (during stimulation, after stimulation and after black-out time). A black-out time is a period after stimulation during which no seizure detections can occur, to ensure that potential stimulation related heart rate changes were not seen as ictal tachycardia that would trigger false positive detection. During the trial, the black-out time was programmed to 30 seconds. The heart rate changes for all stimulations and all patients were averaged.
Outcome measures
| Measure |
Reported by Investigators
n=30 Participants
All seizures that occurred during EMU stay and that were identified by investigators.
|
Reported by Triple Review
All seizures that occurred during EMU stay and that were identified by triple review post EMU.
|
Total
Seizures from an ITT subject that were either identified by the investigator during EMU evaluation or during the triple review process of EEG data.
|
Generalized Tonic Clonic Sz
NHS3 Scores at Follow-Up Visits
|
SSQ Scores at 24 Months
Change From Baseline at Each Category
|
|---|---|---|---|---|---|
|
Post-stimulation Heart Rate Changes
During Stimulation
|
0.74 percentage change
Standard Deviation 3.40
|
—
|
—
|
—
|
—
|
|
Post-stimulation Heart Rate Changes
Post Stimulation
|
0.09 percentage change
Standard Deviation 2.34
|
—
|
—
|
—
|
—
|
|
Post-stimulation Heart Rate Changes
Post Black-Out time
|
-0.01 percentage change
Standard Deviation 2.92
|
—
|
—
|
—
|
—
|
Adverse Events
VNS Therapy - Safety Population
Serious adverse events
| Measure |
VNS Therapy - Safety Population
n=31 participants at risk
All adverse events were collected from baseline up to the 24-month follow-up visit for all subjects treated/implanted with the AspireSR® VNS Therapy® system. All SAEs are reported in the SAE data table, whereas only the most common AEs (\> 5%) are reported in the AE data table.
|
|---|---|
|
Cardiac disorders
Cardiac Arrest
|
3.2%
1/31 • Number of events 1 • From baseline up to 24 Months
|
|
Skin and subcutaneous tissue disorders
Hemorrhage Subcutaneous
|
3.2%
1/31 • Number of events 1 • From baseline up to 24 Months
|
|
Nervous system disorders
Convulsion
|
9.7%
3/31 • Number of events 3 • From baseline up to 24 Months
|
|
Nervous system disorders
Aphonia
|
3.2%
1/31 • Number of events 1 • From baseline up to 24 Months
|
|
Nervous system disorders
Status Epilepticus
|
3.2%
1/31 • Number of events 1 • From baseline up to 24 Months
|
|
Injury, poisoning and procedural complications
Femur Fracture
|
3.2%
1/31 • Number of events 1 • From baseline up to 24 Months
|
|
Injury, poisoning and procedural complications
Incision Site Pain
|
3.2%
1/31 • Number of events 1 • From baseline up to 24 Months
|
|
Injury, poisoning and procedural complications
Tibia Fracture
|
3.2%
1/31 • Number of events 1 • From baseline up to 24 Months
|
|
Gastrointestinal disorders
Diarrhea
|
3.2%
1/31 • Number of events 1 • From baseline up to 24 Months
|
|
Gastrointestinal disorders
Vomiting
|
3.2%
1/31 • Number of events 1 • From baseline up to 24 Months
|
|
General disorders
Asthenia
|
3.2%
1/31 • Number of events 1 • From baseline up to 24 Months
|
|
Infections and infestations
Tooth Abscess
|
3.2%
1/31 • Number of events 1 • From baseline up to 24 Months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer
|
3.2%
1/31 • Number of events 1 • From baseline up to 24 Months
|
|
Psychiatric disorders
Depression
|
3.2%
1/31 • Number of events 1 • From baseline up to 24 Months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
3.2%
1/31 • Number of events 1 • From baseline up to 24 Months
|
|
Psychiatric disorders
Psychotic Disorder
|
3.2%
1/31 • Number of events 1 • From baseline up to 24 Months
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
3.2%
1/31 • Number of events 1 • From baseline up to 24 Months
|
Other adverse events
| Measure |
VNS Therapy - Safety Population
n=31 participants at risk
All adverse events were collected from baseline up to the 24-month follow-up visit for all subjects treated/implanted with the AspireSR® VNS Therapy® system. All SAEs are reported in the SAE data table, whereas only the most common AEs (\> 5%) are reported in the AE data table.
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
32.3%
10/31 • Number of events 10 • From baseline up to 24 Months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea Exertional
|
9.7%
3/31 • Number of events 3 • From baseline up to 24 Months
|
|
Nervous system disorders
Headache
|
16.1%
5/31 • Number of events 5 • From baseline up to 24 Months
|
|
Nervous system disorders
Dizziness
|
9.7%
3/31 • Number of events 3 • From baseline up to 24 Months
|
|
Nervous system disorders
Paresthesia
|
6.5%
2/31 • Number of events 2 • From baseline up to 24 Months
|
|
General disorders
Medical Device Pain
|
6.5%
2/31 • Number of events 2 • From baseline up to 24 Months
|
|
Gastrointestinal disorders
Dysphagia
|
6.5%
2/31 • Number of events 2 • From baseline up to 24 Months
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
6.5%
2/31 • Number of events 2 • From baseline up to 24 Months
|
|
Vascular disorders
Hypertension
|
6.5%
2/31 • Number of events 2 • From baseline up to 24 Months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
6.5%
2/31 • Number of events 2 • From baseline up to 24 Months
|
|
Psychiatric disorders
Insomnia
|
6.5%
2/31 • Number of events 2 • From baseline up to 24 Months
|
|
Injury, poisoning and procedural complications
Fall
|
6.5%
2/31 • Number of events 2 • From baseline up to 24 Months
|
Additional Information
Wim Van Grunderbeek, Clinical Operations Manager Cyberonics Europe
Cyberonics Europe BVBA
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60