Epilepsy
Conditions
Keywords
Automatic Magnet Mode (AMM), Vagal Nerve Stimulation
Brief summary
The purpose of this study is to confirm cardiac-based seizure detection in Cyberonics Model 106 VNS Therapy System.
Detailed description
Prospective, observational, unblinded, multi-site study designed to collect data on patients implanted with a Model 106 VNS Therapy System from baseline through an EMU stay of up to 5 days. After the EMU stay, patients will continue follow-up for safety for approximately two years or until final regulatory approval of the product.
Interventions
DEVICEModel 106 VNS Therapy System
The VNS Therapy System is an adjunctive therapy for the treatment of epilepsy. VNS Therapy is available as a scheduled stimulation, this is cyclic stimulation between programmable On- and Off- times (e.g., a 30-second burst every 5 minutes). VNS Therapy is also available as on-demand stimulation, that is, when a magnet is introduced briefly over the implanted device (Magnet Mode). The AspireSR VNS Therapy System includes a new feature, Automatic Magnet Mode or AutoStim. In addition to Normal Mode and Magnet Mode, AspireSR uses a Seizure Detection Algorithm to identify a potential seizure onset based on associated heart rate increases known as ictal tachycardia. The purpose is to deliver stimulation at or near the onset of a seizure.
Sponsors
PRA Health Sciences
Cyberonics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a clinical diagnosis of medically refractory epilepsy dominated by partial seizures suitable for implantation with the Model 106 VNS Therapy System. * Patients with a history of increased heart rate (tachycardia) associated with seizure onset based on clinical data obtained from medical history, admission/hospital charts, or prior neurophysiologic evaluations. * Patients willing to undergo an EMU evaluation for a period of at least three days with activation of the AMM feature during that time. * Patients having an average of ≥ 3 seizures per month based upon diary or patient reporting for the 3 months prior to the screening visit. * Patients must have peak-peak R-wave amplitude greater than or equal to 0.40 mV on ECG measured from the proposed electrode location in the neck to the proposed generator location in the chest via surface ECG electrodes in 7 different body positions. * Patients must be at least 18 years old. * Patients must be in good general health and ambulatory. * Patient must be willing and able to complete informed consent.
Exclusion criteria
* Patients have had a bilateral or left cervical vagotomy. * Patients currently use, or are expected to use, short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy. * A VNS Therapy System implant would (in the investigator's judgment) pose an unacceptable surgical or medical risk for the patient. * Patients expected to require full body magnetic resonance imaging. * Patients have a history of VNS Therapy. * Patients have a documented history of clinically meaningful bradycardia (heart rate less than 50 bpm) associated with seizures. * Patients with a significant psychiatric disorder, significant cognitive impairment, history of major depression, or suicidality as defined by DSM IV-TR that in the investigator's judgment would pose an unacceptable risk for the patient or prevent the patient's successful completion of the study. * Patients with a history of status epilepticus within 3 months of study enrollment. * Patients prescribed drugs specifically for a cardiac or autonomic disorder that in the investigator's opinion would affect heart rate response unless the patient has ictal tachycardia while taking said drugs. These include, but are not limited to, beta adrenergic antagonists (beta blockers). * Patients with known clinically meaningful cardiovascular arrhythmias as well as patients with clinically meaningful cardiovascular arrhythmias determined by a 24-hour Holter recording obtained at the screening visit. * Patients dependent on alcohol or narcotic drugs as defined by DSM IV-TR within the past 2 years. * Patients with a history of only psychogenic or pseudo seizures. * Women who are pregnant. Women of childbearing age must take a pregnancy test. * Patients currently enrolled in another investigational study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Seizures Reported by Investigators and Triple Review | Epilepsy Monitoring Unit Stay | 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. |
| Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting | Epilepsy Monitoring Unit (EMU) Stay | 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 |
| Modeled Sensitivity Based on Heart Rate Increase Associated With Seizures by SDA Setting Post-Processed Through Bench-top Device Simulant | Epilepsy Monitoring Unit (EMU) Stay | 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. |
| Potential False Positives Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting | Epilepsy Monitoring Unit (EMU) Stay | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | up to 24 Months Visit | 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. |
| Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Seizure Severity Questionnaire (SSQ) | Up to 24 Month visit | 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 |
| Proportion of Seizures Ending During Stimulation by Type | Epilepsy Monitoring Unit (EMU) Stay | 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. |
| Summary of Seizure Duration (Seconds) for All Seizure Types by Subgroup(ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated) | Historical Seizures and Seizures during Epilepsy Monitoring Unit Stay | 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. |
| Validation of Cardiac R-Wave Detection | At Implant, First Titration Visit, Day 1 EMU and 12 Months | 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. |
| Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | up to 24 Months Visit | 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. |
| Overall Summary of Seizure Intensity by Subgroup | Historical Seizures and Seizures during Epilepsy Monitoing Unit Stay | 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 |
| Post-stimulation Heart Rate Changes | EMU stay | 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. |
| Summary of Post Ictal Duration (Seconds) for All Seizure Types (ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated) | Historical Seizures and Seizures during Epilepsy Monitoring Unit Stay | 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 |
| Characterization of Latency Period: Analysis of Observed Latency for True Positive Detections by Randomized SDA Setting | Epilepsy Monitoring Unit (EMU) Stay | 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. |
| Human Factors and Usability of the AspireSR® VNS Therapy® System. | At implant/recovery up to EMU Discharge (2 to 4 weeks) | 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. |
| Changes From Baseline in Seizure Frequency | Up to 24 Month visit | 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. |
Countries
Belgium, Germany, Netherlands, Norway, United Kingdom
Participant flow
Recruitment details
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.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| VNS Therapy (Safety Population) The safety population consists of all patients who provided consent and were implanted with the AspireSR VNS Therapy System version 1 or version 2. | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | VNS Therapy (Safety Population) |
|---|---|
| Age at Epilepsy Onset | 14 years |
| Age, Continuous | 39.6 years STANDARD_DEVIATION 13.4 |
| Age, Customized 18-29 years | 10 participants |
| Age, Customized 30-39 years | 8 participants |
| Age, Customized 40-49 years | 5 participants |
| Age, Customized 50-59 years | 5 participants |
| Age, Customized 60 years or older | 3 participants |
| Age, Customized | 38 years |
| Cognitive Status Minimal Impairment | 8 participants |
| Cognitive Status Moderate Impairment | 3 participants |
| Cognitive Status Normal | 20 participants |
| Cognitive Status Severe Impairment | 0 participants |
| Etiology Cryptogenic | 12 participants |
| Etiology Idiopathic | 3 participants |
| Etiology Symptomatic | 16 participants |
| Family History of Seizures No | 24 participants |
| Family History of Seizures Yes | 7 participants |
| Previous Brain or Epilepsy Surgery No | 22 participants |
| Previous Brain or Epilepsy Surgery Yes | 9 participants |
| Race/Ethnicity, Customized Other | 0 participants |
| Race/Ethnicity, Customized White | 31 participants |
| Region of Enrollment Belgium | 10 participants |
| Region of Enrollment Germany | 10 participants |
| Region of Enrollment Netherlands | 3 participants |
| Region of Enrollment Norway | 1 participants |
| Region of Enrollment United Kingdom | 7 participants |
| Seizures with Auras in the Past 2 Months No | 15 participants |
| Seizures with Auras in the Past 2 Months Yes | 16 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 26 / 31 |
| serious Total, serious adverse events | 10 / 31 |
Outcome results
Primary
Modeled Sensitivity Based on Heart Rate Increase Associated With Seizures by SDA Setting Post-Processed Through Bench-top Device Simulant
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.
Time frame: Epilepsy Monitoring Unit (EMU) Stay
Population: 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).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
Primary
Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
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
Time frame: Epilepsy Monitoring Unit (EMU) Stay
Population: 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).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
Primary
Potential False Positives Based on Heart Rate Increase Associated With Seizures by Randomized SDA 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.
Time frame: Epilepsy Monitoring Unit (EMU) Stay
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
Primary
Summary of Seizures Reported by Investigators and Triple Review
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.
Time frame: Epilepsy Monitoring Unit Stay
Population: ITT Population: consists of all patients implanted with the AspireSR VNS Therapy System version 2 and who have any EMU record.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reported by Investigators | Summary of Seizures Reported by Investigators and Triple Review | Sub-Clinical | 1 Seizures |
| Reported by Investigators | Summary of Seizures Reported by Investigators and Triple Review | Unknown | 3 Seizures |
| Reported by Investigators | Summary of Seizures Reported by Investigators and Triple Review | All Seizure Types | 87 Seizures |
| Reported by Investigators | Summary of Seizures Reported by Investigators and Triple Review | Other | 1 Seizures |
| Reported by Investigators | Summary of Seizures Reported by Investigators and Triple Review | Unclassified Seizure | 0 Seizures |
| Reported by Investigators | Summary of Seizures Reported by Investigators and Triple Review | Simple Partial | 26 Seizures |
| Reported by Investigators | Summary of Seizures Reported by Investigators and Triple Review | Total Partial | 82 Seizures |
| Reported by Investigators | Summary of Seizures Reported by Investigators and Triple Review | Complex Partial | 31 Seizures |
| Reported by Investigators | Summary of Seizures Reported by Investigators and Triple Review | Complex Partial with Secondary Generalization | 17 Seizures |
| Reported by Investigators | Summary of Seizures Reported by Investigators and Triple Review | Primary Generalized | 0 Seizures |
| Reported by Investigators | Summary of Seizures Reported by Investigators and Triple Review | Partial | 8 Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | Simple Partial | 0 Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | Sub-Clinical | 0 Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | Partial | 51 Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | Complex Partial with Secondary Generalization | 0 Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | Unknown | 0 Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | All Seizure Types | 124 Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | Complex Partial | 0 Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | Other | 0 Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | Total Partial | 51 Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | Unclassified Seizure | 30 Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | Primary Generalized | 43 Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | Unclassified Seizure | 30 Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | All Seizure Types | 211 Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | Total Partial | 133 Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | Partial | 59 Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | Simple Partial | 26 Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | Complex Partial | 31 Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | Complex Partial with Secondary Generalization | 17 Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | Primary Generalized | 43 Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | Sub-Clinical | 1 Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | Unknown | 3 Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | Other | 1 Seizures |
Secondary
Changes From Baseline in Seizure Frequency
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.
Time frame: Up to 24 Month visit
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reported by Investigators | Changes From Baseline in Seizure Frequency | Follow-up 6 Month n=30,28 | 20.0 Percentage of participants |
| Reported by Investigators | Changes From Baseline in Seizure Frequency | Follow-up 18 Month n=26,24 | 34.6 Percentage of participants |
| Reported by Investigators | Changes From Baseline in Seizure Frequency | Follow-up 12 Month n=27,25 | 33.3 Percentage of participants |
| Reported by Investigators | Changes From Baseline in Seizure Frequency | Follow-up 24 Month n=27,25 | 33.3 Percentage of participants |
| Reported by Investigators | Changes From Baseline in Seizure Frequency | Follow-up 3 Month n=29,27 | 24.1 Percentage of participants |
| Reported by Triple Review | Changes From Baseline in Seizure Frequency | Follow-up 24 Month n=27,25 | 36.0 Percentage of participants |
| Reported by Triple Review | Changes From Baseline in Seizure Frequency | Follow-up 3 Month n=29,27 | 25.9 Percentage of participants |
| Reported by Triple Review | Changes From Baseline in Seizure Frequency | Follow-up 6 Month n=30,28 | 25 Percentage of participants |
| Reported by Triple Review | Changes From Baseline in Seizure Frequency | Follow-up 12 Month n=27,25 | 36.0 Percentage of participants |
| Reported by Triple Review | Changes From Baseline in Seizure Frequency | Follow-up 18 Month n=26,24 | 37.5 Percentage of participants |
Secondary
Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P)
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.
Time frame: up to 24 Months Visit
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Triple Review | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Seizure Worry (MIC=7.42) n=28,29,28,28,26 | 2.1 units on a scale | Standard Deviation 24.4 |
| Reported by Triple Review | 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 17.9 |
| Reported by Triple Review | 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 | 6.2 units on a scale | Standard Deviation 25.4 |
| Reported by Triple Review | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Emotional Well Being (MIC=4.76) n=28,29,28,28,26 | -1.9 units on a scale | Standard Deviation 21.4 |
| Reported by Triple Review | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Social Functioning (MIC=3.95) n=27,28,26,27,26 | 11.6 units on a scale | Standard Deviation 26.3 |
| Reported by Triple Review | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | QOLIE Overall Total (MIC=5.19) n=28,29,28,28,26 | 4.4 units on a scale | Standard Deviation 18.7 |
| Reported by Triple Review | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Cognitive functioning (MIC=5.34) n=28,29,28,27,26 | 12.4 units on a scale | Standard Deviation 37.7 |
| Reported by Triple Review | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Medication Effects (MIC=5.00) n=28,29,28,26,26 | 3.3 units on a scale | Standard Deviation 27.5 |
| Total | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Energy/Fatigue (MIC=5.25) n=28,29,28,28,25 | 4.3 units on a scale | Standard Deviation 23.9 |
| Total | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Social Functioning (MIC=3.95) n=27,28,26,27,26 | 20.1 units on a scale | Standard Deviation 30.9 |
| Total | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Cognitive functioning (MIC=5.34) n=28,29,28,27,26 | 8.4 units on a scale | Standard Deviation 30.3 |
| Total | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | QOLIE Overall Total (MIC=5.19) n=28,29,28,28,26 | 8.9 units on a scale | Standard Deviation 18.4 |
| Total | 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 | 14.9 units on a scale | Standard Deviation 24.7 |
| Total | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Seizure Worry (MIC=7.42) n=28,29,28,28,26 | 7.7 units on a scale | Standard Deviation 27.9 |
| Total | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Medication Effects (MIC=5.00) n=28,29,28,26,26 | 0.9 units on a scale | Standard Deviation 21.4 |
| Total | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Emotional Well Being (MIC=4.76) n=28,29,28,28,26 | 7.1 units on a scale | Standard Deviation 23.9 |
| Generalized Tonic Clonic Sz | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Energy/Fatigue (MIC=5.25) n=28,29,28,28,25 | 4.9 units on a scale | Standard Deviation 21 |
| Generalized Tonic Clonic Sz | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Medication Effects (MIC=5.00) n=28,29,28,26,26 | 5.7 units on a scale | Standard Deviation 31.1 |
| Generalized Tonic Clonic Sz | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Social Functioning (MIC=3.95) n=27,28,26,27,26 | 14.6 units on a scale | Standard Deviation 18.6 |
| Generalized Tonic Clonic Sz | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | QOLIE Overall Total (MIC=5.19) n=28,29,28,28,26 | 10.2 units on a scale | Standard Deviation 15.9 |
| Generalized Tonic Clonic Sz | 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 | 15.0 units on a scale | Standard Deviation 23.1 |
| Generalized Tonic Clonic Sz | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Seizure Worry (MIC=7.42) n=28,29,28,28,26 | 8.1 units on a scale | Standard Deviation 18.9 |
| Generalized Tonic Clonic Sz | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Emotional Well Being (MIC=4.76) n=28,29,28,28,26 | 9.2 units on a scale | Standard Deviation 24.7 |
| Generalized Tonic Clonic Sz | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Cognitive functioning (MIC=5.34) n=28,29,28,27,26 | 13.6 units on a scale | Standard Deviation 30.4 |
| SSQ Scores at 24 Months | 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 | 16.0 units on a scale | Standard Deviation 31.2 |
| SSQ Scores at 24 Months | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Energy/Fatigue (MIC=5.25) n=28,29,28,28,25 | 6.9 units on a scale | Standard Deviation 23.6 |
| SSQ Scores at 24 Months | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Emotional Well Being (MIC=4.76) n=28,29,28,28,26 | 8.2 units on a scale | Standard Deviation 25.5 |
| SSQ Scores at 24 Months | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Social Functioning (MIC=3.95) n=27,28,26,27,26 | 10.2 units on a scale | Standard Deviation 27.7 |
| SSQ Scores at 24 Months | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Cognitive functioning (MIC=5.34) n=28,29,28,27,26 | 9.6 units on a scale | Standard Deviation 39.2 |
| SSQ Scores at 24 Months | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Medication Effects (MIC=5.00) n=28,29,28,26,26 | 1.1 units on a scale | Standard Deviation 40.1 |
| SSQ Scores at 24 Months | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | Seizure Worry (MIC=7.42) n=28,29,28,28,26 | 7.5 units on a scale | Standard Deviation 31 |
| SSQ Scores at 24 Months | Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P) | QOLIE Overall Total (MIC=5.19) n=28,29,28,28,26 | 8.7 units on a scale | Standard Deviation 25.3 |
Comparison: QOLIE Overall Totalp-value: 0.2079Signed Rank Test
Comparison: Energy/Fatigue Final Scorep-value: 0.6562Signed Rank Test
Comparison: Emotional well being Final Scorep-value: 0.9376Signed Rank Test
Comparison: Social Functioning Final Scorep-value: 0.01Signed Rank Test
Comparison: Cognitive functioning Final Scorep-value: 0.8532Signed Rank Test
Comparison: Medication Effects Final Scorep-value: 0.4954Signed Rank Test
Comparison: Seizure Worry Final Scorep-value: 0.1877Signed Rank Test
Comparison: Overall Quality of Life Final Scorep-value: 0.4189Signed Rank Test
Comparison: QOLIE Overall Total Scorep-value: 0.2365Signed Rank Test
Comparison: Energy/Fatigue Final Scorep-value: 0.4138Signed Rank Test
Comparison: Emotional well being Final Scorep-value: 0.8701Signed Rank Test
Comparison: Social Functioning Final Scorep-value: 0.0527Signed Rank Test
Comparison: Cognitive functioning Final Scorep-value: 0.1353Signed Rank Test
Comparison: Medication Effects Final Scorep-value: 0.6927Signed Rank Test
Comparison: Seizure Worry Final Scorep-value: 0.4964Signed Rank Test
Comparison: Overall Quality of Life Final Scorep-value: 0.0238Signed Rank Test
Comparison: QOLIE Overall Total Scorep-value: 0.0139Signed Rank Test
Comparison: Energy/Fatigue Final Scorep-value: 0.2822Signed Rank Test
Comparison: Emotional well being Final Scorep-value: 0.1363Signed Rank Test
Comparison: Social Functioning Final Scorep-value: 0.0019Signed Rank Test
Comparison: Cognitive functioning Final Scorep-value: 0.1293Signed Rank Test
Comparison: Medication Effects Final Scorep-value: 0.5252Signed Rank Test
Comparison: Seizure Worry Final Scorep-value: 0.0642Signed Rank Test
Comparison: Overall Quality of Life Final Scorep-value: 0.0025Signed Rank Test
Comparison: QOLIE Overall Total Scorep-value: 0.0024Signed Rank Test
Comparison: Energy/Fatigue Final Scorep-value: 0.4464Signed Rank Test
Comparison: Emotional well being Final Scorep-value: 0.0511Signed Rank Test
Comparison: Social Functioning Final Scorep-value: 0.0002Signed Rank Test
Comparison: Cognitive Functioning Final Scorep-value: 0.0296Signed Rank Test
Comparison: Medication Effects Final Scorep-value: 0.3115Signed Rank Test
Comparison: Seizure Worry Final Scorep-value: 0.027Signed Rank Test
Comparison: Overall Quality of Life Final Scorep-value: 0.0008Signed Rank Test
Comparison: QOLIE Overall Total Scorep-value: 0.0683Signed Rank Test
Comparison: Energy/Fatigue Final Scorep-value: 0.2226Signed Rank Test
Comparison: Emotional well being Final Scorep-value: 0.0823Signed Rank Test
Comparison: Social Functioning Final Scorep-value: 0.1459Signed Rank Test
Comparison: Cognitive Functioning Final Scorep-value: 0.261Signed Rank Test
p-value: 0.9119Signed Rank Test
Comparison: Seizure Worry Final Scorep-value: 0.0826Signed Rank Test
Comparison: Overall Quality of Life Final Scorep-value: 0.0036Signed Rank Test
Secondary
Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3)
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.
Time frame: up to 24 Months Visit
Population: ITT Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Triple Review | Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 24 Months; n=8,20,2,2 | -2.00 Units on a scale |
| Reported by Triple Review | Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 12 Months; n=9,20,6,5 | -1.83 Units on a scale |
| Reported by Triple Review | Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to EMU Discharge; n=11,19,5,3 | -1.00 Units on a scale |
| Reported by Triple Review | Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 6 Months; n=9,20,5,3 | -1.33 Units on a scale |
| Reported by Triple Review | Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 3 Months; n=12,20,6,2 | -1.00 Units on a scale |
| Reported by Triple Review | Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 18 Months; n=7,20,7,3 | -1.50 Units on a scale |
| Total | 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 |
| Total | 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 |
| Total | 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 |
| Total | Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 24 Months; n=8,20,2,2 | -2.00 Units on a scale |
| Total | Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 18 Months; n=7,20,7,3 | -1.0 Units on a scale |
| Total | 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 |
| Generalized Tonic Clonic Sz | Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 18 Months; n=7,20,7,3 | -7.00 Units on a scale |
| Generalized Tonic Clonic Sz | Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 24 Months; n=8,20,2,2 | -8.00 Units on a scale |
| Generalized Tonic Clonic Sz | Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 3 Months; n=12,20,6,2 | -6.50 Units on a scale |
| Generalized Tonic Clonic Sz | Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 12 Months; n=9,20,6,5 | -8.00 Units on a scale |
| Generalized Tonic Clonic Sz | Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to EMU Discharge; n=11,19,5,3 | -4.00 Units on a scale |
| Generalized Tonic Clonic Sz | 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 |
Comparison: Baseline to EMU Dischargep-value: 0.375Signed Rank Test
Comparison: Baseline to 3 Monthsp-value: 0.156Signed Rank Test
Comparison: Baseline to 6 monthsp-value: >0.999Signed Rank Test
Comparison: Baseline to 12 Monthsp-value: 0.906Signed Rank Test
Comparison: Baseline to 18 Monthsp-value: 0.188Signed Rank Test
Comparison: Baseline to 24 Monthsp-value: 0.906Signed Rank Test
Comparison: Baseline to EMU Dischargep-value: <0.001Signed Rank Test
Comparison: Baseline to 3 Monthsp-value: 0.106Signed Rank Test
Comparison: Baseline to 6 Monthsp-value: 0.012Signed Rank Test
Comparison: Baseline to 12 Monthsp-value: 0.008s
Comparison: Baseline to 18 Monthsp-value: 0.009Signed Rank Test
Comparison: Baseline to 24 Monthsp-value: 0.029Signed Rank Test
Comparison: Baseline to EMU Dischargep-value: 0.5s
Comparison: Baseline to 3 Monthsp-value: >0.999Signed Rank Test
Comparison: Baseline to 6 Monthsp-value: 0.5Signed Rank Test
Comparison: Baseline to 12 Monthsp-value: 0.5Signed Rank Test
Comparison: Baseline to 18 Monthsp-value: 0.188Signed Rank Test
Comparison: Baseline to 24 Monthsp-value: 0.5Signed Rank Test
Comparison: Baseline to EMU Dischargep-value: 0.5Signed Rank Test
Comparison: Baseline to 3 Monthsp-value: >0.999Signed Rank Test
Comparison: Baseline to 6 Monthsp-value: >0.999Signed Rank Test
Comparison: Baseline to 12 Monthsp-value: 0.125Signed Rank Test
Comparison: Baseline to 18 Monthsp-value: 0.5Signed Rank Test
Comparison: Baseline to 24 Monthsp-value: 0.5Signed Rank Test
Secondary
Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Seizure Severity Questionnaire (SSQ)
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
Time frame: Up to 24 Month visit
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Triple Review | 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 | 0.663 Units on a scale | Standard Deviation 2.125 |
| Reported by Triple Review | 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 | 0.589 Units on a scale | Standard Deviation 2.097 |
| Reported by Triple Review | 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 | 0.805 Units on a scale | Standard Deviation 2.832 |
| Reported by Triple Review | 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 | 0.567 Units on a scale | Standard Deviation 2.208 |
| Reported by Triple Review | 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 | 0.578 Units on a scale | Standard Deviation 2.946 |
| Reported by Triple Review | 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 | 0.728 Units on a scale | Standard Deviation 1.567 |
| Reported by Triple Review | 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 | 1.643 Units on a scale | Standard Deviation 2.714 |
| Total | 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 | 0.425 Units on a scale | Standard Deviation 2.486 |
| Total | 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 | 0.481 Units on a scale | Standard Deviation 2.514 |
| Total | 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 | 0.179 Units on a scale | Standard Deviation 3.093 |
| Total | 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 | 0.805 Units on a scale | Standard Deviation 2.814 |
| Total | 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 | 0.393 Units on a scale | Standard Deviation 3.012 |
| Total | 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 | 0.907 Units on a scale | Standard Deviation 2.557 |
| Total | 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 | 0.354 Units on a scale | Standard Deviation 1.64 |
| Generalized Tonic Clonic Sz | 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 | 0.476 Units on a scale | Standard Deviation 3.018 |
| Generalized Tonic Clonic Sz | 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 | 0.280 Units on a scale | Standard Deviation 2.913 |
| Generalized Tonic Clonic Sz | 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 | 0.800 Units on a scale | Standard Deviation 2.441 |
| Generalized Tonic Clonic Sz | 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 | 0.274 Units on a scale | Standard Deviation 3.587 |
| Generalized Tonic Clonic Sz | 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 | 0.341 Units on a scale | Standard Deviation 1.461 |
| Generalized Tonic Clonic Sz | 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 | -0.062 Units on a scale | Standard Deviation 3.48 |
| Generalized Tonic Clonic Sz | 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 | 0.131 Units on a scale | Standard Deviation 2.855 |
| SSQ Scores at 24 Months | 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 | 0.359 Units on a scale | Standard Deviation 3.124 |
| SSQ Scores at 24 Months | 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 | 0.012 Units on a scale | Standard Deviation 3.043 |
| SSQ Scores at 24 Months | 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 | 0.099 Units on a scale | Standard Deviation 3.404 |
| SSQ Scores at 24 Months | 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 | 0.218 Units on a scale | Standard Deviation 2.783 |
| SSQ Scores at 24 Months | 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 | 1.818 Units on a scale | Standard Deviation 2.982 |
| SSQ Scores at 24 Months | 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 | 0.966 Units on a scale | Standard Deviation 1.975 |
| SSQ Scores at 24 Months | 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 | 0.160 Units on a scale | Standard Deviation 2.806 |
Comparison: SSQ Total Scorep-value: 0.1529Signed Rank Test
Comparison: Activity During Seizures Scorep-value: 0.0942Signed Rank Test
Comparison: Overall Recovery Scorep-value: 0.2831Signed Rank Test
Comparison: Overall Severity Scorep-value: 0.3639Signed Rank Test
Comparison: Postictal Emotional Recovery Scorep-value: 0.447Signed Rank Test
Comparison: Postictal Physical Recovery Scorep-value: 0.1311s
Comparison: Postictal Cognitive Recovery Scorep-value: 0.3898Signed Rank Test
Comparison: SSQ Total Scorep-value: 0.0511Signed Rank Test
Comparison: Activity During Seizures Scorep-value: 0.0019Signed Rank Test
Comparison: Overall Recovery Scorep-value: 0.1106Signed Rank Test
Comparison: Overall Severity Scorep-value: 0.1273Signed Rank Test
Comparison: Postictal Emotional Recovery Scorep-value: 0.1305Signed Rank Test
Comparison: Postictal Physical Recovery Scorep-value: 0.1123Signed Rank Test
Comparison: Postictal Cognitive Recovery Scorep-value: 0.2309Signed Rank Test
Comparison: SSQ Total Scorep-value: 0.3191Signed Rank Test
Comparison: Activity During Seizures Scorep-value: 0.0679Signed Rank Test
Comparison: Overall Recovery Scorep-value: 0.2082Signed Rank Test
Comparison: Overall Severity Scorep-value: 0.179Signed Rank Test
Comparison: Postictal Emotional Recovery Scorep-value: 0.6869Signed Rank Test
Comparison: Postictal Physical Recovery Scorep-value: 0.6094Signed Rank Test
Comparison: Postictal Cognitive Recovery Scorep-value: 0.153Signed Rank Test
Comparison: SSQ Total Scorep-value: 0.3339Signed Rank Test
Comparison: Activity During Seizures Scorep-value: 0.1473Signed Rank Test
Comparison: Overall Recovery Scorep-value: 0.5035Signed Rank Test
Comparison: Overall Severity Scorep-value: 0.6653Signed Rank Test
Comparison: Postictal Emotional Recovery Scorep-value: 0.8622Signed Rank Test
Comparison: Postictal Physical Recovery Scorep-value: 0.4456Signed Rank Test
Comparison: Postictal Cognitive Recovery Scorep-value: 0.6876Signed Rank Test
Comparison: SSQ Total Scorep-value: 0.0328Signed Rank Test
Comparison: Activity During Seizures Scorep-value: 0.0067Signed Rank Test
Comparison: Overall Recovery Scorep-value: 0.5928Signed Rank Test
Comparison: Overall Severity Scorep-value: 0.7179Signed Rank Test
Comparison: Postictal Emotional Recovery Scorep-value: 0.5014Signed Rank Test
Comparison: Postictal Physical Recovery Scorep-value: 0.964Signed Rank Test
Comparison: Postictal Cognitive Recovery Scorep-value: 0.8537Signed Rank Test
Secondary
Characterization of Latency Period: Analysis of Observed Latency for True Positive Detections by Randomized SDA Setting
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.
Time frame: Epilepsy Monitoring Unit (EMU) Stay
Population: ITT Population n=total number of seizures in each category
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Reported by Investigators | Characterization of Latency Period: Analysis of Observed Latency for True Positive Detections by Randomized SDA Setting | SDA 2 (n=1, 8) | 4 seconds |
| Reported by Investigators | Characterization of Latency Period: Analysis of Observed Latency for True Positive Detections by Randomized SDA Setting | SDA 4 (n=6,8) | 27.5 seconds |
| Reported by Investigators | Characterization of Latency Period: Analysis of Observed Latency for True Positive Detections by Randomized SDA Setting | SDA 6 (n=2,37) | -14.5 seconds |
| Reported by Triple Review | Characterization of Latency Period: Analysis of Observed Latency for True Positive Detections by Randomized SDA Setting | SDA 2 (n=1, 8) | 19.5 seconds |
| Reported by Triple Review | Characterization of Latency Period: Analysis of Observed Latency for True Positive Detections by Randomized SDA Setting | SDA 4 (n=6,8) | 27.5 seconds |
| Reported by Triple Review | Characterization of Latency Period: Analysis of Observed Latency for True Positive Detections by Randomized SDA Setting | SDA 6 (n=2,37) | 7 seconds |
Secondary
Human Factors and Usability of the AspireSR® VNS Therapy® System.
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.
Time frame: At implant/recovery up to EMU Discharge (2 to 4 weeks)
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reported by Investigators | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Training Material (n=21, 23) | 76.2 Percentage of participants rated 1 or 2 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Interrogation (Short) (n=22, 24) | 86.4 Percentage of participants rated 1 or 2 |
| Reported by Investigators | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Interrogation (Long) (n=21, 24) | 57.1 Percentage of participants rated 1 or 2 |
| Reported by Investigators | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Change Parameters (n=22, 24) | 90.9 Percentage of participants rated 1 or 2 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | Human Factors and Usability of the AspireSR® VNS Therapy® System. | System Diagnostic (n=21,24) | 85.7 Percentage of participants rated 1 or 2 |
| Reported by Investigators | Human Factors and Usability of the AspireSR® VNS Therapy® System. | View Database (n=17, 22) | 58.8 Percentage of participants rated 1 or 2 |
| Reported by Investigators | 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 |
| Reported by Investigators | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Export Data (n=7, 15) | 100 Percentage of participants rated 1 or 2 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Warning Messages (n=13, 24) | 84.6 Percentage of participants rated 1 or 2 |
| Reported by Investigators | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Overall Usability (n=20, 24) | 80.0 Percentage of participants rated 1 or 2 |
| Reported by Triple Review | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Overall Usability (n=20, 24) | 70.8 Percentage of participants rated 1 or 2 |
| Reported by Triple Review | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Training Material (n=21, 23) | 73.9 Percentage of participants rated 1 or 2 |
| Reported by Triple Review | Human Factors and Usability of the AspireSR® VNS Therapy® System. | System Diagnostic (n=21,24) | 87.5 Percentage of participants rated 1 or 2 |
| Reported by Triple Review | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Physician's Manual (n=18, 20) | 70.0 Percentage of participants rated 1 or 2 |
| Reported by Triple Review | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Generator Battery Status Indicators (n=20, 24) | 87.5 Percentage of participants rated 1 or 2 |
| Reported by Triple Review | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Laminated Instruction Card (n=20, 21) | 81.0 Percentage of participants rated 1 or 2 |
| Reported by Triple Review | Human Factors and Usability of the AspireSR® VNS Therapy® System. | View Database (n=17, 22) | 72.7 Percentage of participants rated 1 or 2 |
| Reported by Triple Review | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Interrogation (Short) (n=22, 24) | 91.7 Percentage of participants rated 1 or 2 |
| Reported by Triple Review | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Warning Messages (n=13, 24) | 87.5 Percentage of participants rated 1 or 2 |
| Reported by Triple Review | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Interrogation (Long) (n=21, 24) | 83.3 Percentage of participants rated 1 or 2 |
| Reported by Triple Review | Human Factors and Usability of the AspireSR® VNS Therapy® System. | View Seizure Detection Data (n=15, 22) | 63.6 Percentage of participants rated 1 or 2 |
| Reported by Triple Review | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Change Parameters (n=22, 24) | 95.8 Percentage of participants rated 1 or 2 |
| Reported by Triple Review | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Handheld Battery Status Indicator (n=19, 24) | 83.3 Percentage of participants rated 1 or 2 |
| Reported by Triple Review | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Heartbeat Sensitivity Configuration (n=20, 24) | 83.3 Percentage of participants rated 1 or 2 |
| Reported by Triple Review | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Export Data (n=7, 15) | 66.7 Percentage of participants rated 1 or 2 |
| Reported by Triple Review | Human Factors and Usability of the AspireSR® VNS Therapy® System. | Seizure Detection Configuration (n=21, 23) | 82.6 Percentage of participants rated 1 or 2 |
Secondary
Overall Summary of Seizure Intensity by Subgroup
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
Time frame: Historical Seizures and Seizures during Epilepsy Monitoing Unit Stay
Population: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reported by Investigators | Overall Summary of Seizure Intensity by Subgroup | Simple Partial Seizures n=6, 8, 4, 0 | 33.9 unitless | Standard Deviation 33.9 |
| Reported by Investigators | Overall Summary of Seizure Intensity by Subgroup | Complex Partial Seizures n=60, 9, 6, 7 | 205.4 unitless | Standard Deviation 519.2 |
| Reported by Investigators | Overall Summary of Seizure Intensity by Subgroup | CPS Secondary generalized n=10, 2, 0, 0 | 435.1 unitless | Standard Deviation 654.7 |
| Reported by Investigators | Overall Summary of Seizure Intensity by Subgroup | Debilitating Seizures n=70, 12, 7, 7 | 238.2 unitless | Standard Deviation 541.2 |
| Reported by Triple Review | Overall Summary of Seizure Intensity by Subgroup | Complex Partial Seizures n=60, 9, 6, 7 | 989.4 unitless | Standard Deviation 2307 |
| Reported by Triple Review | Overall Summary of Seizure Intensity by Subgroup | CPS Secondary generalized n=10, 2, 0, 0 | 611.4 unitless | Standard Deviation 832.2 |
| Reported by Triple Review | Overall Summary of Seizure Intensity by Subgroup | Debilitating Seizures n=70, 12, 7, 7 | 852.1 unitless | Standard Deviation 2002.8 |
| Reported by Triple Review | Overall Summary of Seizure Intensity by Subgroup | Simple Partial Seizures n=6, 8, 4, 0 | 225.3 unitless | Standard Deviation 427.1 |
| Total | Overall Summary of Seizure Intensity by Subgroup | CPS Secondary generalized n=10, 2, 0, 0 | NA unitless | — |
| Total | Overall Summary of Seizure Intensity by Subgroup | Complex Partial Seizures n=60, 9, 6, 7 | 59.5 unitless | Standard Deviation 65.2 |
| Total | Overall Summary of Seizure Intensity by Subgroup | Debilitating Seizures n=70, 12, 7, 7 | 65.0 unitless | Standard Deviation 61.3 |
| Total | Overall Summary of Seizure Intensity by Subgroup | Simple Partial Seizures n=6, 8, 4, 0 | 406.6 unitless | Standard Deviation 581 |
| Generalized Tonic Clonic Sz | Overall Summary of Seizure Intensity by Subgroup | Debilitating Seizures n=70, 12, 7, 7 | 51.6 unitless | Standard Deviation 74.7 |
| Generalized Tonic Clonic Sz | Overall Summary of Seizure Intensity by Subgroup | Complex Partial Seizures n=60, 9, 6, 7 | 51.6 unitless | Standard Deviation 74.7 |
| Generalized Tonic Clonic Sz | Overall Summary of Seizure Intensity by Subgroup | Simple Partial Seizures n=6, 8, 4, 0 | NA unitless | — |
| Generalized Tonic Clonic Sz | Overall Summary of Seizure Intensity by Subgroup | CPS Secondary generalized n=10, 2, 0, 0 | NA unitless | — |
Secondary
Post-stimulation Heart Rate Changes
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.
Time frame: EMU stay
Population: ITT population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reported by Investigators | Post-stimulation Heart Rate Changes | During Stimulation | 0.74 percentage change | Standard Deviation 3.4 |
| Reported by Investigators | Post-stimulation Heart Rate Changes | Post Stimulation | 0.09 percentage change | Standard Deviation 2.34 |
| Reported by Investigators | Post-stimulation Heart Rate Changes | Post Black-Out time | -0.01 percentage change | Standard Deviation 2.92 |
Secondary
Proportion of Seizures Ending During Stimulation by Type
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.
Time frame: Epilepsy Monitoring Unit (EMU) Stay
Population: ITT Population; All Treated Seizures n=total number of seizures
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reported by Investigators | Proportion of Seizures Ending During Stimulation by Type | Overall (n=33) | 57.6 Percentage of Seizures Ending |
| Reported by Investigators | Proportion of Seizures Ending During Stimulation by Type | Partial Seizures (not otherwise specified) (n=5) | 20 Percentage of Seizures Ending |
| Reported by Investigators | Proportion of Seizures Ending During Stimulation by Type | Simple Partial Seizures (n=4) | 100 Percentage of Seizures Ending |
| Reported by Investigators | Proportion of Seizures Ending During Stimulation by Type | Complex Partial Seizures (n=11) | 54.5 Percentage of Seizures Ending |
| Reported by Investigators | Proportion of Seizures Ending During Stimulation by Type | Secondary Generalized Seizures (n=2) | 0.0 Percentage of Seizures Ending |
| Reported by Investigators | Proportion of Seizures Ending During Stimulation by Type | Generalized Seizures (n=9) | 66.7 Percentage of Seizures Ending |
| Reported by Investigators | Proportion of Seizures Ending During Stimulation by Type | Debilitating Seizures (CPS, SGS, GEN) (n=22) | 54.5 Percentage of Seizures Ending |
| Reported by Investigators | Proportion of Seizures Ending During Stimulation by Type | Unknown Type (n=2) | 100 Percentage of Seizures Ending |
Secondary
Summary of Post Ictal Duration (Seconds) for All Seizure Types (ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated)
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
Time frame: Historical Seizures and Seizures during Epilepsy Monitoring Unit Stay
Population: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reported by Investigators | 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 | — |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Triple Review | 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 | NA Seconds | — |
| Reported by Triple Review | 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 | 102.8 Seconds | Standard Deviation 110.2 |
| Reported by Triple Review | 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 | 85.7 Seconds | Standard Deviation 81.7 |
| Reported by Triple Review | 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 | 9.4 Seconds | Standard Deviation 0 |
| Reported by Triple Review | 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 | 74.8 Seconds | Standard Deviation 79.9 |
| Total | 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 | 66.6 Seconds | Standard Deviation 99.9 |
| Total | 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 | — |
| Total | 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 | NA Seconds | — |
| Total | 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 | NA Seconds | — |
| Total | 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 | 66.6 Seconds | Standard Deviation 99.9 |
Secondary
Summary of Seizure Duration (Seconds) for All Seizure Types by Subgroup(ITT Population) (Only Seizures With Post Ictal Duration (Seconds) Annotated)
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.
Time frame: Historical Seizures and Seizures during Epilepsy Monitoring Unit Stay
Population: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reported by Investigators | 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 | — |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Investigators | 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 |
| Reported by Triple Review | 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 | 26.8 Seconds | Standard Deviation 16.2 |
| Reported by Triple Review | 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 | 40.5 Seconds | Standard Deviation 32.1 |
| Reported by Triple Review | 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 | NA Seconds | — |
| Reported by Triple Review | 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 | 20.3 Seconds | Standard Deviation 10.4 |
| Reported by Triple Review | 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 | 23.6 Seconds | Standard Deviation 13.4 |
| Total | 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 | 150.7 Seconds | Standard Deviation 153.6 |
| Total | 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 | — |
| Total | 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 | NA Seconds | — |
| Total | 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 | NA Seconds | — |
| Total | 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 | 150.7 Seconds | Standard Deviation 153.6 |
Secondary
Validation of Cardiac R-Wave Detection
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.
Time frame: At Implant, First Titration Visit, Day 1 EMU and 12 Months
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reported by Investigators | Validation of Cardiac R-Wave Detection | At Implant (n=26) | 95.52 percentage of beats accurately detected |
| Reported by Investigators | Validation of Cardiac R-Wave Detection | First Titration Visit (n=19) | 98.74 percentage of beats accurately detected |
| Reported by Investigators | Validation of Cardiac R-Wave Detection | EMU Day 1 (n=29) | 99.71 percentage of beats accurately detected |
| Reported by Investigators | Validation of Cardiac R-Wave Detection | 12 Month Follow-up (n=14) | 99.43 percentage of beats accurately detected |