Epilepsy
Conditions
Keywords
Automatic Magnet Mode (AMM), Vagus Nerve Stimulation (VNS)
Brief summary
Obtain baseline clinical outcome data (Stage 1) upon which to base a subsequent study (Stage 2) of the Model 106 VNS implantable pulse generator
Detailed description
Prospective, observational, un-blinded, 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, and 6-month follow-up. After the 6-month follow-up, patients will continue follow-up for safety for approximately two years or until final regulatory approval of the product.
Interventions
DEVICEM106 VNS Therapy System
Sponsors
Cyberonics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a clinical diagnosis of medically refractory epilepsy with partial onset seizures suitable for implantation with the VNS Therapy System. * 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 must be at least 12 years old. * Patients must be in good general health and ambulatory. * Patient or guardian must be willing and able to complete informed consent/assent.
Exclusion criteria
* Patients have had a bilateral or left cervical vagotomy. * Patients currently using, 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 (MRI). * Patients have a history of implantation of the VNS Therapy. * Patients with an IQ known or estimated to be \< 70, history of depression requiring hospitalization, 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 1 year of study enrollment. * Patients with known clinically meaningful cardiovascular arrhythmias as well as patients with clinically meaningful cardiovascular arrhythmias determined by a 24-hour Holter recording obtained during the baseline period. * Patients dependent on alcohol or narcotic drugs as defined by DSM IV-TR within the past 2 years. * Patients with a history of psychogenic non-epileptic seizures. * Women who are pregnant. Women of childbearing age must take a pregnancy test and agree to use an approved method of contraception during the study. * Patients currently enrolled in another investigational study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estimate the Effect Size Associated With Objective Measures and Patient Self-reports of Clinical Outcomes Including Seizure Frequency, Seizure Severity, Seizure Duration, Seizure Intensity, and Post-ictal Duration. | Up to 18 Month Visit-End of Study | The purpose for determining the effect size was to power a stage 2 study. At the conclusion of stage 1 of the E-37 study, it was determined that another study would not be necessary as it would not provide incremental clinical benefit information above what has already been collected. Therefore, computation of effect size was not necessary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess Performance of the Tachycardia Detection Algorithm (Sensitivity) During an EMU Stay Based on ITT Population-Observed | 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 and non-seizure EEG segments were provided to independent reviewers to confirm seizure occurrence and define electrographic seizure onset times. Seizure onset times were then compared with observed M106 device detections at the least sensitive setting capable of detecting the seizure based on the corresponding change in heart rate. Threshold for AutoStim setting (1;70%, 2;60%, 3;50%, 4;40%, 5;30% and 6;20%). No subjects were assigned to settings 3 and 6 that had seizures with a corresponding heart rate increase of \>= 50% and \>= 20%, respectively. Number of participants is total number of subjects who experienced seizures during the EMU stay. Bootstrap confidence intervals using 3000 bootstrap samples. |
| Assess Performance of the Tachycardia Detection Algorithm (Sensitivity) During an EMU Stay Based on ITT Population-Modeled | 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. |
| Assess Non-seizure Related Stimulation Rate Per Hour During EMU Stay and Stair Stepper Exercise Periods | Epilepsy Monitoring Unit (EMU) Stay | Each day in the EMU, subjects exercised for up to 3 minutes stepping up and down at a submaximal effort level on a step stool. Subject's resting heart rate was compared with the calculated 85% of the patient's age-predicted maximum heart rate. This calculated heart rate was then used as termination criteria for the step test. Non-Seizure Detection Rate (previously known as Potential False Positive Rate) is defined as the total number of non-seizure detections summed for the group divided by the total evaluable monitoring time during the EMU. The non-seizure detection rate per hour was calculated at the various tachycardia detection settings for all subjects during EMU and during exercise activities (stair stepper). |
| Assess Characterization of Seizures (Duration and Cessation) | 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. |
| Assesses Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Up to 18 Month Visit-End of Study | 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. |
| Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Up to 18 Month Visit-End of Study | 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 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 and 18 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. |
| Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Up to 18 Month Visit-End of Study | Adult subjects (18 years and older) completed the Quality of Life in Epilepsy-Patient-Weighted (QOLIE-31-P) survey questionnaire at screening and safety follow-up visits. The range for QOLIE-31-P (Sub-domains) scale is 0-100. The higher the score the better quality of life. Mean QOLIE-31-P scores at 3, 6, 12 and 18 months were compared to baseline. MIC Thresholds as defined in Simon Borghs, Christine de la Loge, Joyce A. Cramer, defining minimally important change in QOLIE-31-P scores. |
| Assess Changes From Baseline in Seizure Frequency | Up to 18 Month Visit-End of Study | Seizure frequency was calculated at 3, 6,12 and 18 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 proportion of patients that achieved ≥50% seizure reduction per month from baseline by visit. |
| Summary of Seizures Reported by Investigators and Triple Review | Epilepsy Monitoring Unit (EMU) Stay | Seizure events were recorded during the EMU stay (only Automatic Stimulation Mode aka AutoStim ON) using vEEG and ECG to evaluate tachycardia detection algorithm performance. The threshold for the AutoStim feature (20-70%) was programmed for each subject, based upon the historical ictal elevation in heart rate for that subject, requiring the corresponding heart rate elevation above that of a moving baseline window. Number of seizures observed and reported by investigators during the EMU stay (several subjects had more than one type of seizure) were collected and also reviewed by three (3) independent and blinded reviewers for confirmation. Additionally, the reviewers identified new seizures while reviewing the study EMU stay vEEG. |
| Assess All Adverse Events to Outline the Tolerability Profile of the AspireSR® VNS Therapy® System | From initial titration visit (approximately 2 weeks after implantation) up to End of Study | All adverse events (AEs) occurring during the study were collected and incidence rates tabulated by System Organ Class and Preferred Term utilizing MedDRA version 16.1 dictionary. The incidence profile was used to assess differences in near term tolerability rates relative to standard VNS Therapy. |
| Evaluation of Human Factors and Usability of the AspireSR® VNS Therapy® System. | Up to 6 Month Visit | 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, the first day of EMU, the end of EMU, and the 6 month follow-up visit. Overall Usability was calculated as percentage of the users who found the overall usability of system to be easy-2 or extremely easy-1. |
| Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Up to 18 Month Visit-End of Study | At baseline and each follow-up visit, subjects completed a healthcare utilization questionnaire to report the number of unplanned inpatient hospitalizations, emergency room visits, outpatient hospitalizations, physician office visits. |
| Assess Changes in Healthcare Utilization: Number of Nights Spent at the Hospital | Up to 18 Month Visit-End of Study | At baseline and each follow-up visit, subjects completed a healthcare utilization questionnaire to report the number of nights spent at the hospital. |
| Assess Changes in Healthcare Utilization: Days Per Week Patients and Caregivers Could Not Work | Up to 18 Month Visit-End of Study | At baseline and each follow-up visit, subjects completed a healthcare utilization questionnaire to report the number of days per week of missed work because of health reasons. |
| Assess Changes in Healthcare Utilization: Number of Hours Per Week Caregivers Spent Caring for Patients. | Up to 18 Month Visit-End of Study | At baseline and each follow-up visit, subjects completed a healthcare utilization questionnaire to report the number of hours per week caregivers spent caring for patients. |
| Assess Changes in Healthcare Utilization: Number of Phone Calls to Physician | Up to 18 Month Visit-End of Study | At baseline and each follow-up visit, subjects completed a healthcare utilization questionnaire to report the number of phone calls to physicians. |
| Assess Percent Changes in Antiepileptic Drug (AED) Load From Baseline | Up to 18 Month Visit-End of Study | AED load were collected and measured from baseline.The AED load is calculated as the sum of all ratios of the total daily dose of each medication taken on the day of the visit over the defined daily dose of the medication for the main indication according to the WHO database. Positive median value indicates increased drug load. |
Countries
United States
Participant flow
Recruitment details
Eligible subjects were at least 12 years old, good general health suitable for VNS implant with refractory (drug-resistant) partial onset seizures and a history of ictal tachycardia, defined as heart rate above 100 beats per minute (bpm) during a seizure and at least a 55% increase or 35 bpm increase from baseline.
Pre-assignment details
A total of (22) subjects were screened; (2) did not meet study criteria, (20) were treated/implanted with the AspireSR® VNS Therapy® System.
Participants by arm
| Arm | Count |
|---|---|
| VNS Therapy (ITT Population) Subjects who were implanted with the AspireSR® VNS Therapy® System. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Baseline Visit | Subject did not meet entry criteria | 2 |
Baseline characteristics
| Characteristic | VNS Therapy (ITT Population) |
|---|---|
| Age, Continuous | 35.6 Years STANDARD_DEVIATION 14.1 |
| Age, Customized 18-29 years | 9 years |
| Age, Customized 30-39 years | 5 years |
| Age, Customized 40-49 years | 2 years |
| Age, Customized 50-59 years | 2 years |
| Age, Customized 60 years or older | 2 years |
| Age, Customized | 31 years |
| Cognitive Status Minimal Impairment | 6 participants |
| Cognitive Status Normal | 14 participants |
| Etiology Cryptogenic | 2 participants |
| Etiology Idiopathic Partial | 8 participants |
| Etiology Symptomatic Partial | 10 participants |
| Family history of seizures No | 12 participants |
| Family history of seizures Yes | 8 participants |
| Previous brain or Epilepsy surgery No | 12 participants |
| Previous brain or Epilepsy surgery Yes | 8 participants |
| Race/Ethnicity, Customized Black or African American | 2 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 participants |
| Race/Ethnicity, Customized White | 15 participants |
| Seizures with auras in past 2 months No | 7 participants |
| Seizures with auras in past 2 months Yes | 13 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 8 Participants |
| Time from diagnosis to VNS therapy | 21.2 years STANDARD_DEVIATION 15.3 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 20 |
| serious Total, serious adverse events | 3 / 20 |
Outcome results
Primary
Estimate the Effect Size Associated With Objective Measures and Patient Self-reports of Clinical Outcomes Including Seizure Frequency, Seizure Severity, Seizure Duration, Seizure Intensity, and Post-ictal Duration.
The purpose for determining the effect size was to power a stage 2 study. At the conclusion of stage 1 of the E-37 study, it was determined that another study would not be necessary as it would not provide incremental clinical benefit information above what has already been collected. Therefore, computation of effect size was not necessary.
Time frame: Up to 18 Month Visit-End of Study
Secondary
Assess All Adverse Events to Outline the Tolerability Profile of the AspireSR® VNS Therapy® System
All adverse events (AEs) occurring during the study were collected and incidence rates tabulated by System Organ Class and Preferred Term utilizing MedDRA version 16.1 dictionary. The incidence profile was used to assess differences in near term tolerability rates relative to standard VNS Therapy.
Time frame: From initial titration visit (approximately 2 weeks after implantation) up to End of Study
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reported By Investigators | Assess All Adverse Events to Outline the Tolerability Profile of the AspireSR® VNS Therapy® System | Convulsion | 6 Number of Participants |
| Reported By Investigators | Assess All Adverse Events to Outline the Tolerability Profile of the AspireSR® VNS Therapy® System | Dysphonia | 6 Number of Participants |
| Reported By Investigators | Assess All Adverse Events to Outline the Tolerability Profile of the AspireSR® VNS Therapy® System | Oropharyngeal Pain | 3 Number of Participants |
| Reported By Investigators | Assess All Adverse Events to Outline the Tolerability Profile of the AspireSR® VNS Therapy® System | Stress | 3 Number of Participants |
| Reported By Investigators | Assess All Adverse Events to Outline the Tolerability Profile of the AspireSR® VNS Therapy® System | Urinary Tract Infection | 2 Number of Participants |
| Reported By Investigators | Assess All Adverse Events to Outline the Tolerability Profile of the AspireSR® VNS Therapy® System | Contusion | 2 Number of Participants |
| Reported By Investigators | Assess All Adverse Events to Outline the Tolerability Profile of the AspireSR® VNS Therapy® System | Dysphagia | 2 Number of Participants |
| Reported By Investigators | Assess All Adverse Events to Outline the Tolerability Profile of the AspireSR® VNS Therapy® System | Headache | 2 Number of Participants |
| Reported By Investigators | Assess All Adverse Events to Outline the Tolerability Profile of the AspireSR® VNS Therapy® System | Tooth Fracture | 2 Number of Participants |
| Reported By Investigators | Assess All Adverse Events to Outline the Tolerability Profile of the AspireSR® VNS Therapy® System | Umblical Hernia | 2 Number of Participants |
Secondary
Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P)
Adult subjects (18 years and older) completed the Quality of Life in Epilepsy-Patient-Weighted (QOLIE-31-P) survey questionnaire at screening and safety follow-up visits. The range for QOLIE-31-P (Sub-domains) scale is 0-100. The higher the score the better quality of life. Mean QOLIE-31-P scores at 3, 6, 12 and 18 months were compared to baseline. MIC Thresholds as defined in Simon Borghs, Christine de la Loge, Joyce A. Cramer, defining minimally important change in QOLIE-31-P scores.
Time frame: Up to 18 Month Visit-End of Study
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reported By Investigators | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | QOLIE Overall Total Score; n=20,20,19,18 MIC=5.19 | 11.0 Units on a Scale | Standard Deviation 18.8 |
| Reported By Investigators | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Energy/Fatigue; n=20,20,20,19 MIC=5.25 | 2.7 Units on a Scale | Standard Deviation 25.6 |
| Reported By Investigators | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Emotional well being; n=20,20,20,18 MIC=4.76 | 7.7 Units on a Scale | Standard Deviation 25.4 |
| Reported By Investigators | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Social Functioning; n=19,20,20,18 MIC=3.95 | 11.0 Units on a Scale | Standard Deviation 25.9 |
| Reported By Investigators | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Cognitive Functioning; n=20,20,20,19 MIC=5.34 | 19.2 Units on a Scale | Standard Deviation 24.6 |
| Reported By Investigators | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Medication Effects; n=19,20,19,19 MIC=5.0 | 10.3 Units on a Scale | Standard Deviation 33.1 |
| Reported By Investigators | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Seizure Worry; n=20,20,20,19 MIC=7.42 | 16.4 Units on a Scale | Standard Deviation 32.2 |
| Reported By Investigators | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Overall Quality of Life; n=20,20,19,17 MIC=6.42 | 10.6 Units on a Scale | Standard Deviation 24.7 |
| Reported by Triple Review | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Medication Effects; n=19,20,19,19 MIC=5.0 | 8.1 Units on a Scale | Standard Deviation 30 |
| Reported by Triple Review | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Cognitive Functioning; n=20,20,20,19 MIC=5.34 | 19.0 Units on a Scale | Standard Deviation 24.4 |
| Reported by Triple Review | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Energy/Fatigue; n=20,20,20,19 MIC=5.25 | 4.0 Units on a Scale | Standard Deviation 22.7 |
| Reported by Triple Review | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Overall Quality of Life; n=20,20,19,17 MIC=6.42 | 14.6 Units on a Scale | Standard Deviation 27.8 |
| Reported by Triple Review | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Seizure Worry; n=20,20,20,19 MIC=7.42 | 16.9 Units on a Scale | Standard Deviation 28.6 |
| Reported by Triple Review | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Social Functioning; n=19,20,20,18 MIC=3.95 | 11.0 Units on a Scale | Standard Deviation 18.2 |
| Reported by Triple Review | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Emotional well being; n=20,20,20,18 MIC=4.76 | 8.7 Units on a Scale | Standard Deviation 27.7 |
| Reported by Triple Review | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | QOLIE Overall Total Score; n=20,20,19,18 MIC=5.19 | 11.8 Units on a Scale | Standard Deviation 19.1 |
| Total | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Seizure Worry; n=20,20,20,19 MIC=7.42 | 20.9 Units on a Scale | Standard Deviation 27.6 |
| Total | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Emotional well being; n=20,20,20,18 MIC=4.76 | 10.1 Units on a Scale | Standard Deviation 33.5 |
| Total | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Social Functioning; n=19,20,20,18 MIC=3.95 | 9.6 Units on a Scale | Standard Deviation 25.6 |
| Total | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Cognitive Functioning; n=20,20,20,19 MIC=5.34 | 16.6 Units on a Scale | Standard Deviation 30.4 |
| Total | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Medication Effects; n=19,20,19,19 MIC=5.0 | 10.4 Units on a Scale | Standard Deviation 37.5 |
| Total | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Overall Quality of Life; n=20,20,19,17 MIC=6.42 | 13.1 Units on a Scale | Standard Deviation 30.6 |
| Total | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | QOLIE Overall Total Score; n=20,20,19,18 MIC=5.19 | 13.3 Units on a Scale | Standard Deviation 23.6 |
| Total | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Energy/Fatigue; n=20,20,20,19 MIC=5.25 | 8.8 Units on a Scale | Standard Deviation 26.1 |
| Simple Partial Seizures | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Emotional well being; n=20,20,20,18 MIC=4.76 | 3.0 Units on a Scale | Standard Deviation 36.5 |
| Simple Partial Seizures | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Social Functioning; n=19,20,20,18 MIC=3.95 | 12.5 Units on a Scale | Standard Deviation 30.1 |
| Simple Partial Seizures | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Energy/Fatigue; n=20,20,20,19 MIC=5.25 | 6.1 Units on a Scale | Standard Deviation 32.4 |
| Simple Partial Seizures | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | QOLIE Overall Total Score; n=20,20,19,18 MIC=5.19 | 14.4 Units on a Scale | Standard Deviation 24.1 |
| Simple Partial Seizures | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Cognitive Functioning; n=20,20,20,19 MIC=5.34 | 16.3 Units on a Scale | Standard Deviation 32.7 |
| Simple Partial Seizures | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Overall Quality of Life; n=20,20,19,17 MIC=6.42 | 19.1 Units on a Scale | Standard Deviation 29.5 |
| Simple Partial Seizures | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Seizure Worry; n=20,20,20,19 MIC=7.42 | 23.3 Units on a Scale | Standard Deviation 29.2 |
| Simple Partial Seizures | Assess Changes From Baseline in Quality of Life Based on Patient Completed Questionnaire (QOLIE-31-P) | Medication Effects; n=19,20,19,19 MIC=5.0 | 16.7 Units on a Scale | Standard Deviation 33.2 |
Comparison: QOLIE Overall Totalp-value: 0.0192Signed Rank Test
Comparison: Energy/Fatiguep-value: 0.8069Signed Rank Test
Comparison: Emotional well beingp-value: 0.2416Signed Rank Test
Comparison: Social Functioningp-value: 0.1111Signed Rank Test
Comparison: Cognitive Functioningp-value: 0.0014Signed Rank Test
Comparison: Medication Effectsp-value: 0.3247Signed Rank Test
Comparison: Seizure Worryp-value: 0.0826Signed Rank Test
Comparison: Overall Quality of Lifep-value: 0.104Signed Rank Test
Comparison: QOLIE Overall Totalp-value: 0.0094Signed Rank Test
Comparison: Energy/Fatiguep-value: 0.5874Signed Rank Test
Comparison: Emotional well beingp-value: 0.1508Signed Rank Test
Comparison: Social Functioningp-value: 0.0136Signed Rank Test
Comparison: Cognitive Functioningp-value: 0.0015Signed Rank Test
Comparison: Medication Effectsp-value: 0.3522Signed Rank Test
Comparison: Seizure Worryp-value: 0.024Signed Rank Test
Comparison: Overall Quality of Lifep-value: 0.0353Signed Rank Test
Comparison: QOLIE Overall Total Scorep-value: 0.0361Signed Rank Test
Comparison: Energy/Fatiguep-value: 0.1921Signed Rank Test
Comparison: Emotional well beingp-value: 0.1639Signed Rank Test
Comparison: Social Functioningp-value: 0.1738Signed Rank Test
Comparison: Cognitive Functioningp-value: 0.0401Signed Rank Test
Comparison: Medication Effectsp-value: 0.2753Signed Rank Test
Comparison: Seizure Worryp-value: 0.0056Signed Rank Test
Comparison: Overall Quality of Lifep-value: 0.1173Signed Rank Test
Comparison: QOLIE Overall Totalp-value: 0.0268Signed Rank Test
Comparison: Energy/Fatigue Finalp-value: 0.4406Signed Rank Test
Comparison: Emotional Well Being Finalp-value: 0.7926Signed Rank Test
Comparison: Social Functioning Finalp-value: 0.0987Signed Rank Test
Comparison: Cognitive Functioning Finalp-value: 0.0361Signed Rank Test
Comparison: Medication Effects Finalp-value: 0.0615Signed Rank Test
Comparison: Seizure Worryp-value: 0.0024Signed Rank Test
Comparison: Overall Quality of Lifep-value: 0.0155Signed Rank Test
Secondary
Assess Changes From Baseline in Seizure Frequency
Seizure frequency was calculated at 3, 6,12 and 18 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 proportion of patients that achieved ≥50% seizure reduction per month from baseline by visit.
Time frame: Up to 18 Month Visit-End of Study
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reported By Investigators | Assess Changes From Baseline in Seizure Frequency | At 3-Month Visit; n=5,4 | 25 Percentage of Participants |
| Reported By Investigators | Assess Changes From Baseline in Seizure Frequency | At 6-Month Visit; n=7,7 | 35 Percentage of Participants |
| Reported By Investigators | Assess Changes From Baseline in Seizure Frequency | At 12-Month Visit; n=10,10 | 50 Percentage of Participants |
| Reported By Investigators | Assess Changes From Baseline in Seizure Frequency | At 18-Month Visit; n=11,11 | 55 Percentage of Participants |
| Reported by Triple Review | Assess Changes From Baseline in Seizure Frequency | At 18-Month Visit; n=11,11 | 55 Percentage of Participants |
| Reported by Triple Review | Assess Changes From Baseline in Seizure Frequency | At 3-Month Visit; n=5,4 | 20 Percentage of Participants |
| Reported by Triple Review | Assess Changes From Baseline in Seizure Frequency | At 12-Month Visit; n=10,10 | 50 Percentage of Participants |
| Reported by Triple Review | Assess Changes From Baseline in Seizure Frequency | At 6-Month Visit; n=7,7 | 35 Percentage of Participants |
Secondary
Assess Changes in Healthcare Utilization: Days Per Week Patients and Caregivers Could Not Work
At baseline and each follow-up visit, subjects completed a healthcare utilization questionnaire to report the number of days per week of missed work because of health reasons.
Time frame: Up to 18 Month Visit-End of Study
Population: ITT Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Reported By Investigators | Assess Changes in Healthcare Utilization: Days Per Week Patients and Caregivers Could Not Work | #of DD/WK Could not work or Play(Pt),n=18,18,19,20 | 0 Days Per Week |
| Reported By Investigators | Assess Changes in Healthcare Utilization: Days Per Week Patients and Caregivers Could Not Work | #of DD/WK Could not Work(Caregiver),n=18, 20,17,15 | 0 Days Per Week |
| Reported by Triple Review | Assess Changes in Healthcare Utilization: Days Per Week Patients and Caregivers Could Not Work | #of DD/WK Could not Work(Caregiver),n=18, 20,17,15 | 0 Days Per Week |
| Reported by Triple Review | Assess Changes in Healthcare Utilization: Days Per Week Patients and Caregivers Could Not Work | #of DD/WK Could not work or Play(Pt),n=18,18,19,20 | 0 Days Per Week |
| Total | Assess Changes in Healthcare Utilization: Days Per Week Patients and Caregivers Could Not Work | #of DD/WK Could not work or Play(Pt),n=18,18,19,20 | 0 Days Per Week |
| Total | Assess Changes in Healthcare Utilization: Days Per Week Patients and Caregivers Could Not Work | #of DD/WK Could not Work(Caregiver),n=18, 20,17,15 | 0 Days Per Week |
| Simple Partial Seizures | Assess Changes in Healthcare Utilization: Days Per Week Patients and Caregivers Could Not Work | #of DD/WK Could not work or Play(Pt),n=18,18,19,20 | 0 Days Per Week |
| Simple Partial Seizures | Assess Changes in Healthcare Utilization: Days Per Week Patients and Caregivers Could Not Work | #of DD/WK Could not Work(Caregiver),n=18, 20,17,15 | 0 Days Per Week |
Secondary
Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits.
At baseline and each follow-up visit, subjects completed a healthcare utilization questionnaire to report the number of unplanned inpatient hospitalizations, emergency room visits, outpatient hospitalizations, physician office visits.
Time frame: Up to 18 Month Visit-End of Study
Population: ITT Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Reported By Investigators | Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Inpatient Hospital visits, n=20, 20, 20, 20 | 0 Visits |
| Reported By Investigators | Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Emergency Room Visits, n=20, 20, 20, 20 | 0 Visits |
| Reported By Investigators | Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Outpatient Hospital Visits, n=20, 20, 20, 19 | 0 Visits |
| Reported By Investigators | Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Physician Office Visits, n=20, 20, 20, 20 | 0 Visits |
| Reported by Triple Review | Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Emergency Room Visits, n=20, 20, 20, 20 | 0 Visits |
| Reported by Triple Review | Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Outpatient Hospital Visits, n=20, 20, 20, 19 | 0 Visits |
| Reported by Triple Review | Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Physician Office Visits, n=20, 20, 20, 20 | 0 Visits |
| Reported by Triple Review | Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Inpatient Hospital visits, n=20, 20, 20, 20 | 0 Visits |
| Total | Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Outpatient Hospital Visits, n=20, 20, 20, 19 | 0 Visits |
| Total | Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Emergency Room Visits, n=20, 20, 20, 20 | 0 Visits |
| Total | Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Physician Office Visits, n=20, 20, 20, 20 | 0 Visits |
| Total | Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Inpatient Hospital visits, n=20, 20, 20, 20 | 0 Visits |
| Simple Partial Seizures | Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Physician Office Visits, n=20, 20, 20, 20 | 0 Visits |
| Simple Partial Seizures | Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Emergency Room Visits, n=20, 20, 20, 20 | 0 Visits |
| Simple Partial Seizures | Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Inpatient Hospital visits, n=20, 20, 20, 20 | 0 Visits |
| Simple Partial Seizures | Assess Changes in Healthcare Utilization: Inpatient Hospital Visits, Emergency Room Visits, Outpatient Hospitalizations and Physician Office Visits. | Outpatient Hospital Visits, n=20, 20, 20, 19 | 0 Visits |
Secondary
Assess Changes in Healthcare Utilization: Number of Hours Per Week Caregivers Spent Caring for Patients.
At baseline and each follow-up visit, subjects completed a healthcare utilization questionnaire to report the number of hours per week caregivers spent caring for patients.
Time frame: Up to 18 Month Visit-End of Study
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reported By Investigators | Assess Changes in Healthcare Utilization: Number of Hours Per Week Caregivers Spent Caring for Patients. | 2.0 Hours Per Week |
| Reported by Triple Review | Assess Changes in Healthcare Utilization: Number of Hours Per Week Caregivers Spent Caring for Patients. | 1.0 Hours Per Week |
| Total | Assess Changes in Healthcare Utilization: Number of Hours Per Week Caregivers Spent Caring for Patients. | 4.0 Hours Per Week |
| Simple Partial Seizures | Assess Changes in Healthcare Utilization: Number of Hours Per Week Caregivers Spent Caring for Patients. | 2.0 Hours Per Week |
Secondary
Assess Changes in Healthcare Utilization: Number of Nights Spent at the Hospital
At baseline and each follow-up visit, subjects completed a healthcare utilization questionnaire to report the number of nights spent at the hospital.
Time frame: Up to 18 Month Visit-End of Study
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reported By Investigators | Assess Changes in Healthcare Utilization: Number of Nights Spent at the Hospital | 0 Nights |
| Reported by Triple Review | Assess Changes in Healthcare Utilization: Number of Nights Spent at the Hospital | 0 Nights |
| Total | Assess Changes in Healthcare Utilization: Number of Nights Spent at the Hospital | 0 Nights |
| Simple Partial Seizures | Assess Changes in Healthcare Utilization: Number of Nights Spent at the Hospital | 0 Nights |
Secondary
Assess Changes in Healthcare Utilization: Number of Phone Calls to Physician
At baseline and each follow-up visit, subjects completed a healthcare utilization questionnaire to report the number of phone calls to physicians.
Time frame: Up to 18 Month Visit-End of Study
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reported By Investigators | Assess Changes in Healthcare Utilization: Number of Phone Calls to Physician | 0 Phone Calls |
| Reported by Triple Review | Assess Changes in Healthcare Utilization: Number of Phone Calls to Physician | 0 Phone Calls |
| Total | Assess Changes in Healthcare Utilization: Number of Phone Calls to Physician | 0 Phone Calls |
| Simple Partial Seizures | Assess Changes in Healthcare Utilization: Number of Phone Calls to Physician | 0 Phone Calls |
Secondary
Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed 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 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 and 18 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.
Time frame: Up to 18 Month Visit-End of Study
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reported By Investigators | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | SSQ Total Score n=19,20,20,17 MIC=0.48 | 1.349 Units on a Scale | Standard Deviation 1.488 |
| Reported By Investigators | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Postictal Physical Recovery; n=19,20,19,17MIC=0.48 | 1.123 Units on a Scale | Standard Deviation 2.803 |
| Reported By Investigators | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Postictal Emotional Recovery n=19,20,19,17MIC=0.34 | 1.351 Units on a Scale | Standard Deviation 2.43 |
| Reported By Investigators | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Activity During Seizure; n=15,17,16, 15 MIC=0.5 | 1.567 Units on a Scale | Standard Deviation 2.89 |
| Reported By Investigators | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Postictal Cognitive Recovery;n=19,20,19,17MIC=0.42 | 1.421 Units on a Scale | Standard Deviation 3.166 |
| Reported By Investigators | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Overall Recovery; n=19,20,19,17 MIC=0.39 | 1.298 Units on a Scale | Standard Deviation 2.215 |
| Reported By Investigators | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Overall Severity; n=19,20,20,17 MIC=0.48 | 1.246 Units on a Scale | Standard Deviation 2.137 |
| Reported by Triple Review | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Postictal Physical Recovery; n=19,20,19,17MIC=0.48 | 1.450 Units on a Scale | Standard Deviation 3.789 |
| Reported by Triple Review | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Overall Severity; n=19,20,20,17 MIC=0.48 | 1.383 Units on a Scale | Standard Deviation 2.238 |
| Reported by Triple Review | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Overall Recovery; n=19,20,19,17 MIC=0.39 | 1.489 Units on a Scale | Standard Deviation 2.57 |
| Reported by Triple Review | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Postictal Emotional Recovery n=19,20,19,17MIC=0.34 | 1.733 Units on a Scale | Standard Deviation 2.494 |
| Reported by Triple Review | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Postictal Cognitive Recovery;n=19,20,19,17MIC=0.42 | 1.283 Units on a Scale | Standard Deviation 3.436 |
| Reported by Triple Review | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Activity During Seizure; n=15,17,16, 15 MIC=0.5 | 1.294 Units on a Scale | Standard Deviation 2.84 |
| Reported by Triple Review | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | SSQ Total Score n=19,20,20,17 MIC=0.48 | 1.442 Units on a Scale | Standard Deviation 1.736 |
| Total | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Overall Severity; n=19,20,20,17 MIC=0.48 | 1.767 Units on a Scale | Standard Deviation 2.717 |
| Total | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | SSQ Total Score n=19,20,20,17 MIC=0.48 | 1.469 Units on a Scale | Standard Deviation 1.908 |
| Total | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Activity During Seizure; n=15,17,16, 15 MIC=0.5 | 1.469 Units on a Scale | Standard Deviation 2.895 |
| Total | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Overall Recovery; n=19,20,19,17 MIC=0.39 | 1.942 Units on a Scale | Standard Deviation 2.817 |
| Total | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Postictal Emotional Recovery n=19,20,19,17MIC=0.34 | 1.825 Units on a Scale | Standard Deviation 2.838 |
| Total | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Postictal Physical Recovery; n=19,20,19,17MIC=0.48 | 2.088 Units on a Scale | Standard Deviation 3.778 |
| Total | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Postictal Cognitive Recovery;n=19,20,19,17MIC=0.42 | 1.912 Units on a Scale | Standard Deviation 3.878 |
| Simple Partial Seizures | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Overall Recovery; n=19,20,19,17 MIC=0.39 | 1.922 Units on a Scale | Standard Deviation 1.862 |
| Simple Partial Seizures | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Postictal Cognitive Recovery;n=19,20,19,17MIC=0.42 | 1.745 Units on a Scale | Standard Deviation 2.917 |
| Simple Partial Seizures | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Postictal Physical Recovery; n=19,20,19,17MIC=0.48 | 2.098 Units on a Scale | Standard Deviation 2.71 |
| Simple Partial Seizures | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Activity During Seizure; n=15,17,16, 15 MIC=0.5 | 1.200 Units on a Scale | Standard Deviation 2.242 |
| Simple Partial Seizures | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | SSQ Total Score n=19,20,20,17 MIC=0.48 | 1.711 Units on a Scale | Standard Deviation 1.389 |
| Simple Partial Seizures | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Postictal Emotional Recovery n=19,20,19,17MIC=0.34 | 1.922 Units on a Scale | Standard Deviation 2.631 |
| Simple Partial Seizures | Assess Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Questionnaire (SSQ) | Overall Severity; n=19,20,20,17 MIC=0.48 | 1.765 Units on a Scale | Standard Deviation 1.711 |
Comparison: SSQ Total Scorep-value: 0.0008Signed Rank Test
Comparison: Activity During Seizure Scorep-value: 0.0544Signed Rank Test
Comparison: Overall Recovery Scorep-value: 0.0207Signed Rank Test
Comparison: Overall Severity Scorep-value: 0.0163Signed Rank Test
Comparison: Postictal Emotional Recovery Scorep-value: 0.0156Signed Rank Test
Comparison: Postictal Physical Recovery Scorep-value: 0.0742Signed Rank Test
Comparison: Postictal Cognitive Recovery Scorep-value: 0.0884Signed Rank Test
Comparison: SSQ Total Scorep-value: 0.0007Signed Rank Test
Comparison: Activity During Seizurep-value: 0.1173Signed Rank Test
Comparison: Overall Recoveryp-value: 0.0214Signed Rank Test
Comparison: Overall Severityp-value: 0.0114Signed Rank Test
Comparison: Postictal Emotional Recoveryp-value: 0.0078Signed Rank Test
Comparison: Postictal Physical Recoveryp-value: 0.0875Signed Rank Test
Comparison: Postictal Cognitive Recoveryp-value: 0.1526Signed Rank Test
Comparison: SSQ Total Scorep-value: 0.0031Signed Rank Test
Comparison: Activity During Seizurep-value: 0.0828Signed Rank Test
Comparison: Overall Recoveryp-value: 0.0092Signed Rank Test
Comparison: Overall Severityp-value: 0.0096Signed Rank Test
Comparison: Postictal Emotional Recoveryp-value: 0.0234Signed Rank Test
Comparison: Postictal Physical Recoveryp-value: 0.0284Signed Rank Test
Comparison: Postictal Cognitive Recoveryp-value: 0.0679Signed Rank Test
Comparison: SSQ Total Scorep-value: 0.0003Signed Rank Test
Comparison: Activity During Seizures Scorep-value: 0.0728Signed Rank Test
Comparison: Overall Recovery Scorep-value: 0.0005Signed Rank Test
Comparison: Overall Severity Scorep-value: 0.0005Signed Rank Test
Comparison: Postictal Emotional Recovery Scorep-value: 0.0078Signed Rank Test
Comparison: Postictal Physical Recovery Scorep-value: 0.0078Signed Rank Test
Comparison: Postictal Cognitive Recovery Scorep-value: 0.0273Signed Rank Test
Secondary
Assess Characterization of Seizures (Duration and Cessation)
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reported By Investigators | Assess Characterization of Seizures (Duration and Cessation) | 61.3 Percent of Seizures Ended During Stim |
| Reported by Triple Review | Assess Characterization of Seizures (Duration and Cessation) | 41.7 Percent of Seizures Ended During Stim |
| Total | Assess Characterization of Seizures (Duration and Cessation) | 0 Percent of Seizures Ended During Stim |
| Simple Partial Seizures | Assess Characterization of Seizures (Duration and Cessation) | 83.3 Percent of Seizures Ended During Stim |
| Sub-Clinical Seizures | Assess Characterization of Seizures (Duration and Cessation) | 75.0 Percent of Seizures Ended During Stim |
| Unknown Seizures | Assess Characterization of Seizures (Duration and Cessation) | 50.0 Percent of Seizures Ended During Stim |
Secondary
Assesses 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 18 Month Visit-End of Study
Population: ITT Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Reported By Investigators | Assesses Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 3 Months; n=17,2,9 | -2.0 units on a scale |
| Reported By Investigators | Assesses Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 6 Months; n=17,4,11 | -0.5 units on a scale |
| Reported By Investigators | Assesses Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 12 Months; n=18,6,10 | -1.0 units on a scale |
| Reported By Investigators | Assesses Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 18 Months; n=15, 6, 9 | -3.0 units on a scale |
| Reported by Triple Review | Assesses Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 18 Months; n=15, 6, 9 | -2.5 units on a scale |
| Reported by Triple Review | Assesses Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 3 Months; n=17,2,9 | -3.5 units on a scale |
| Reported by Triple Review | Assesses Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 12 Months; n=18,6,10 | -3.0 units on a scale |
| Reported by Triple Review | Assesses Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 6 Months; n=17,4,11 | -1.0 units on a scale |
| Total | Assesses Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 18 Months; n=15, 6, 9 | 0.0 units on a scale |
| Total | Assesses Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 6 Months; n=17,4,11 | 0.0 units on a scale |
| Total | Assesses Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 12 Months; n=18,6,10 | 0.0 units on a scale |
| Total | Assesses Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3) | Baseline to 3 Months; n=17,2,9 | 0.0 units on a scale |
Comparison: Baseline to 3 monthsp-value: 0.008Signed Rank Test
Comparison: Baseline to 6 monthsp-value: 0.04Signed Rank Test
Comparison: Baseline to 12 monthsp-value: 0.033Signed Rank Test
Comparison: Baseline to 3 monthsp-value: 0.5Signed Rank Test
Comparison: Baseline to 6 monthsp-value: 0.75Signed Rank Test
Comparison: Baseline to 12 monthsp-value: 0.156Signed Rank Test
Comparison: Baseline to 3 monthsp-value: 0.938Signed Rank Test
Comparison: Baseline to 12 monthsp-value: 0.999Signed Rank Test
Comparison: Baseline to 6 monthsp-value: 0.25Signed Rank Test
Comparison: Baseline to 18 Monthsp-value: 0.057Signed Rank Test
Comparison: Baseline to 18 Monthsp-value: 0.031Signed Rank Test
Comparison: Baseline to 18 Monthsp-value: 0.625Signed Rank Test
Secondary
Assess Non-seizure Related Stimulation Rate Per Hour During EMU Stay and Stair Stepper Exercise Periods
Each day in the EMU, subjects exercised for up to 3 minutes stepping up and down at a submaximal effort level on a step stool. Subject's resting heart rate was compared with the calculated 85% of the patient's age-predicted maximum heart rate. This calculated heart rate was then used as termination criteria for the step test. Non-Seizure Detection Rate (previously known as Potential False Positive Rate) is defined as the total number of non-seizure detections summed for the group divided by the total evaluable monitoring time during the EMU. The non-seizure detection rate per hour was calculated at the various tachycardia detection settings for all subjects during EMU and during exercise activities (stair stepper).
Time frame: Epilepsy Monitoring Unit (EMU) Stay
Population: ITT Population. 5 participants analyzed for \>=70%, 4 for \>=60% setting, 8 for \>=50% setting, 2 for \>=40% setting, 1 for the \>=30% setting.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reported By Investigators | Assess Non-seizure Related Stimulation Rate Per Hour During EMU Stay and Stair Stepper Exercise Periods | >=60%, n=4 | 0.8 detections per hour |
| Reported By Investigators | Assess Non-seizure Related Stimulation Rate Per Hour During EMU Stay and Stair Stepper Exercise Periods | >=40%, n=2 | 0.6 detections per hour |
| Reported By Investigators | Assess Non-seizure Related Stimulation Rate Per Hour During EMU Stay and Stair Stepper Exercise Periods | >=50%, n=8 | 1.2 detections per hour |
| Reported By Investigators | Assess Non-seizure Related Stimulation Rate Per Hour During EMU Stay and Stair Stepper Exercise Periods | >= 30%, n=1 | 4.6 detections per hour |
| Reported By Investigators | Assess Non-seizure Related Stimulation Rate Per Hour During EMU Stay and Stair Stepper Exercise Periods | >=70%, n=5 | 0.4 detections per hour |
| Reported by Triple Review | Assess Non-seizure Related Stimulation Rate Per Hour During EMU Stay and Stair Stepper Exercise Periods | >= 30%, n=1 | 5.0 detections per hour |
| Reported by Triple Review | Assess Non-seizure Related Stimulation Rate Per Hour During EMU Stay and Stair Stepper Exercise Periods | >=70%, n=5 | 1.6 detections per hour |
| Reported by Triple Review | Assess Non-seizure Related Stimulation Rate Per Hour During EMU Stay and Stair Stepper Exercise Periods | >=60%, n=4 | 4.0 detections per hour |
| Reported by Triple Review | Assess Non-seizure Related Stimulation Rate Per Hour During EMU Stay and Stair Stepper Exercise Periods | >=50%, n=8 | 6.2 detections per hour |
| Reported by Triple Review | Assess Non-seizure Related Stimulation Rate Per Hour During EMU Stay and Stair Stepper Exercise Periods | >=40%, n=2 | 6.6 detections per hour |
Secondary
Assess Percent Changes in Antiepileptic Drug (AED) Load From Baseline
AED load were collected and measured from baseline.The AED load is calculated as the sum of all ratios of the total daily dose of each medication taken on the day of the visit over the defined daily dose of the medication for the main indication according to the WHO database. Positive median value indicates increased drug load.
Time frame: Up to 18 Month Visit-End of Study
Population: ITT Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Reported By Investigators | Assess Percent Changes in Antiepileptic Drug (AED) Load From Baseline | At 3 months | 0 Percent Change |
| Reported By Investigators | Assess Percent Changes in Antiepileptic Drug (AED) Load From Baseline | At 6 months | 0 Percent Change |
| Reported By Investigators | Assess Percent Changes in Antiepileptic Drug (AED) Load From Baseline | At 12 months | 3.35 Percent Change |
| Reported By Investigators | Assess Percent Changes in Antiepileptic Drug (AED) Load From Baseline | At 18 Months | 0 Percent Change |
Comparison: 3 monthsp-value: 0.0625Signed Rank Test
Comparison: 6 monthsp-value: 0.1094Signed Rank Test
Comparison: 12 monthsp-value: 0.0342Signed Rank Test
Comparison: 18 Monthsp-value: 0.5417Signed Rank Test
Secondary
Assess Performance of the Tachycardia Detection Algorithm (Sensitivity) During an EMU Stay Based on ITT Population-Modeled
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: ITT Population (Investigator Reported Seizures + Triple Review). N= represents total number of seizures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reported By Investigators | Assess Performance of the Tachycardia Detection Algorithm (Sensitivity) During an EMU Stay Based on ITT Population-Modeled | >= 70% heart rate increase at Setting 1 (n=8) | 87.5 Percent of True Positive Seizures |
| Reported By Investigators | Assess Performance of the Tachycardia Detection Algorithm (Sensitivity) During an EMU Stay Based on ITT Population-Modeled | >= 60% heart rate increase at Setting 2 (n=12) | 100 Percent of True Positive Seizures |
| Reported By Investigators | Assess Performance of the Tachycardia Detection Algorithm (Sensitivity) During an EMU Stay Based on ITT Population-Modeled | >= 50% heart rate increase at Setting 3 (n=20) | 95 Percent of True Positive Seizures |
| Reported By Investigators | Assess Performance of the Tachycardia Detection Algorithm (Sensitivity) During an EMU Stay Based on ITT Population-Modeled | >= 40% heart rate increase at Setting 4 (n=23) | 100 Percent of True Positive Seizures |
| Reported By Investigators | Assess Performance of the Tachycardia Detection Algorithm (Sensitivity) During an EMU Stay Based on ITT Population-Modeled | >= 30% heart rate increase at Setting 5 (n=31) | 100 Percent of True Positive Seizures |
| Reported By Investigators | Assess Performance of the Tachycardia Detection Algorithm (Sensitivity) During an EMU Stay Based on ITT Population-Modeled | >= 20% heart rate increase at Setting 6 (n=38) | 100 Percent of True Positive Seizures |
Secondary
Assess Performance of the Tachycardia Detection Algorithm (Sensitivity) During an EMU Stay Based on ITT Population-Observed
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 and non-seizure EEG segments were provided to independent reviewers to confirm seizure occurrence and define electrographic seizure onset times. Seizure onset times were then compared with observed M106 device detections at the least sensitive setting capable of detecting the seizure based on the corresponding change in heart rate. Threshold for AutoStim setting (1;70%, 2;60%, 3;50%, 4;40%, 5;30% and 6;20%). No subjects were assigned to settings 3 and 6 that had seizures with a corresponding heart rate increase of \>= 50% and \>= 20%, respectively. 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: ITT Population (Investigator Reported Seizures + Triple Review). N= represents total number of seizures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reported By Investigators | Assess Performance of the Tachycardia Detection Algorithm (Sensitivity) During an EMU Stay Based on ITT Population-Observed | >= 70% heart rate increase at Setting 1 (n=1) | 0 Percent of True Positive Seizures |
| Reported By Investigators | Assess Performance of the Tachycardia Detection Algorithm (Sensitivity) During an EMU Stay Based on ITT Population-Observed | >= 60% heart rate increase at Setting 2 (n=9) | 100 Percent of True Positive Seizures |
| Reported By Investigators | Assess Performance of the Tachycardia Detection Algorithm (Sensitivity) During an EMU Stay Based on ITT Population-Observed | >= 40% heart rate increase at Setting 4 (n=1) | 100 Percent of True Positive Seizures |
| Reported By Investigators | Assess Performance of the Tachycardia Detection Algorithm (Sensitivity) During an EMU Stay Based on ITT Population-Observed | >= 30% heart rate increase at Setting 5 (n=2) | 50 Percent of True Positive Seizures |
Secondary
Evaluation of 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, the first day of EMU, the end of EMU, and the 6 month follow-up visit. Overall Usability was calculated as percentage of the users who found the overall usability of system to be easy-2 or extremely easy-1.
Time frame: Up to 6 Month Visit
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reported By Investigators | Evaluation of Human Factors and Usability of the AspireSR® VNS Therapy® System. | 89 Percentage of Participants Rated 1 or 2 |
| Reported by Triple Review | Evaluation of Human Factors and Usability of the AspireSR® VNS Therapy® System. | 83 Percentage of Participants Rated 1 or 2 |
| Total | Evaluation of Human Factors and Usability of the AspireSR® VNS Therapy® System. | 95 Percentage of Participants Rated 1 or 2 |
| Simple Partial Seizures | Evaluation of Human Factors and Usability of the AspireSR® VNS Therapy® System. | 100 Percentage of Participants Rated 1 or 2 |
Secondary
Summary of Seizures Reported by Investigators and Triple Review
Seizure events were recorded during the EMU stay (only Automatic Stimulation Mode aka AutoStim ON) using vEEG and ECG to evaluate tachycardia detection algorithm performance. The threshold for the AutoStim feature (20-70%) was programmed for each subject, based upon the historical ictal elevation in heart rate for that subject, requiring the corresponding heart rate elevation above that of a moving baseline window. Number of seizures observed and reported by investigators during the EMU stay (several subjects had more than one type of seizure) were collected and also reviewed by three (3) independent and blinded reviewers for confirmation. Additionally, the reviewers identified new seizures while reviewing the study EMU stay vEEG.
Time frame: Epilepsy Monitoring Unit (EMU) Stay
Population: ITT Population: Consists of all patients in the safety population who have any EMU performance recorded data and experienced any seizures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reported By Investigators | Summary of Seizures Reported by Investigators and Triple Review | Total Partial Seizures | 76 Number of Seizures |
| Reported By Investigators | Summary of Seizures Reported by Investigators and Triple Review | All Seizure Types | 84 Number of Seizures |
| Reported By Investigators | Summary of Seizures Reported by Investigators and Triple Review | Complex Partial | 38 Number of Seizures |
| Reported By Investigators | Summary of Seizures Reported by Investigators and Triple Review | Unclassified | 0 Number of Seizures |
| Reported By Investigators | Summary of Seizures Reported by Investigators and Triple Review | Sub-Clinical | 8 Number of Seizures |
| Reported By Investigators | Summary of Seizures Reported by Investigators and Triple Review | Secondarily Generalized | 1 Number of Seizures |
| Reported By Investigators | Summary of Seizures Reported by Investigators and Triple Review | Simple Partial | 37 Number of Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | Secondarily Generalized | 0 Number of Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | Sub-Clinical | 1 Number of Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | Unclassified | 4 Number of Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | Simple Partial | 0 Number of Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | Complex Partial | 0 Number of Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | All Seizure Types | 5 Number of Seizures |
| Reported by Triple Review | Summary of Seizures Reported by Investigators and Triple Review | Total Partial Seizures | 0 Number of Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | Unclassified | 4 Number of Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | Total Partial Seizures | 76 Number of Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | Simple Partial | 37 Number of Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | Complex Partial | 38 Number of Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | Secondarily Generalized | 1 Number of Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | Sub-Clinical | 9 Number of Seizures |
| Total | Summary of Seizures Reported by Investigators and Triple Review | All Seizure Types | 89 Number of Seizures |