Seizure Detection and Automatic Magnet Mode Performance Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Cyberonics, Inc.
- Enrollment
- 31
- Locations
- 14
- Primary Endpoint
- Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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.
Outcomes
Primary Outcomes
Observed Sensitivity Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
Time Frame: 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
Potential False Positives Based on Heart Rate Increase Associated With Seizures by Randomized SDA Setting
Time Frame: 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.
Summary of Seizures Reported by Investigators and Triple Review
Time Frame: 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.
Modeled Sensitivity Based on Heart Rate Increase Associated With Seizures by SDA Setting Post-Processed Through Bench-top Device Simulant
Time Frame: 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.
Secondary Outcomes
- Characterization of Latency Period: Analysis of Observed Latency for True Positive Detections by Randomized SDA Setting(Epilepsy Monitoring Unit (EMU) Stay)
- Changes in Seizure Severity Based on Physician Reported Questionnaire (NHS3)(up to 24 Months Visit)
- Changes in Seizures Severity, Intensity & Post-Ictal Recovery Based on Patient Completed Seizure Severity Questionnaire (SSQ)(Up to 24 Month visit)
- Changes in Quality of Life on Patient Reported Questionnaire (QOLIE-31-P)(up to 24 Months Visit)
- Validation of Cardiac R-Wave Detection(At Implant, First Titration Visit, Day 1 EMU and 12 Months)
- Changes From Baseline in Seizure Frequency(Up to 24 Month visit)
- Human Factors and Usability of the AspireSR® VNS Therapy® System.(At implant/recovery up to EMU Discharge (2 to 4 weeks))
- 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)
- Proportion of Seizures Ending During Stimulation by Type(Epilepsy Monitoring Unit (EMU) Stay)
- 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)
- Overall Summary of Seizure Intensity by Subgroup(Historical Seizures and Seizures during Epilepsy Monitoing Unit Stay)
- Post-stimulation Heart Rate Changes(EMU stay)