CLINICAL OUTCOMES: EPILEPSY Deep Brain Stimulation

SANTE STUDY

SANTE (Stimulation of the Anterior Nucleus of the Thalamus in Epilepsy) was a multicenter, prospective, randomized, double-blind, parallel groups study intended to evaluate the safety and efficacy of bilateral stimulation of the anterior nucleus of the thalamus (ANT) as an adjunctive therapy for the treatment of medically refractory epilepsy, characterized by partial-onset (focal) seizures, with or without secondary generalization.

The study was conducted at 17 centers in the United States. The study enrolled 157 adult subjects, of which 110 were implanted.

The SANTE trial provides Level 1 Clinical Evidence for Medtronic Deep Brain Stimulation for Epilepsy. The outcomes of the study demonstrated the safety, effectiveness and long-term benefits of Deep Brain Stimulation therapy for medically refractory partial-onset (focal) seizures in adults.^1,2

EFFECTIVENESS RESULTS²

Reduced Seizure Frequency

• DBS for Epilepsy was shown to reduce median seizure frequency, and these results improved over time. Our therapy benefits were consistent and sustained over time.
• After seven years, patients experienced a median 75% reduction in seizure frequency from baseline.

Freedom From Seizures

• In the seven years after implant, twenty patients in the SANTE study (18%) reported a seizure-free interval of at least six months. Nine patients were seizure-free for over two continuous years during that time.
• 18% of patients were seizure-free for at least six months at any time between implant and year seven.

IMPROVED RESPONDER RATE

For patients receiving Medtronic Deep Brain Stimulation Therapy for Epilepsy in the SANTE study, the responder rate (percentage of subjects with ≥50% seizure reduction) was 43% (n=99) at one year and 74% (n=50) at year seven.

SUBGROUPS SEIZURE REDUCTION

Significant seizure reductions were observed for certain subgroups, including those with temporal seizure origin, and those with or without prior Vagus Nerve Stimulation at seven years compared to baseline.

FEWER SEIZURE-RELATED INJURIES

During the blinded phase, DBS was shown to significantly reduce patients’ most severe seizures, complex partial seizures, and incidence of epilepsy-related injury.

• After seven years, patients experienced a median 71% reduction in most severe seizures as compared to baseline.
• After seven years, patients experienced a median 78% reduction in complex partial seizures as compared to baseline.
• DBS improved seizure severity in years one through seven as measured by the Liverpool Seizure Severity Scale.
• During the blinded phase, the incidence of epilepsy-related injury was significantly higher in the control group (25%) compared to the active group (7%).

IMPROVED QUALITY OF LIFE

The SANTE study showed a significant increase in quality of life for patients with epilepsy. After seven years, 43% of patients experienced a clinically meaningful improvement in quality of life.

HIGH PATIENT SATISFACTION²

After 7 years, 84% of patients (54 out of 64) said they were satisfied or greatly satisfied with the results.

Safety Results²

Safety was assessed in the SANTE trial with 110 implanted subjects having a combined 713 device-years of device experience. The following summary reflects data on all active subjects, followed for a minimum of seven years after device implantation.

SURGICAL RISKS AND DEVICE COMPLICATIONS

Device-related serious adverse events (SAEs) were reported by 34.5% of subjects. Most occurred during the first few months after implant. The most frequent SAEs included:

• Lead(s) not within target requiring replacement (8.2%)
• Implant site infection (10.9%; 9 subjects required partial or full system explant)
• All other SAEs were reported in 1.8% or fewer subjects

No symptomatic hemorrhage events were associated with lead implant or replacements. Of eight intracranial hemorrhage events, one SAE in the long-term follow-up resulted in clinical symptoms and was attributed to a head injury after two seizure related falls. The event resolved without sequelae or surgical intervention.

The most frequent device-related adverse events were:

• Implant site pain in 31.8% total post implant (30.9% in 7 years)
• Paresthesia in 23.6% total post implant (23.6% in 7 years)

There were no unanticipated adverse device effects reported in the study.

SUSTAINED NEUROPSYCHOLOGICAL TEST SCORES

Neuropsychological test scores for mood and cognition were stable acutely during the blinded phase and long-term through seven years. No subject discontinued the study due to depression or memory impairment. However, self-reports of depression and memory impairment were higher in the active group during the blinded phase.

MEMORY

Memory impairment was reported in 30.9% of subjects at any time after implant (30.0% at 7 years). Of the 34 subjects who reported memory impairment, 38.2% had a history of memory impairment.

DEPRESSION

Depression was reported in 39.1% of subjects at any time after implant (37.3% in 7 years). Three events in three subjects were device related. Of the 43 subjects who reported depression, 65.1% had a prior history of depression.

SUICIDALITY

Twelve subjects (10.9%) reported 15 suicidality events after DBS implant. Nine of the 15 events were serious in seven subjects (6.4%). There was one completed suicide four years after implantation (not device related). Of seven subjects reporting suicidality SAEs, six had a medical history of depression or suicide attempt.

STATUS EPILEPTICUS

Status epilepticus was reported in seven subjects (6.4%) at the time of database cutoff:

• 4 events were nonconvulsive
• 6 subjects required hospitalization
• 3 events occurred in subjects who were not receiving stimulation

SUDDEN UNEXPLAINED DEATH IN EPILEPSY (SUDEP)

There were seven deaths that occurred at the time of the database cutoff:

• 1 probable SUDEP prior to device implantation
• 2 definite SUDEP
• 1 possible SUDEP

Including pilot studies, SUDEP rate (definite/probable) was 2.5 per 1,000 patient years including all follow-up.² Published SUDEP rate for epilepsy surgery candidates is 9.3 per 1,000 patient years.³ The three other deaths were attributed to completed suicide, cardiorespiratory arrest, and liver cancer.²