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 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 study's outcomes demonstrated the safety, effectiveness and long-term benefits of Deep Brain Stimulation therapy for medically refractory partial-onset (focal) seizures in adults.6,7
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.
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 straight years during that time.
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.
Increase in rate of ANT DBS-treated patients who met the responder criteria over 7 years (≥50% reduction in seizures for at least 6 months: all randomised patients in the SANTE trail with at least 70 days of diary in the 3 months prior to the annual follow-up visit) (Adapted from Salanova 20158, Sandok 20169)
Significant seizure reductions were observed for specific subgroups, including those with temporal seizure origin and those with or without prior Vagus Nerve Stimulation (VNS) at seven years compared to baseline.
During the blinded phase, DBS was shown to significantly reduce patients' most severe seizures, complex partial seizures, and incidence of epilepsy-related injury.
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.
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.
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:
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:
There were no unanticipated adverse device effects reported in the study.
Device-related adverse event reported through 9 years by ant-dbs-treated patients in the sante study trial (all randomised patients)8
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.
Adverse event rates reported through 7 years by ANT DBS-treated patients in the SANTE trial (all randomised patients)8
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 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.
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 was reported in seven subjects (6.4%) at the time of database cutoff:
There were seven deaths that occurred at the time of the database cutoff:
Including pilot studies, SUDEP rate (definite/probable) was 2.5 per 1,000 patient years including all follow-up.7 Published SUDEP rate for epilepsy surgery candidates is 9.3 per 1,000 patient years.1 The three other deaths were attributed to completed suicide, cardiorespiratory arrest, and liver cancer.7
Medtronic DBS systems are MR Conditional and safe in the MR environment as long as certain conditions are met. If the conditions are not met, a significant risk is tissue lesions from component heating, especially at the lead electrodes, resulting in serious and permanent injury including coma, paralysis, or death. Refer to the MRI Guidelines for Medtronic Deep Brain Stimulation Systems at www.medtronic.com/mri or contact Medtronic at +44 (0) 1923 205101 for a complete list of conditions. Also review current MRI manufacturer labeling before conducting the MRI.
See the device manual for detailed information regarding the instructions for use, indications, contraindications, warnings, precautions, and potential adverse events. For further information, contact your local Medtronic representative and/or consult the Medtronic website at medtronic.eu.
Granbichler C, Oberaigner W, Kuchukhidze G et al. Mortality in adult epilepsy patients decreased over 3 decades: A hospital-based cohort. Epilepsy Curr. 2015;15:214-215.
Granbichler CA, Oberaigner W, Kuchukhidze G et al. Cause-specific mortality in adult epilepsy patients from Tyrol, Austria: Hospital-based study. J Neurol. 2015;262(1):126-133.
Fazel S, Wolf A, Långström N, Newton CR, Lichtenstein P. Premature mortality in epilepsy and the role of psychiatric comorbidity: a total population study. The Lancet 2013;382(9905):1646-1654.
Holst AG, Winkel BG, Risgaard B et al. Epilepsy and risk of death and sudden unexpected death in the young: A nationwide study. Epilepsia. 2013;54(9):1613-1620.
Nevalainen O, Simola M, Ansakorpi H et al. Epilepsy, excess deaths and years of life lost from external causes. Eur J Epidemiol. 2016;31(5):445-453.
Fisher R, Salanova V, Witt T et al. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia. 2010;51(5):899-908.
Medtronic DBS Therapy for Epilepsy Clinical Summary, 2018.
Sandok E, Sperling M, Gross R, Fisher R. Long Term Outcomes of the SANTE Trial: 7-year Follow-up. 2016 Dec 2-2016.
Salanova V, Witt T, Worth R et al. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology. 2015;84(10):1017-1025.
Molnar G. Medtronic registry for epilepsy (MORE). Interim results - baseline data. 69th Annual Meeting American Epilepsy Society. 2015 Dec 4-2015 Dec 8; 2015.
Tröster AI, Meador KJ, Irwin CP, Fisher RS. Memory and mood outcomes after anterior thalamic stimulation for refractory partial epilepsy. Seizure. 2017;45:133-141.