Trial Outcomes & Findings for SANTE - Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (NCT NCT00101933)

NCT ID: NCT00101933

Last Updated: 2018-03-22

Results Overview

A protocol-prespecified generalized estimating equations (GEE) analysis was used to evaluate the treatment effect on seizure frequency. The final GEE model for the primary objective evaluation included treatment effect, log of the baseline seizure count, log of age, visit (categorical), treatment-by-visit interaction (categorical), and the offset (the number of days the diary was recorded in each month).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

157 participants

Primary outcome timeframe

Through the end of the three-month blinded phase

Results posted on

2018-03-22

Participant Flow

157 subjects were enrolled in the study from 11 DEC 2003 through 23 FEB 2007 from 17 centers in US.

47 of 157 subjects exited prior to implant due to not meeting in/exclusion criteria, withdrawal of consent to participate, etc. Of the remaining 110 subjects, 109 subjects were randomized. Those 109 subjects were used for objectives between randomization groups while all 110 implanted subjects were used for long term safety objectives.

Participant milestones

Participant milestones
Measure	Active Stimulation This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.	No Stimulation This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Overall Study STARTED	54	55
Overall Study COMPLETED	54	55
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

SANTE - Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active Stimulation n=54 Participants This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.	No Stimulation n=55 Participants This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.	Total n=109 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	54 Participants n=5 Participants	55 Participants n=7 Participants	109 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	35.2 years STANDARD_DEVIATION 11.1 • n=5 Participants	36.8 years STANDARD_DEVIATION 11.5 • n=7 Participants	36.0 years STANDARD_DEVIATION 11.2 • n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	25 Participants n=7 Participants	54 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	30 Participants n=7 Participants	55 Participants n=5 Participants
Region of Enrollment United States	54 participants n=5 Participants	55 participants n=7 Participants	109 participants n=5 Participants

PRIMARY outcome

Timeframe: Through the end of the three-month blinded phase

Population: This analysis used the protocol-prespecified "Primary analysis data set" which required that subjects had at least 70 days of diary in the blinded phase. One control subject was not included in this analysis as they had 66 of the required 70 days.

Outcome measures

Outcome measures
Measure	Active Stimulation n=54 Participants This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.	No Stimulation n=54 Participants This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Primary Analysis: Change in Seizure Rate	-40.4 Percentage change from baseline Interval -62.9 to -21.6	-14.5 Percentage change from baseline Interval -50.3 to 20.0

PRIMARY outcome

Timeframe: Through the end of the three-month blinded phase

Population: This analysis used the protocol-prespecified "Primary analysis data set" with one additional outlier subject removed from the active group. This subject had 210 stimulation initiated seizures within 48 hours of the device being turned on and was determined to be an outlier using both a statistical and clinical rationale.

A generalized estimating equations (GEE) analysis was used to evaluate the treatment effect on seizure frequency. With one outlier subject removed, the GEE model for this alternative analysis included treatment effect, log of the baseline seizure count, log of age, visit (categorical), and the offset (the number of days the diary was recorded in each month).

Outcome measures

Outcome measures
Measure	Active Stimulation n=53 Participants This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.	No Stimulation n=54 Participants This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Alternative Primary Analysis: Change in Seizure Rate	-35.0 Percentage change from baseline Interval -53.9 to -14.5	-21.1 Percentage change from baseline Interval -51.5 to 7.5

SECONDARY outcome

Timeframe: Through Year 2 of the long-term follow-up phase

Population: This analysis used all subjects who were implanted and received stimulation. One subject was implanted but was not subsequently randomized, but did receive stimulation. This subject has been included for the purposes of this analysis for a total of 110 subjects, as opposed to the 109 stated in the participant flow.

The results are for the follow-up after device implantation through Year 2 and summarized are events that occurred in greater than 5% of subjects. Only events related to the device, therapy, or surgery are included. These abbreviations were used: * General dis...=General disorders and administration site conditions * Injury, poison...=Injury, poisoning and procedural complications * Ther.=Therapeutic. For this summary, adverse events are reported as 'MedDRA System Organ Class - adverse event'.

Outcome measures

Outcome measures
Measure	Active Stimulation n=110 Participants This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.	No Stimulation This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Adverse Events Experienced With the Medtronic DBS System Total # of participants at risk	110 participants	—
Adverse Events Experienced With the Medtronic DBS System Infections and infestations-Implant site infection	10 participants	—
Adverse Events Experienced With the Medtronic DBS System Nervous system disorders-Paresthesia	23 participants	—
Adverse Events Experienced With the Medtronic DBS System Nervous system disorders-Sensory disturbance	8 participants	—
Adverse Events Experienced With the Medtronic DBS System Nervous system disorders-Dizziness	6 participants	—
Adverse Events Experienced With the Medtronic DBS System Nervous system disorders-Memory impairment	7 participants	—
Adverse Events Experienced With the Medtronic DBS System General dis...-Implant site pain	18 participants	—
Adverse Events Experienced With the Medtronic DBS System General dis...-Discomfort	8 participants	—
Adverse Events Experienced With the Medtronic DBS System General dis...-Lead(s) not within target	9 participants	—
Adverse Events Experienced With the Medtronic DBS System General dis...-Implant site inflammation	6 participants	—
Adverse Events Experienced With the Medtronic DBS System Injury, poison...-Post procedural pain	7 participants	—

SECONDARY outcome

Timeframe: Inclusive of all study follow-up after device implantation (mean follow-up 3.7 years)

The number presented is for Definite and Probable SUDEP. The rate is calculated per 1000 subject years of follow-up. The confidence interval is the 95% Poisson confidence interval. Per protocol, only definite and probable SUDEP classifications were included in the calculation. The results shown are for the entire study follow-up after device implantation.

Outcome measures

Outcome measures
Measure	Active Stimulation n=110 Participants This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.	No Stimulation This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Incidence of Sudden Unexplained Death in Epilepsy (SUDEP)	2 Number of subjects experiencing SUDEP Interval 0.6 to 17.79	—

SECONDARY outcome

Timeframe: Through the end of the three-month blinded phase

Population: This analysis used the "Primary analysis data set" which required that subjects had at least 70 days of diary in the blinded phase. One control subject was not included in this analysis as they had 66 of the required 70 days.

A responder is defined as a subject with greater than or equal to 50% reduction in seizures as compared with baseline.

Outcome measures

Outcome measures
Measure	Active Stimulation n=54 Participants This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.	No Stimulation n=54 Participants This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Seizure Responder Rate	16 Number of participants	14 Number of participants

SECONDARY outcome

Timeframe: Through the end of the three-month blinded phase

Population: This analysis used the "Primary analysis data set" which required that subjects had at least 70 days of diary in the blinded phase. In addition, percentage change was not calculated for subjects who had no seizure-free days during the baseline phase.

Difference between active group and control group in percentage change in seizure-free days over the entire blinded phase as compared to the entire baseline phase. The number of seizure-free days was normalized to 84-day baseline and blinded phases for each subject.

Outcome measures

Outcome measures
Measure	Active Stimulation n=50 Participants This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.	No Stimulation n=50 Participants This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Change in Percentage of Days Seizure-free	15.3 Percentage change from baseline Interval 7.6 to 38.3	8.8 Percentage change from baseline Interval -0.5 to 26.5

SECONDARY outcome

Timeframe: Through the end of the three-month blinded phase

Difference between active group and control group in percentage change in the maximum length of seizure-free intervals over the entire blinded phase as compared to the entire baseline phase.

Outcome measures

Outcome measures
Measure	Active Stimulation n=54 Participants This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.	No Stimulation n=54 Participants This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Percentage Change in the Maximum Length of Seizure-free Intervals	35.0 Percentage change from baseline Interval 0.0 to 129.0	24.0 Percentage change from baseline Interval 0.0 to 100.0

SECONDARY outcome

Timeframe: Through the end of the three-month blinded phase

A treatment failure was defined in the protocol as a subject who 1) required 3 or more doses of rescue medication within 48 hours, 3 times during the blinded phase; or 2) had 3 episodes of convulsive status epilepticus during the blinded phase.

Outcome measures

Outcome measures
Measure	Active Stimulation n=54 Participants This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.	No Stimulation n=54 Participants This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Proportion of Treatment Failures	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Through the end of the three-month blinded phase

Population: This analysis used the "Primary analysis data set". In addition, the protocol prespecified that if a subject did not experience the severe seizure in the baseline phase that they would not be included in the calculation of the blinded phase median seizure frequency percentage change from baseline.

Seizures were recorded on daily seizure diaries. The subject recorded the number of seizures by seizure type on the seizure diary. The subject also noted at baseline, of those they had ever experienced, which seizure they considered to be "most severe."

Outcome measures

Outcome measures
Measure	Active Stimulation n=43 Participants This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.	No Stimulation n=38 Participants This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Change in Most Severe Seizures	-39.6 Percentage change from baseline Interval -82.7 to -7.1	-20.4 Percentage change from baseline Interval -50.0 to 29.3

Adverse Events

Active Stimulation

Serious events: 2 serious events

Other events: 42 other events

Deaths: 0 deaths

No Stimulation

Serious events: 6 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Active Stimulation n=54 participants at risk This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.	No Stimulation n=55 participants at risk This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Infections and infestations Implant site infection	0.00% 0/54 • Adverse events were collected throughout the study. The summaries below include events that occurred during the blinded phase. A summary of device related events (operative phase through Year 2) is in the safety characterization objective. Adverse events collected during the blinded phase have been included, regardless of causality. Because the primary purpose of this adverse event summary is to compare the randomization groups, and because the additional non-randomized subject did not have a similar follow-up schedule, the subject has not been included in these analyses.	3.6% 2/55 • Number of events 2 • Adverse events were collected throughout the study. The summaries below include events that occurred during the blinded phase. A summary of device related events (operative phase through Year 2) is in the safety characterization objective. Adverse events collected during the blinded phase have been included, regardless of causality. Because the primary purpose of this adverse event summary is to compare the randomization groups, and because the additional non-randomized subject did not have a similar follow-up schedule, the subject has not been included in these analyses.
Psychiatric disorders Anxiety	0.00% 0/54 • Adverse events were collected throughout the study. The summaries below include events that occurred during the blinded phase. A summary of device related events (operative phase through Year 2) is in the safety characterization objective. Adverse events collected during the blinded phase have been included, regardless of causality. Because the primary purpose of this adverse event summary is to compare the randomization groups, and because the additional non-randomized subject did not have a similar follow-up schedule, the subject has not been included in these analyses.	1.8% 1/55 • Number of events 1 • Adverse events were collected throughout the study. The summaries below include events that occurred during the blinded phase. A summary of device related events (operative phase through Year 2) is in the safety characterization objective. Adverse events collected during the blinded phase have been included, regardless of causality. Because the primary purpose of this adverse event summary is to compare the randomization groups, and because the additional non-randomized subject did not have a similar follow-up schedule, the subject has not been included in these analyses.
Psychiatric disorders Depression	1.9% 1/54 • Number of events 1 • Adverse events were collected throughout the study. The summaries below include events that occurred during the blinded phase. A summary of device related events (operative phase through Year 2) is in the safety characterization objective. Adverse events collected during the blinded phase have been included, regardless of causality. Because the primary purpose of this adverse event summary is to compare the randomization groups, and because the additional non-randomized subject did not have a similar follow-up schedule, the subject has not been included in these analyses.	0.00% 0/55 • Adverse events were collected throughout the study. The summaries below include events that occurred during the blinded phase. A summary of device related events (operative phase through Year 2) is in the safety characterization objective. Adverse events collected during the blinded phase have been included, regardless of causality. Because the primary purpose of this adverse event summary is to compare the randomization groups, and because the additional non-randomized subject did not have a similar follow-up schedule, the subject has not been included in these analyses.
Nervous system disorders Complex partial seizures	0.00% 0/54 • Adverse events were collected throughout the study. The summaries below include events that occurred during the blinded phase. A summary of device related events (operative phase through Year 2) is in the safety characterization objective. Adverse events collected during the blinded phase have been included, regardless of causality. Because the primary purpose of this adverse event summary is to compare the randomization groups, and because the additional non-randomized subject did not have a similar follow-up schedule, the subject has not been included in these analyses.	1.8% 1/55 • Number of events 1 • Adverse events were collected throughout the study. The summaries below include events that occurred during the blinded phase. A summary of device related events (operative phase through Year 2) is in the safety characterization objective. Adverse events collected during the blinded phase have been included, regardless of causality. Because the primary purpose of this adverse event summary is to compare the randomization groups, and because the additional non-randomized subject did not have a similar follow-up schedule, the subject has not been included in these analyses.
Nervous system disorders Muscle contractions involuntary	0.00% 0/54 • Adverse events were collected throughout the study. The summaries below include events that occurred during the blinded phase. A summary of device related events (operative phase through Year 2) is in the safety characterization objective. Adverse events collected during the blinded phase have been included, regardless of causality. Because the primary purpose of this adverse event summary is to compare the randomization groups, and because the additional non-randomized subject did not have a similar follow-up schedule, the subject has not been included in these analyses.	1.8% 1/55 • Number of events 1 • Adverse events were collected throughout the study. The summaries below include events that occurred during the blinded phase. A summary of device related events (operative phase through Year 2) is in the safety characterization objective. Adverse events collected during the blinded phase have been included, regardless of causality. Because the primary purpose of this adverse event summary is to compare the randomization groups, and because the additional non-randomized subject did not have a similar follow-up schedule, the subject has not been included in these analyses.
Nervous system disorders Partial seizures with secondary generalization	0.00% 0/54 • Adverse events were collected throughout the study. The summaries below include events that occurred during the blinded phase. A summary of device related events (operative phase through Year 2) is in the safety characterization objective. Adverse events collected during the blinded phase have been included, regardless of causality. Because the primary purpose of this adverse event summary is to compare the randomization groups, and because the additional non-randomized subject did not have a similar follow-up schedule, the subject has not been included in these analyses.	1.8% 1/55 • Number of events 1 • Adverse events were collected throughout the study. The summaries below include events that occurred during the blinded phase. A summary of device related events (operative phase through Year 2) is in the safety characterization objective. Adverse events collected during the blinded phase have been included, regardless of causality. Because the primary purpose of this adverse event summary is to compare the randomization groups, and because the additional non-randomized subject did not have a similar follow-up schedule, the subject has not been included in these analyses.
Nervous system disorders Status epilepticus	1.9% 1/54 • Number of events 1 • Adverse events were collected throughout the study. The summaries below include events that occurred during the blinded phase. A summary of device related events (operative phase through Year 2) is in the safety characterization objective. Adverse events collected during the blinded phase have been included, regardless of causality. Because the primary purpose of this adverse event summary is to compare the randomization groups, and because the additional non-randomized subject did not have a similar follow-up schedule, the subject has not been included in these analyses.	0.00% 0/55 • Adverse events were collected throughout the study. The summaries below include events that occurred during the blinded phase. A summary of device related events (operative phase through Year 2) is in the safety characterization objective. Adverse events collected during the blinded phase have been included, regardless of causality. Because the primary purpose of this adverse event summary is to compare the randomization groups, and because the additional non-randomized subject did not have a similar follow-up schedule, the subject has not been included in these analyses.

Other adverse events

Additional Information

Jim Vollhaber, Clinical Study Manager

Medtronic Neuromodulation

Phone: 763-526-8093

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The disclosure restrictions on the PI allow for the sponsor to review results communications prior to public release and to embargo communications regarding trial results for a period that is less than or equal to 45 days from the time submitted to sponsor for review. The sponsor is also allowed to require changes for technical correctness and to protect confidential information, copyrightable or patentable material; and when reasonably requested, extend the embargo up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER