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

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ClinicalTrials.gov Identifier: NCT00101933
Recruitment Status : Completed
First Posted : January 19, 2005
Results First Posted : January 21, 2013
Last Update Posted : March 22, 2018
Sponsor:
Information provided by (Responsible Party):
MedtronicNeuro

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Epilepsy
Intervention Device: Medtronic DBS Therapy for epilepsy
Enrollment 157
Recruitment Details 157 subjects were enrolled in the study from 11 DEC 2003 through 23 FEB 2007 from 17 centers in US.
Pre-assignment Details 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.
Arm/Group Title Active Stimulation No Stimulation
Hide Arm/Group Description This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study. This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Period Title: Overall Study
Started 54 55
Completed 54 55
Not Completed 0 0
Arm/Group Title Active Stimulation No Stimulation Total
Hide Arm/Group Description This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study. This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study. Total of all reporting groups
Overall Number of Baseline Participants 54 55 109
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 54 participants 55 participants 109 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
54
 100.0%
55
 100.0%
109
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 54 participants 55 participants 109 participants
35.2  (11.1) 36.8  (11.5) 36.0  (11.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 54 participants 55 participants 109 participants
Female
29
  53.7%
25
  45.5%
54
  49.5%
Male
25
  46.3%
30
  54.5%
55
  50.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 54 participants 55 participants 109 participants
54 55 109
1.Primary Outcome
Title Primary Analysis: Change in Seizure Rate
Hide Description 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).
Time Frame Through the end of the three-month blinded phase
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Stimulation No Stimulation
Hide Arm/Group Description:
This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.
This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Overall Number of Participants Analyzed 54 54
Median (Inter-Quartile Range)
Unit of Measure: Percentage change from baseline
-40.4
(-62.9 to -21.6)
-14.5
(-50.3 to 20.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Stimulation, No Stimulation
Comments The numbers presented are the percentage reduction in the number of seizures in each group. A negative percentage change indicates a seizure reduction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments Since a treatment-by-visit interaction remains in the final model, the results were analyzed by visit. The results shown are for the last month in the blinded phase (month 3-4).
Method Generalized Estimating Equations
Comments This analysis is adjusted for significant baseline covariates.
2.Primary Outcome
Title Alternative Primary Analysis: Change in Seizure Rate
Hide Description 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).
Time Frame Through the end of the three-month blinded phase
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Stimulation No Stimulation
Hide Arm/Group Description:
This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.
This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Overall Number of Participants Analyzed 53 54
Median (Inter-Quartile Range)
Unit of Measure: Percentage change from baseline
-35.0
(-53.9 to -14.5)
-21.1
(-51.5 to 7.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Stimulation, No Stimulation
Comments The numbers presented are the percentage reduction in the number of seizures in each group. A negative percentage change indicates a seizure reduction.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0387
Comments Since a visit-by-treatment interaction did not remain in the final model, the results shown are for the entire blinded phase.
Method Generalized Estimating Equations
Comments This analysis is adjusted for significant baseline covariates.
3.Secondary Outcome
Title Adverse Events Experienced With the Medtronic DBS System
Hide Description

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'.

Time Frame Through Year 2 of the long-term follow-up phase
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title All Implanted Subjects
Hide Arm/Group Description:
This group contains all subjects who were implanted. This includes one additional subject over those that were randomized.
Overall Number of Participants Analyzed 110
Measure Type: Number
Unit of Measure: participants
Total # of participants at risk 110
Infections and infestations-Implant site infection 10
Nervous system disorders-Paresthesia 23
Nervous system disorders-Sensory disturbance 8
Nervous system disorders-Dizziness 6
Nervous system disorders-Memory impairment 7
General dis...-Implant site pain 18
General dis...-Discomfort 8
General dis...-Lead(s) not within target 9
General dis...-Implant site inflammation 6
Injury, poison...-Post procedural pain 7
4.Secondary Outcome
Title Incidence of Sudden Unexplained Death in Epilepsy (SUDEP)
Hide Description

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.

Time Frame Inclusive of all study follow-up after device implantation (mean follow-up 3.7 years)
Hide Outcome Measure Data
Hide Analysis Population Description
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 included in this analysis.
Arm/Group Title All Implanted Subjects
Hide Arm/Group Description:
This group contains all subjects who were implanted. This includes one additional subject over those that were randomized.
Overall Number of Participants Analyzed 110
Measure Type: Number
Unit of Measure: Number of subjects experiencing SUDEP
2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Implanted Subjects
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method No statistical test
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate per 1000 years of stimulation
Estimated Value 4.9
Confidence Interval (2-Sided) 95%
0.60 to 17.79
Estimation Comments The rate is calculated per 1000 subject years of follow-up based on 406 subject years of stimulation. The confidence interval is the 95% Poisson confidence interval. Per protocol, only definite and probable SUDEP were included in the calculation.
5.Secondary Outcome
Title Seizure Responder Rate
Hide Description A responder is defined as a subject with greater than or equal to 50% reduction in seizures as compared with baseline.
Time Frame Through the end of the three-month blinded phase
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Stimulation No Stimulation
Hide Arm/Group Description:
This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.
This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Overall Number of Participants Analyzed 54 54
Measure Type: Number
Unit of Measure: Number of participants
16 14
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Stimulation, No Stimulation
Comments Fisher's Exact test. The numbers presented in this analysis are the number of subjects who were responders based on a responder definition including all subjects with 50% or greater improvement in total seizure count.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.830
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
6.Secondary Outcome
Title Change in Percentage of Days Seizure-free
Hide Description 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.
Time Frame Through the end of the three-month blinded phase
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Stimulation No Stimulation
Hide Arm/Group Description:
This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.
This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Overall Number of Participants Analyzed 50 50
Median (Inter-Quartile Range)
Unit of Measure: Percentage change from baseline
15.3
(7.6 to 38.3)
8.8
(-0.5 to 26.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Stimulation, No Stimulation
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.105
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
7.Secondary Outcome
Title Percentage Change in the Maximum Length of Seizure-free Intervals
Hide Description 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.
Time Frame Through the end of the three-month blinded phase
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Stimulation No Stimulation
Hide Arm/Group Description:
This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.
This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Overall Number of Participants Analyzed 54 54
Median (Inter-Quartile Range)
Unit of Measure: Percentage change from baseline
35.0
(0 to 129)
24.0
(0 to 100)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Stimulation, No Stimulation
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.498
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
8.Secondary Outcome
Title Proportion of Treatment Failures
Hide Description 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.
Time Frame Through the end of the three-month blinded phase
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Stimulation No Stimulation
Hide Arm/Group Description:
This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.
This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Overall Number of Participants Analyzed 54 54
Measure Type: Number
Unit of Measure: participants
0 0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Stimulation, No Stimulation
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
9.Other Pre-specified Outcome
Title Change in Most Severe Seizures
Hide Description 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."
Time Frame Through the end of the three-month blinded phase
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Active Stimulation No Stimulation
Hide Arm/Group Description:
This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study.
This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
Overall Number of Participants Analyzed 43 38
Median (Inter-Quartile Range)
Unit of Measure: Percentage change from baseline
-39.6
(-82.7 to -7.1)
-20.4
(-50.0 to 29.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active Stimulation, No Stimulation
Comments Numbers provided indicate the percentage change from baseline in seizure frequency of each participant's most severe seizures. Negative values indicate improvement from baseline.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.047
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Time Frame 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 Event Reporting Description

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.

 
Arm/Group Title Active Stimulation No Stimulation
Hide Arm/Group Description This group contains subjects who were implanted and randomized to receive active stimulation during the blinded phase of the study. This group contains subjects who were implanted and randomized to receive no stimulation during the blinded phase of the study.
All-Cause Mortality
Active Stimulation No Stimulation
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Active Stimulation No Stimulation
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/54 (3.70%)      6/55 (10.91%)    
Infections and infestations     
Implant site infection * 1  0/54 (0.00%)  0 2/55 (3.64%)  2
Nervous system disorders     
Complex partial seizures * 1  0/54 (0.00%)  0 1/55 (1.82%)  1
Muscle contractions involuntary * 1  0/54 (0.00%)  0 1/55 (1.82%)  1
Partial seizures with secondary generalization * 1  0/54 (0.00%)  0 1/55 (1.82%)  1
Status epilepticus * 1  1/54 (1.85%)  1 0/55 (0.00%)  0
Psychiatric disorders     
Anxiety * 1  0/54 (0.00%)  0 1/55 (1.82%)  1
Depression * 1  1/54 (1.85%)  1 0/55 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (8.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Active Stimulation No Stimulation
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   42/54 (77.78%)      41/55 (74.55%)    
Infections and infestations     
Nasopharyngitis * 1  1/54 (1.85%)  1 5/55 (9.09%)  5
Upper respiratory infection * 1  0/54 (0.00%)  0 4/55 (7.27%)  4
Influenza * 1  3/54 (5.56%)  3 0/55 (0.00%)  0
Injury, poisoning and procedural complications     
Injury * 1  1/54 (1.85%)  1 7/55 (12.73%)  8
Anticonvulsant toxicity * 1  3/54 (5.56%)  3 4/55 (7.27%)  4
Contusion * 1  1/54 (1.85%)  1 4/55 (7.27%)  5
Excoriation * 1  1/54 (1.85%)  1 3/55 (5.45%)  4
Nervous system disorders     
Complex partial seizures * 1  5/54 (9.26%)  5 4/55 (7.27%)  4
Memory impairment * 1  7/54 (12.96%)  7 1/55 (1.82%)  1
Dizziness * 1  3/54 (5.56%)  3 4/55 (7.27%)  4
Headache * 1  2/54 (3.70%)  4 3/55 (5.45%)  3
Paresthesia * 1  5/54 (9.26%)  5 2/55 (3.64%)  2
Partial seizures with secondary generalization * 1  5/54 (9.26%)  5 3/55 (5.45%)  3
Simple partial seizures * 1  3/54 (5.56%)  3 1/55 (1.82%)  1
Psychiatric disorders     
Depression * 1  8/54 (14.81%)  8 1/55 (1.82%)  1
Anxiety * 1  5/54 (9.26%)  5 1/55 (1.82%)  1
Confusional state * 1  4/54 (7.41%)  4 0/55 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (8.0)
No limitations leading to unreliable data were identified.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jim Vollhaber, Clinical Study Manager
Organization: Medtronic Neuromodulation
Phone: 763-526-8093
EMail: medtronicneurotrials@medtronic.com
Layout table for additonal information
Responsible Party: MedtronicNeuro
ClinicalTrials.gov Identifier: NCT00101933    
Other Study ID Numbers: 1604
First Submitted: January 18, 2005
First Posted: January 19, 2005
Results First Submitted: October 1, 2012
Results First Posted: January 21, 2013
Last Update Posted: March 22, 2018