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Trial record 60 of 889 for:    "Depressive Disorder" [DISEASE] AND MADRS

Treatment-Resistant Depression Registry

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00320372
Recruitment Status : Completed
First Posted : May 3, 2006
Results First Posted : December 23, 2015
Last Update Posted : December 23, 2015
Sponsor:
Information provided by (Responsible Party):
Cyberonics, Inc.

Study Type Observational
Study Design Time Perspective: Prospective
Condition Major Depressive Disorder
Enrollment 795
Recruitment Details The TRD Registry was to enroll over a maximum period of 6 years & patients were to be followed for at least 60 months. All sites were to first recruit patients who had agreed to have adjunctive VNS Therapy. Sites were also asked to enroll patients with TRD who would not be implanted with VNS Therapy and would act as a concurrent control group.
Pre-assignment Details A total of 878 subjects were screened in the TRD Registry Study. Thirty-seven were not eligible and 46 were eligible but not treated for various reasons. This left a total of 795 patients in the Safety Population (SP).
Arm/Group Title VNS Therapy Treatment as Usual (TAU)
Hide Arm/Group Description Disposition of study patients from baseline to the end of the study. The VNS Therapy arm, was comprised of D-23 Original patients (Patients that entered the TRD Registry without previous VNS Therapy treatment and selected the VNS Therapy study arm) and D-21 Rollover patients (Patients that entered the TRD Registry, having previously participated in the D-21 study-NCT00305565 and still being treated with VNS Therapy). Disposition of study patients from baseline to the end of the study. The TAU arm were subjects that entered the TRD Registry without previous VNS Therapy treatment and selected the TAU study arm.
Period Title: Overall Study
Started 494 301
VNS Therapy D-23 Original 335 0
VNS Therapy D-21 (NCT00305565) Rollovers 159 0
Completed 299 138
Not Completed 195 163
Reason Not Completed
Physician Decision             4             7
Death             7             8
Withdrawal by Subject             55             37
Non-Compliance             40             39
Did not Meet (I/E)             3             1
Other (i.e. lost to f/u, site closure)             86             71
Arm/Group Title VNS Therapy D-23 Original VNS Therapy D-21 Rollover Treatment as Usual (TAU) Total
Hide Arm/Group Description Subjects that entered the TRD Registry without previous VNS Therapy treatment and selected the VNS Therapy study arm. Subjects that entered the TRD Registry, having previously participated in the D-21 study and still being treated with VNS Therapy treatment were included within the VNS Therapy group. Based on the duration from initial implant to enrollment date, the D-21 rollover patients entered at the appropriate D-23 follow-up interval (i.e., patient enrolls at 24 months post implant for their first D-23 follow up visit. This 24 month visit corresponds to the 24 month follow up in the TRD Registry). Starting with the first TRD Registry visit, the D-21 long-term patients were to follow the same data collection schedule as other Original VNS and TAU Registry patients. Non-VNS Patients - Treatment-resistant depression patients not receiving VNS Therapy. Subjects that entered the TRD Registry without previous VNS Therapy treatment and selected the TAU study arm. Total of all reporting groups
Overall Number of Baseline Participants 335 159 301 795
Hide Baseline Analysis Population Description
A total of 878 subjects were screened. Thirty-seven were not eligible and 46 were eligible but not treated for various reasons. This left a total of 795 patients in the Safety Population (SP). The total number of patients in each group may be lower than SP if there was missing D-21 assessment data, as D-21 baseline data was not identical to D-23.
Age, Customized  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 335 participants 159 participants 301 participants 795 participants
Age at Baseline (n=335, n=159, n=301) 48.9  (10.41) 48.9  (9.51) 49.9  (11.07) 49.3  (10.49)
Age-Initial Onset of Depression(n=334,n=159,n=301) 20.8  (12.13) 21.1  (11.11) 21.1  (11.40) 21.0  (11.64)
Age-Initial Dx. of Depression(n=334,n=159,n=301) 29.0  (10.95) 28.6  (10.50) 29.5  (11.89) 29.1  (11.22)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 335 participants 159 participants 301 participants 795 participants
Female
231
  69.0%
119
  74.8%
211
  70.1%
561
  70.6%
Male
104
  31.0%
40
  25.2%
90
  29.9%
234
  29.4%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 335 participants 159 participants 301 participants 795 participants
Caucasian 323 155 274 752
African-American 4 4 6 14
Hispanic 3 0 19 22
Asian 2 0 1 3
Other 3 0 1 4
[1]
Measure Description: Ethnic Orgin of participants in the study
Lifetime Episodes of Depression Diagnosed (n=335, n=0, n=301)  
Mean (Standard Deviation)
Unit of measure:  Lifetime Episodes of Depression
Number Analyzed 335 participants 159 participants 301 participants 795 participants
14.9  (24.14) NA [1]   (NA) 12.0  (23.86) 13.5  (24.03)
[1]
This Variable was captured as categorical variable as part of D-21 study
Number of Failed Treatments (n=335, n=159, n=301)  
Mean (Standard Deviation)
Unit of measure:  Number of Failed Treatments
Number Analyzed 335 participants 159 participants 301 participants 795 participants
8.0  (3.05) 8.6  (3.74) 7.3  (2.92) 7.9  (3.19)
Suicide Attempts in Lifetime (n=335, n=159, n=301)  
Mean (Standard Deviation)
Unit of measure:  Number of Suicide Attempts in a Lifetime
Number Analyzed 335 participants 159 participants 301 participants 795 participants
2.1  (4.38) 1.2  (2.95) 1.2  (2.41) 1.6  (3.49)
Diagnosis Disorder (Major Depressive Disorder (MDD) or Bipolar Disorder (BPD)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 335 participants 159 participants 301 participants 795 participants
MDD, Recurrent, Moderate Severity 42 21 69 132
MDD, Recurrent, Severe w/o Psychotic Features 135 90 95 320
MDD, Single Episode, Moderate Severity 12 4 30 46
MDD, Single Episode, Severe w/o Psychotic Features 49 7 36 92
BPD I, MRE Depressed, Moderate Severity 19 6 21 46
BPD I, MRE Depressed,Severe w/o Psychotic Features 46 16 12 74
BPD II, MRE Depressed 32 15 38 85
1.Primary Outcome
Title Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline)
Hide Description

Response Rate was computed and summarized as the proportion of patients that achieved ≥ 50% reduction from baseline in MADRS total score at each post-baseline visit. The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The lower a score the less symptom severity is seen. A patient was considered a “Responder” (Yes = 1) if achieved ≥ 50% reduction from baseline in MADRS total score at visit month assessment post-baseline. A “Non-Responder” (No = 0) was any patient who did not achieve ≥ 50% reduction from baseline in MADRS score at visit month assessment post-baseline.

Total number of patients in each group may be lower than ITT in a case of missing assessment data.

Time Frame 3-Month Through 60-Month (Post Baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat (ITT) Population: VNS Therapy Population (n=489 (D-23=330 + D-21=159)) + (n= 276) TAU population
Arm/Group Title VNS Therapy Treatment As Usual (TAU)
Hide Arm/Group Description:
MADRS % Responders (Percentage of Responders)
MADRS % Responders (Percentage of Responders)
Overall Number of Participants Analyzed 489 276
Measure Type: Number
Unit of Measure: Percentage of Participants
3-Month (n=454, n=249) 24 8.8
6-Month (n=432, n=224) 28 13.8
9-Month (n=408, n=193) 33.8 13.5
12-Month (n=403, n=194) 38.2 17.5
18-Month (n=223, n=162) 34.1 15.4
24-Month (n=233, n=146) 38.6 18.5
30-Month (n=224, n=138) 34.8 22.5
36-Month (n=245, n=133) 38.8 17.3
42-Month (n=245, n=121) 41.2 19.0
48-Month (n=246, n=109) 46.3 22.0
54-Month (n=222, n=102) 48.2 27.5
60-Month (n=250, n=116) 49.6 25.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection VNS Therapy
Comments Null Hypothesis: Percentage of responders across groups is the same. Alternate Hypothesis: Percentage of responders across groups is different.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter MMRM Least Squares Mean
Estimated Value 38.1
Confidence Interval (2-Sided) 95%
36.3 to 39.9
Estimation Comments Mixed Model Repeated Measure analysis on MADRS responders (binary variable with 1=yes, 0=no) as the response variable in the model. The covariates are treatment, visit and propensity quintile. This analysis of covariance produced least square means.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment As Usual (TAU)
Comments Null Hypothesis: Percentage of responders across groups is the same. Alternate Hypothesis: Percentage of responders across groups is different.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter MMRM Least Squares Mean
Estimated Value 17.0
Confidence Interval (2-Sided) 95%
15.2 to 19.0
Estimation Comments Mixed Model Repeated Measure analysis on MADRS responders (binary variable with 1=yes, 0=no) as the response variable in the model. The covariates are treatment, visit and propensity quintile. This analysis of covariance produced least square means.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection VNS Therapy, Treatment As Usual (TAU)
Comments Null Hypothesis: Percentage of responders across groups is the same. Alternate Hypothesis: Percentage of responders across groups is different.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
2.Secondary Outcome
Title Time Until Recurrence (TUR) for Patients That Achieved Remission, Based on Montgomery Asberg Depression Rating Scale (MADRS)
Hide Description

Recurrence based on MADRS is defined as first time attained MADRS total score ≥ 20 after achieving remission. Remission is a binary outcome response variable (Yes/No in-remission) defined as MADRS total score </= 9 at visit month assessment post-baseline. Duration of remission Computed as recorded date of the first recurrence/relapse (MADRS score >/= 20) minus the recorded date of first achieved remission (MADRS score </=9). Only a subpopulation that achieved remission will be included in the summary.

Time-to-event analyses were summarized using Kaplan-Meier curves. Patients who did not achieve recurrence at the end of the study were censored on the last visit date recorded. Additionally, patients who discontinued early were censored on last date of contact. Censored observations and confidence intervals for the estimated median times were calculated.

Time Frame 3-Month Through 60-Month (Post Baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat (ITT) Population: VNS Therapy Population (n=489 (D-23=330 + D-21=159)) + (n= 276) TAU population
Arm/Group Title VNS Therapy Treatment As Usual (TAU)
Hide Arm/Group Description:
Time until recurrence based on the MADRS
Time until recurrence based on the MADRS
Overall Number of Participants Analyzed 204 70
Overall Number of Units Analyzed
Type of Units Analyzed: Censored Patients
151 46
Median (95% Confidence Interval)
Unit of Measure: Months
1st Quartile (25%);Time (Mo.) Until Recurrence
14
(10 to 19)
9
(6 to 13)
Kaplan-Meier Median;Time (Mo.) Until Recurrence
40 [1] 
(26 to NA)
19 [2] 
(10 to NA)
[1]
Unable to compute based on Kaplan Meier Calculation due to too few events
[2]
Unable to compute based on Kaplan Meier Calculation due to too few events.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection VNS Therapy, Treatment As Usual (TAU)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1015
Comments Comparison for Kaplan Meier Median Time until recurrence
Method Log Rank
Comments Null hypothesis: median TUR between 2 groups is not different. Alternate hypothesis: median TUR between 2 groups is different.
3.Secondary Outcome
Title Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline)
Hide Description Remission is a binary outcome response variable (Yes/No Inremission) defined as MADRS total score < 9 at visit month assessment post-baseline. The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The lower a score the less symptom severity is seen and in general it is accepted that a score between 0-6 is indicative of a normal/symptom-free individual; 7-19 is indicative of a patient with mild depression; 20-34 is indicative of a patient with moderate depression; and >34 is indicative of a patient with severe depression. Total number of patients in each group may be lower than ITT in a case of missing assessment data.
Time Frame 3-Month Through 60-Month (Post Baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat (ITT) Population: VNS Therapy Population (n=489 (D-23=330 + D-21=159)) + (n= 276) TAU population
Arm/Group Title VNS Therapy Treatment As Usual (TAU)
Hide Arm/Group Description:
MADRS % Remitters (Percentage of Subjects in Remission)
MADRS % Remitters (Percentage of Subjects in Remission)
Overall Number of Participants Analyzed 489 276
Measure Type: Number
Unit of Measure: Percentage of Participants
3-Month (n=454, n=249) 8.6 2.8
6-Month (n=432, n=224) 15 6.3
9-Month (n=408, n=193) 16.2 5.7
12-Month (n=403, n=194) 19.4 8.2
18-Month (n=223, n=162) 14.3 7.4
24-Month (n=233, n=146) 21.9 11
30-Month (n=224, n=138) 20.5 12.3
36-Month (n=245, n=133) 19.2 11.3
42-Month (n=245, n=121) 24.9 13.2
48-Month (n=246, n=109) 25.6 14.7
54-Month (n=222, n=102) 28.4 13.7
60-Month (n=250, n=116) 27.6 19
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection VNS Therapy
Comments Null Hypothesis: Percentage of remitters across groups is the same. Alternate Hypothesis: Percentage of remitters across groups is different.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter MMRM Least Squares Mean
Estimated Value 19.8
Confidence Interval (2-Sided) 95%
18.4 to 21.3
Estimation Comments Mixed Model Repeated Measure analysis on MADRS remitters (binary variable with 1=yes, 0=no) as the response variable in the model. The covariates are treatment, visit and propensity quintile. This analysis of covariance produced least square means.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Treatment As Usual (TAU)
Comments Null Hypothesis: Percentage of remitters across groups is the same. Alternate Hypothesis: Percentage of remitters across groups is different.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter MMRM Least Squares Mean
Estimated Value 8.1
Confidence Interval (2-Sided) 95%
6.9 to 9.5
Estimation Comments Mixed Model Repeated Measure analysis on MADRS remitters (binary variable with 1=yes, 0=no) as the response variable in the model. The covariates are treatment, visit and propensity quintile. This analysis of covariance produced least square means.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection VNS Therapy, Treatment As Usual (TAU)
Comments Null Hypothesis: Percentage of responders across groups is the same. Alternate Hypothesis: Percentage of responders across groups is different.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
4.Secondary Outcome
Title Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation
Hide Description

This assessment was completed telephonically by a third party rater (Central Rater Group). The rating was based on a clinical interview moving from broadly phrased questions about symptoms to more detailed ones, which allowed a precise rating of severity. The rater decided whether the rating lied on the defined scale steps (0, 2, 4, 6) or between them (1, 3, 5) and then checked the appropriate selection on the MADRS Item 10 Suicidal Thoughts (Ideation).

Total number of patients analyzed may be lower than ITT in a case of missing assessment data.

Time Frame 1 Week Pre-Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
D-23 Original + TAU [(n= 330) + (n= 276)] minus 2 missing assessment data. These risk factors assessed at baseline and pre-baseline were not collected with respect to treatment, therefore this information is not presented by treatment arm.
Arm/Group Title ITT Population
Hide Arm/Group Description:
VNS Therapy and Treatment as Usual (TAU)
Overall Number of Participants Analyzed 763
Measure Type: Number
Unit of Measure: Percentage of Patients
0 Enjoys Life 6.03
1 28.83
2 Weary of Life 25.56
3 18.87
4 Probably Better Off Dead 14.81
5 4.72
6 Explicit Plans for Suicide 1.18
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ITT Population
Comments The statistical modeling of predictors of suicide attempts and suicidal ideations considered 15 variables, defined in the protocol a priori to determine which ones were predictive of suicide attempts and suicidal ideations. Four variables representing the baseline disease and patient factors were considered predictors of suicidality. This outcome measure presents the underlying data collected and the corresponding correlation coefficient for one of the 4 variables identified.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments

Null hypothesis: There is a correlation between MADRS follow-up suicidal thoughts and baseline suicidal thoughts.

Alternate hypothesis: There is no correlation between MADRS follow-up suicidal thoughts and baseline suicidal thoughts.

Method Pearson Correlation Coefficients
Comments [Not Specified]
Method of Estimation Estimation Parameter Pearson Correlation Coefficients
Estimated Value .34997
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture
Hide Description

This assessment was completed by the physician at the baseline visit in a clinical interview. The physician decided which category (as shown in outcome measure data table) best characterized the patient's medical threat to life of their most recent suicidal gesture or attempt.

Total number of patients analyzed may be lower than ITT in a case of missing assessment data.

Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
D-23 Original + TAU [(n= 330) + (n= 276)] minus 159 missing assessment data. These risk factors assessed at baseline and pre-baseline were not collected with respect to treatment, therefore this information is not presented by treatment arm.
Arm/Group Title ITT Population
Hide Arm/Group Description:
VNS Therapy and Treatment as Usual (TAU)
Overall Number of Participants Analyzed 606
Measure Type: Number
Unit of Measure: Percentage of Patients
Patient Never Made an Attempt 46.70
No Information or Not Sure 3.14
No Danger 5.61
Minimal 3.47
Mild 8.91
Moderate 18.15
Severe 11.39
Extreme 2.64
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ITT Population
Comments The statistical modeling of predictors of suicide attempts and suicidal ideations considered 15 variables, defined in the protocol a priori to determine which ones were predictive of suicide attempts and suicidal ideations. Four variables representing the baseline disease and patient factors were considered predictors of suicidality. This outcome measure presents the underlying data collected and the corresponding correlation coefficient for one of the 4 variables identified.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments

Null hypothesis: There is a correlation between MADRS follow-up suicidal thoughts and baseline medical threat to life.

Alternate hypothesis: There is no correlation between MADRS follow-up suicidal thoughts and baseline medical threat to life.

Method Pearson Correlation Coefficients
Comments [Not Specified]
Method of Estimation Estimation Parameter Pearson Correlation Coefficients
Estimated Value .14837
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture
Hide Description

This assessment was completed by the physician at the baseline visit in a clinical interview. The physician decided which category (as shown in outcome measure data table) best characterized the patient's intent of their most recent suicidal gesture or attempt.

Total number of patients analyzed may be lower than ITT in a case of missing assessment data.

Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
D-23 Original + TAU [(n= 330) + (n= 276)] minus 159 missing assessment data. These risk factors assessed at baseline and pre-baseline were not collected with respect to treatment, therefore this information is not presented by treatment arm.
Arm/Group Title ITT Population
Hide Arm/Group Description:
VNS Therapy and Treatment as Usual (TAU)
Overall Number of Participants Analyzed 606
Measure Type: Number
Unit of Measure: Percentage of Patients
Patient Never Made an Attempt 46.86
No Information or Not Sure 3.80
Obviously no Intent 2.31
Not Sure or Only Minimal Intent 5.12
Definite But Very Ambivalent 11.06
Serious 12.05
Very Serious 9.57
Extreme 9.24
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ITT Population
Comments The statistical modeling of predictors of suicide attempts and suicidal ideations considered 15 variables, defined in the protocol a priori to determine which ones were predictive of suicide attempts and suicidal ideations. Four variables representing the baseline disease and patient factors were considered predictors of suicidality. This outcome measure presents the underlying data collected and the corresponding correlation coefficient for one of the 4 variables identified.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments

Null hypothesis: There is a correlation between MADRS f/u suicidal thoughts and baseline intent of suicidal gesture.

Alternate hypothesis: There is no correlation between MADRS f/u suicidal thoughts and baseline intent of suicidal gesture.

Method Pearson Correlation Coefficients
Comments [Not Specified]
Method of Estimation Estimation Parameter Pearson Correlation Coefficients
Estimated Value .14819
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE
Hide Description This assessment was completed by the physician at the screening visit. The physician decided which DSM-IV Diagnosis (as shown in outcome measure data table) best characterized the patient's primary diagnosis of MDE.
Time Frame Screening
Hide Outcome Measure Data
Hide Analysis Population Description
D-23 Original + TAU [(n= 330) + (n= 276)]. These risk factors assessed at baseline and pre-baseline were not collected with respect to treatment, therefore this information is not presented by treatment arm.
Arm/Group Title ITT Population
Hide Arm/Group Description:
VNS Therapy and Treatment as Usual (TAU)
Overall Number of Participants Analyzed 765
Measure Type: Number
Unit of Measure: Percentage of Patients
MDD, Recurrent, Moderate Severity 16.99
MDD, Recurrent, Severe w/o Psychotic Features 40.39
MDD, Single Episode, Moderate Severity 5.88
MDD, Single Episode, Severe w/o Psychotic Features 11.24
BPD I, MRE Depressed, Moderate Severity 5.75
BPD I, MRE Depressed,Severe w/o Psychotic Features 9.41
BPD II, MRE Depressed 10.33
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ITT Population
Comments The statistical modeling of predictors of suicide attempts and suicidal ideations considered 15 variables, defined in the protocol a priori to determine which ones were predictive of suicide attempts and suicidal ideations. Four variables representing the baseline disease and patient factors were considered predictors of suicidality. This outcome measure presents the underlying data collected and the corresponding correlation coefficient for one of the 4 variables identified.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0012
Comments

Null hypothesis: There is a correlation between MADRS follow-up suicidal thoughts and baseline primary diagnosis of MDE.

Alternate hypothesis: There is no correlation between MADRS follow-up suicidal thoughts and baseline primary diagnosis of MDE.

Method Pearson Correlation Coefficients
Comments [Not Specified]
Method of Estimation Estimation Parameter Pearson Correlation Coefficients
Estimated Value .04625
Estimation Comments [Not Specified]
8.Post-Hoc Outcome
Title Mortality and Suicidality in Safety Population (Total Number of Deaths)
Hide Description The number of deaths on the study were collected from the baseline visit.
Time Frame 3-Month (baseline or implantation) Through 60-Month (Post Baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population
Arm/Group Title VNS Therapy Treatment as Usual (TAU)
Hide Arm/Group Description:
VNS Patients - Treatment-resistant depression patients treated with VNS Therapy
Non-VNS Patients - Treatment-resistant depression patients not receiving VNS Therapy
Overall Number of Participants Analyzed 494 301
Measure Type: Number
Unit of Measure: Number of Deaths
7 8
9.Post-Hoc Outcome
Title Mortality and Suicidality in Safety Population (Total Patient Years Exposed)
Hide Description Treatment exposure time in years for all patients for all treatment groups were calculated in 1000 person year measure.
Time Frame 3-Month Through 60-Month (Post Baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population
Arm/Group Title VNS Therapy Treatment as Usual (TAU)
Hide Arm/Group Description:
VNS Patients - Treatment-resistant depression patients treated with VNS Therapy
Non-VNS Patients - Treatment-resistant depression patients not receiving VNS Therapy
Overall Number of Participants Analyzed 494 301
Measure Type: Number
Unit of Measure: Exposure Per 1000 Patient Years
1985.083 926.493
10.Post-Hoc Outcome
Title Mortality and Suicidality in Safety Population (All-Cause Mortality/1000 Person Years)
Hide Description All cause mortality is defined as the number of deaths per calculated 1000 person years.
Time Frame 3-Month Through 60-Month (Post Baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population
Arm/Group Title VNS Therapy Treatment as Usual (TAU)
Hide Arm/Group Description:
VNS Patients - Treatment-resistant depression patients treated with VNS Therapy
Non-VNS Patients - Treatment-resistant depression patients not receiving VNS Therapy
Overall Number of Participants Analyzed 494 301
Measure Type: Number
Unit of Measure: Deaths Per 1000 Person Years
3.53 8.63
11.Post-Hoc Outcome
Title Mortality and Suicidality in Safety Population (Number of Suicides)
Hide Description The number suicides on the study were collected from the baseline visit.
Time Frame 3-Month Through 60-Month (Post Baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population
Arm/Group Title VNS Therapy Treatment as Usual (TAU)
Hide Arm/Group Description:
VNS Patients - Treatment-resistant depression patients treated with VNS Therapy
Non-VNS Patients - Treatment-resistant depression patients not receiving VNS Therapy
Overall Number of Participants Analyzed 494 301
Measure Type: Number
Unit of Measure: Number of Suicides
2 2
12.Post-Hoc Outcome
Title Mortality and Suicidality in Safety Population (Suicides/1000 Person Years)
Hide Description The number of suicides per calculated 1000 person years.
Time Frame 3-Month Through 60-Month (Post Baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population
Arm/Group Title VNS Therapy Treatment as Usual (TAU)
Hide Arm/Group Description:
VNS Patients - Treatment-resistant depression patients treated with VNS Therapy
Non-VNS Patients - Treatment-resistant depression patients not receiving VNS Therapy
Overall Number of Participants Analyzed 494 301
Measure Type: Number
Unit of Measure: Number of Suicides Per 1000 Person Years
1.01 2.20
13.Post-Hoc Outcome
Title Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month
Hide Description The Q-LES-Q-SF is a self-report scale to assess the degree of enjoyment and satisfaction experienced by the patient during the past week. There are 2 forms of this instrument: the short form and the long form. The short form employs the 14 general activities included in the long form, as well as 2 global items. Five-point item scores (1 to 5) are aggregated, with higher scores indicative of greater enjoyment or satisfaction in each domain. The scoring of the Q-LESQ-SF involves summing only the first 14 items to yield a raw total score. The last 2 items are not included in the total score but stand alone. The raw total score ranges from 14 (worst score) to 70 (best score). Higher Q-LES-QSF score indicates more enjoyment and satisfaction (Endicott, Nee et al. 1993).
Time Frame 3-Month Through 60-Month (Post Baseline)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population minus D-21 Subjects: VNS Therapy Population (D-23=330) + (n= 276) TAU population. The total number of patients in each group is lower than ITT due to missing assessment data, for which a large portion is that of D-21 subjects. The Q-LES-Q-SF was not collected in the D-21 Study.
Arm/Group Title VNS Therapy Treatment As Usual (TAU)
Hide Arm/Group Description:
Change from Baseline Score
Change from Baseline Score
Overall Number of Participants Analyzed 330 276
Mean (Standard Deviation)
Unit of Measure: units on a scale
3 Months (n=322, n=261) 7.92  (16.20) 1.38  (16.61)
6 Months (n=298, n=239) 9.11  (15.66) 4.36  (17.46)
9 Months (n=270, n=216) 10.50  (16.74) 3.97  (17.07)
12 Months (n=266, n=211) 11.04  (18.36) 5.49  (17.56)
18 Months (n=264, n=179) 11.40  (18.29) 3.88  (16.03)
24 Months (n=240, n=159) 13.15  (18.13) 7.50  (16.73)
30 Months (n=223, n=147) 13.06  (18.63) 8.13  (16.73)
36 Months (n=219, n=149) 15.59  (18.43) 8.34  (16.11)
42 Months (n=196, n=141) 14.67  (17.46) 8.55  (17.95)
48 Months (n=179, n=127) 14.70  (19.02) 9.88  (17.28)
54 Months (n=156, n=128) 16.44  (18.63) 10.49  (16.74)
60 Months (n=173, n=136) 17.20  (17.59) 10.11  (17.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection VNS Therapy, Treatment As Usual (TAU)
Comments 3 Month Time point
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments

Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.

Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.

Method F-Test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection VNS Therapy, Treatment As Usual (TAU)
Comments 6 Month Time point
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0068
Comments

Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.

Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.

Method F-Test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection VNS Therapy, Treatment As Usual (TAU)
Comments 9 Month Time point
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0008
Comments

Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.

Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.

Method F-Test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection VNS Therapy, Treatment As Usual (TAU)
Comments 12 Month Time point
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0003
Comments

Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.

Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.

Method F-Test
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection VNS Therapy, Treatment As Usual (TAU)
Comments 18 Month Time point
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments

Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.

Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.

Method F-Test
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection VNS Therapy, Treatment As Usual (TAU)
Comments 24 Month Time point
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0059
Comments

Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.

Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.

Method F-Test
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection VNS Therapy, Treatment As Usual (TAU)
Comments 30 Month Time point
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0028
Comments

Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.

Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.

Method F-Test
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection VNS Therapy, Treatment As Usual (TAU)
Comments 36 Month Time point
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0002
Comments

Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.

Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.

Method F-Test
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection VNS Therapy, Treatment As Usual (TAU)
Comments 42 Month Time point
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0051
Comments

Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.

Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.

Method F-Test
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection VNS Therapy, Treatment As Usual (TAU)
Comments 48 Month Time point
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0363
Comments

Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.

Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.

Method F-Test
Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection VNS Therapy, Treatment As Usual (TAU)
Comments 54 Month Time point
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0048
Comments

Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.

Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.

Method F-Test
Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection VNS Therapy, Treatment As Usual (TAU)
Comments 60 Month Time point
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0009
Comments

Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.

Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.

Method F-Test
Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection VNS Therapy
Comments

Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.

Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter MMRM Least Squares Mean
Estimated Value 12.1009
Confidence Interval (2-Sided) 95%
10.8979 to 13.3039
Estimation Comments Mixed Model Repeated Measure analysis on Q-LES-Q change from baseline score (continuous var) as the response variable in the model. The covariates are treatment, visit and propensity quintile. This analysis of covariance produced least square means.
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Treatment As Usual (TAU)
Comments

Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.

Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter MMRM Least Squares Mean
Estimated Value 7.5964
Confidence Interval (2-Sided) 95%
6.1327 to 9.0602
Estimation Comments Mixed Model Repeated Measure analysis on Q-LES-Q change from baseline score (continuous var) as the response variable in the model. The covariates are treatment, visit and propensity quintile. This analysis of covariance produced least square means.
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection VNS Therapy, Treatment As Usual (TAU)
Comments

Null Hypothesis: Difference between change from baseline value of two treatment groups equals zero.

Alternate Hypothesis: Difference between change from baseline value of two treatment groups is not equal to zero.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Time Frame N/A (Adverse event information was not collected as part of the TRD Registry Protocol)
Adverse Event Reporting Description Physicians were instructed to notify Cyberonics' Clinical Technical Support (CTS) department of all Medical Devices Reporting (MDR) events that occurred in TRD Registry participants receiving VNS Therapy.
 
Arm/Group Title Safety Events
Hide Arm/Group Description N/A (not collected)
All-Cause Mortality
Safety Events
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Safety Events
Affected / at Risk (%)
Total   0/0 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Safety Events
Affected / at Risk (%)
Total   0/0 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Mark Bunker, PharmD, Sr. Director, Global Medical Affairs
Organization: Cyberonics, Inc
Phone: 281-228-7223
EMail: mark.bunker@cyberonics.com
Layout table for additonal information
Responsible Party: Cyberonics, Inc.
ClinicalTrials.gov Identifier: NCT00320372     History of Changes
Obsolete Identifiers: NCT00657215
Other Study ID Numbers: TRD Registry
First Submitted: May 1, 2006
First Posted: May 3, 2006
Results First Submitted: December 18, 2015
Results First Posted: December 23, 2015
Last Update Posted: December 23, 2015