Trial Outcomes & Findings for Treatment-Resistant Depression Registry (NCT NCT00320372)
NCT ID: NCT00320372
Last Updated: 2015-12-23
Results Overview
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.
COMPLETED
795 participants
3-Month Through 60-Month (Post Baseline)
2015-12-23
Participant Flow
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.
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).
Participant milestones
| Measure |
VNS Therapy
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).
|
Treatment as Usual (TAU)
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.
|
|---|---|---|
|
Overall Study
STARTED
|
494
|
301
|
|
Overall Study
VNS Therapy D-23 Original
|
335
|
0
|
|
Overall Study
VNS Therapy D-21 (NCT00305565) Rollovers
|
159
|
0
|
|
Overall Study
COMPLETED
|
299
|
138
|
|
Overall Study
NOT COMPLETED
|
195
|
163
|
Reasons for withdrawal
| Measure |
VNS Therapy
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).
|
Treatment as Usual (TAU)
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.
|
|---|---|---|
|
Overall Study
Physician Decision
|
4
|
7
|
|
Overall Study
Death
|
7
|
8
|
|
Overall Study
Withdrawal by Subject
|
55
|
37
|
|
Overall Study
Non-Compliance
|
40
|
39
|
|
Overall Study
Did not Meet (I/E)
|
3
|
1
|
|
Overall Study
Other (i.e. lost to f/u, site closure)
|
86
|
71
|
Baseline Characteristics
Treatment-Resistant Depression Registry
Baseline characteristics by cohort
| Measure |
VNS Therapy D-23 Original
n=335 Participants
Subjects that entered the TRD Registry without previous VNS Therapy treatment and selected the VNS Therapy study arm.
|
VNS Therapy D-21 Rollover
n=159 Participants
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.
|
Treatment as Usual (TAU)
n=301 Participants
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
n=795 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
Age at Baseline (n=335, n=159, n=301)
|
48.9 Years
STANDARD_DEVIATION 10.41 • n=5 Participants
|
48.9 Years
STANDARD_DEVIATION 9.51 • n=7 Participants
|
49.9 Years
STANDARD_DEVIATION 11.07 • n=5 Participants
|
49.3 Years
STANDARD_DEVIATION 10.49 • n=4 Participants
|
|
Age, Customized
Age-Initial Onset of Depression(n=334,n=159,n=301)
|
20.8 Years
STANDARD_DEVIATION 12.13 • n=5 Participants
|
21.1 Years
STANDARD_DEVIATION 11.11 • n=7 Participants
|
21.1 Years
STANDARD_DEVIATION 11.40 • n=5 Participants
|
21.0 Years
STANDARD_DEVIATION 11.64 • n=4 Participants
|
|
Age, Customized
Age-Initial Dx. of Depression(n=334,n=159,n=301)
|
29.0 Years
STANDARD_DEVIATION 10.95 • n=5 Participants
|
28.6 Years
STANDARD_DEVIATION 10.50 • n=7 Participants
|
29.5 Years
STANDARD_DEVIATION 11.89 • n=5 Participants
|
29.1 Years
STANDARD_DEVIATION 11.22 • n=4 Participants
|
|
Sex: Female, Male
Female
|
231 Participants
n=5 Participants
|
119 Participants
n=7 Participants
|
211 Participants
n=5 Participants
|
561 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
104 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
90 Participants
n=5 Participants
|
234 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
323 Participants
n=5 Participants
|
155 Participants
n=7 Participants
|
274 Participants
n=5 Participants
|
752 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
African-American
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Lifetime Episodes of Depression Diagnosed (n=335, n=0, n=301)
|
14.9 Lifetime Episodes of Depression
STANDARD_DEVIATION 24.14 • n=5 Participants
|
NA Lifetime Episodes of Depression
STANDARD_DEVIATION NA • n=7 Participants
|
12.0 Lifetime Episodes of Depression
STANDARD_DEVIATION 23.86 • n=5 Participants
|
13.5 Lifetime Episodes of Depression
STANDARD_DEVIATION 24.03 • n=4 Participants
|
|
Number of Failed Treatments (n=335, n=159, n=301)
|
8.0 Number of Failed Treatments
STANDARD_DEVIATION 3.05 • n=5 Participants
|
8.6 Number of Failed Treatments
STANDARD_DEVIATION 3.74 • n=7 Participants
|
7.3 Number of Failed Treatments
STANDARD_DEVIATION 2.92 • n=5 Participants
|
7.9 Number of Failed Treatments
STANDARD_DEVIATION 3.19 • n=4 Participants
|
|
Suicide Attempts in Lifetime (n=335, n=159, n=301)
|
2.1 Number of Suicide Attempts in a Lifetime
STANDARD_DEVIATION 4.38 • n=5 Participants
|
1.2 Number of Suicide Attempts in a Lifetime
STANDARD_DEVIATION 2.95 • n=7 Participants
|
1.2 Number of Suicide Attempts in a Lifetime
STANDARD_DEVIATION 2.41 • n=5 Participants
|
1.6 Number of Suicide Attempts in a Lifetime
STANDARD_DEVIATION 3.49 • n=4 Participants
|
|
Diagnosis Disorder (Major Depressive Disorder (MDD) or Bipolar Disorder (BPD)
MDD, Recurrent, Moderate Severity
|
42 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
69 Participants
n=5 Participants
|
132 Participants
n=4 Participants
|
|
Diagnosis Disorder (Major Depressive Disorder (MDD) or Bipolar Disorder (BPD)
MDD, Recurrent, Severe w/o Psychotic Features
|
135 Participants
n=5 Participants
|
90 Participants
n=7 Participants
|
95 Participants
n=5 Participants
|
320 Participants
n=4 Participants
|
|
Diagnosis Disorder (Major Depressive Disorder (MDD) or Bipolar Disorder (BPD)
MDD, Single Episode, Moderate Severity
|
12 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
46 Participants
n=4 Participants
|
|
Diagnosis Disorder (Major Depressive Disorder (MDD) or Bipolar Disorder (BPD)
MDD, Single Episode, Severe w/o Psychotic Features
|
49 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
92 Participants
n=4 Participants
|
|
Diagnosis Disorder (Major Depressive Disorder (MDD) or Bipolar Disorder (BPD)
BPD I, MRE Depressed, Moderate Severity
|
19 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
46 Participants
n=4 Participants
|
|
Diagnosis Disorder (Major Depressive Disorder (MDD) or Bipolar Disorder (BPD)
BPD I, MRE Depressed,Severe w/o Psychotic Features
|
46 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
74 Participants
n=4 Participants
|
|
Diagnosis Disorder (Major Depressive Disorder (MDD) or Bipolar Disorder (BPD)
BPD II, MRE Depressed
|
32 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
85 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 3-Month Through 60-Month (Post Baseline)Population: Intent-To-Treat (ITT) Population: VNS Therapy Population (n=489 (D-23=330 + D-21=159)) + (n= 276) TAU population
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.
Outcome measures
| Measure |
VNS Therapy
n=489 Participants
MADRS % Responders (Percentage of Responders)
|
Treatment As Usual (TAU)
n=276 Participants
MADRS % Responders (Percentage of Responders)
|
|---|---|---|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline)
3-Month (n=454, n=249)
|
24 Percentage of Participants
|
8.8 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline)
6-Month (n=432, n=224)
|
28 Percentage of Participants
|
13.8 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline)
9-Month (n=408, n=193)
|
33.8 Percentage of Participants
|
13.5 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline)
12-Month (n=403, n=194)
|
38.2 Percentage of Participants
|
17.5 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline)
18-Month (n=223, n=162)
|
34.1 Percentage of Participants
|
15.4 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline)
24-Month (n=233, n=146)
|
38.6 Percentage of Participants
|
18.5 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline)
30-Month (n=224, n=138)
|
34.8 Percentage of Participants
|
22.5 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline)
36-Month (n=245, n=133)
|
38.8 Percentage of Participants
|
17.3 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline)
42-Month (n=245, n=121)
|
41.2 Percentage of Participants
|
19.0 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline)
48-Month (n=246, n=109)
|
46.3 Percentage of Participants
|
22.0 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline)
54-Month (n=222, n=102)
|
48.2 Percentage of Participants
|
27.5 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline)
60-Month (n=250, n=116)
|
49.6 Percentage of Participants
|
25.9 Percentage of Participants
|
SECONDARY outcome
Timeframe: 3-Month Through 60-Month (Post Baseline)Population: Intent-To-Treat (ITT) Population: VNS Therapy Population (n=489 (D-23=330 + D-21=159)) + (n= 276) TAU population
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.
Outcome measures
| Measure |
VNS Therapy
n=151 Censored Patients
MADRS % Responders (Percentage of Responders)
|
Treatment As Usual (TAU)
n=46 Censored Patients
MADRS % Responders (Percentage of Responders)
|
|---|---|---|
|
Time Until Recurrence (TUR) for Patients That Achieved Remission, Based on Montgomery Asberg Depression Rating Scale (MADRS)
1st Quartile (25%);Time (Mo.) Until Recurrence
|
14 Months
Interval 10.0 to 19.0
|
9 Months
Interval 6.0 to 13.0
|
|
Time Until Recurrence (TUR) for Patients That Achieved Remission, Based on Montgomery Asberg Depression Rating Scale (MADRS)
Kaplan-Meier Median;Time (Mo.) Until Recurrence
|
40 Months
Interval 26.0 to
Unable to compute based on Kaplan Meier Calculation due to too few events
|
19 Months
Interval 10.0 to
Unable to compute based on Kaplan Meier Calculation due to too few events.
|
SECONDARY outcome
Timeframe: 3-Month Through 60-Month (Post Baseline)Population: Intent-To-Treat (ITT) Population: VNS Therapy Population (n=489 (D-23=330 + D-21=159)) + (n= 276) TAU population
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.
Outcome measures
| Measure |
VNS Therapy
n=489 Participants
MADRS % Responders (Percentage of Responders)
|
Treatment As Usual (TAU)
n=276 Participants
MADRS % Responders (Percentage of Responders)
|
|---|---|---|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline)
3-Month (n=454, n=249)
|
8.6 Percentage of Participants
|
2.8 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline)
6-Month (n=432, n=224)
|
15 Percentage of Participants
|
6.3 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline)
9-Month (n=408, n=193)
|
16.2 Percentage of Participants
|
5.7 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline)
12-Month (n=403, n=194)
|
19.4 Percentage of Participants
|
8.2 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline)
18-Month (n=223, n=162)
|
14.3 Percentage of Participants
|
7.4 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline)
24-Month (n=233, n=146)
|
21.9 Percentage of Participants
|
11 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline)
30-Month (n=224, n=138)
|
20.5 Percentage of Participants
|
12.3 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline)
36-Month (n=245, n=133)
|
19.2 Percentage of Participants
|
11.3 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline)
42-Month (n=245, n=121)
|
24.9 Percentage of Participants
|
13.2 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline)
48-Month (n=246, n=109)
|
25.6 Percentage of Participants
|
14.7 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline)
54-Month (n=222, n=102)
|
28.4 Percentage of Participants
|
13.7 Percentage of Participants
|
|
Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline)
60-Month (n=250, n=116)
|
27.6 Percentage of Participants
|
19 Percentage of Participants
|
SECONDARY outcome
Timeframe: 1 Week Pre-BaselinePopulation: 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.
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.
Outcome measures
| Measure |
VNS Therapy
n=763 Participants
MADRS % Responders (Percentage of Responders)
|
Treatment As Usual (TAU)
MADRS % Responders (Percentage of Responders)
|
|---|---|---|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation
0 Enjoys Life
|
6.03 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation
1
|
28.83 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation
2 Weary of Life
|
25.56 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation
3
|
18.87 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation
4 Probably Better Off Dead
|
14.81 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation
5
|
4.72 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation
6 Explicit Plans for Suicide
|
1.18 Percentage of Patients
|
—
|
SECONDARY outcome
Timeframe: BaselinePopulation: 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.
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.
Outcome measures
| Measure |
VNS Therapy
n=606 Participants
MADRS % Responders (Percentage of Responders)
|
Treatment As Usual (TAU)
MADRS % Responders (Percentage of Responders)
|
|---|---|---|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture
Patient Never Made an Attempt
|
46.70 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture
No Information or Not Sure
|
3.14 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture
No Danger
|
5.61 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture
Minimal
|
3.47 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture
Mild
|
8.91 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture
Moderate
|
18.15 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture
Severe
|
11.39 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture
Extreme
|
2.64 Percentage of Patients
|
—
|
SECONDARY outcome
Timeframe: BaselinePopulation: 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.
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.
Outcome measures
| Measure |
VNS Therapy
n=606 Participants
MADRS % Responders (Percentage of Responders)
|
Treatment As Usual (TAU)
MADRS % Responders (Percentage of Responders)
|
|---|---|---|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture
Patient Never Made an Attempt
|
46.86 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture
No Information or Not Sure
|
3.80 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture
Obviously no Intent
|
2.31 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture
Not Sure or Only Minimal Intent
|
5.12 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture
Definite But Very Ambivalent
|
11.06 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture
Serious
|
12.05 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture
Very Serious
|
9.57 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture
Extreme
|
9.24 Percentage of Patients
|
—
|
SECONDARY outcome
Timeframe: ScreeningPopulation: 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.
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.
Outcome measures
| Measure |
VNS Therapy
n=765 Participants
MADRS % Responders (Percentage of Responders)
|
Treatment As Usual (TAU)
MADRS % Responders (Percentage of Responders)
|
|---|---|---|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE
MDD, Recurrent, Moderate Severity
|
16.99 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE
MDD, Recurrent, Severe w/o Psychotic Features
|
40.39 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE
MDD, Single Episode, Moderate Severity
|
5.88 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE
MDD, Single Episode, Severe w/o Psychotic Features
|
11.24 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE
BPD I, MRE Depressed, Moderate Severity
|
5.75 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE
BPD I, MRE Depressed,Severe w/o Psychotic Features
|
9.41 Percentage of Patients
|
—
|
|
Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE
BPD II, MRE Depressed
|
10.33 Percentage of Patients
|
—
|
POST_HOC outcome
Timeframe: 3-Month (baseline or implantation) Through 60-Month (Post Baseline)Population: Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population
The number of deaths on the study were collected from the baseline visit.
Outcome measures
| Measure |
VNS Therapy
n=494 Participants
MADRS % Responders (Percentage of Responders)
|
Treatment As Usual (TAU)
n=301 Participants
MADRS % Responders (Percentage of Responders)
|
|---|---|---|
|
Mortality and Suicidality in Safety Population (Total Number of Deaths)
|
7 Number of Deaths
|
8 Number of Deaths
|
POST_HOC outcome
Timeframe: 3-Month Through 60-Month (Post Baseline)Population: Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population
Treatment exposure time in years for all patients for all treatment groups were calculated in 1000 person year measure.
Outcome measures
| Measure |
VNS Therapy
n=494 Participants
MADRS % Responders (Percentage of Responders)
|
Treatment As Usual (TAU)
n=301 Participants
MADRS % Responders (Percentage of Responders)
|
|---|---|---|
|
Mortality and Suicidality in Safety Population (Total Patient Years Exposed)
|
1985.083 Exposure Per 1000 Patient Years
|
926.493 Exposure Per 1000 Patient Years
|
POST_HOC outcome
Timeframe: 3-Month Through 60-Month (Post Baseline)Population: Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population
All cause mortality is defined as the number of deaths per calculated 1000 person years.
Outcome measures
| Measure |
VNS Therapy
n=494 Participants
MADRS % Responders (Percentage of Responders)
|
Treatment As Usual (TAU)
n=301 Participants
MADRS % Responders (Percentage of Responders)
|
|---|---|---|
|
Mortality and Suicidality in Safety Population (All-Cause Mortality/1000 Person Years)
|
3.53 Deaths Per 1000 Person Years
|
8.63 Deaths Per 1000 Person Years
|
POST_HOC outcome
Timeframe: 3-Month Through 60-Month (Post Baseline)Population: Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population
The number suicides on the study were collected from the baseline visit.
Outcome measures
| Measure |
VNS Therapy
n=494 Participants
MADRS % Responders (Percentage of Responders)
|
Treatment As Usual (TAU)
n=301 Participants
MADRS % Responders (Percentage of Responders)
|
|---|---|---|
|
Mortality and Suicidality in Safety Population (Number of Suicides)
|
2 Number of Suicides
|
2 Number of Suicides
|
POST_HOC outcome
Timeframe: 3-Month Through 60-Month (Post Baseline)Population: Safety Population (SP): VNS Therapy Population (n=494 (D-23=335 + D-21=159)) + (n= 301) TAU population
The number of suicides per calculated 1000 person years.
Outcome measures
| Measure |
VNS Therapy
n=494 Participants
MADRS % Responders (Percentage of Responders)
|
Treatment As Usual (TAU)
n=301 Participants
MADRS % Responders (Percentage of Responders)
|
|---|---|---|
|
Mortality and Suicidality in Safety Population (Suicides/1000 Person Years)
|
1.01 Number of Suicides Per 1000 Person Years
|
2.20 Number of Suicides Per 1000 Person Years
|
POST_HOC outcome
Timeframe: 3-Month Through 60-Month (Post Baseline)Population: 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.
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).
Outcome measures
| Measure |
VNS Therapy
n=330 Participants
MADRS % Responders (Percentage of Responders)
|
Treatment As Usual (TAU)
n=276 Participants
MADRS % Responders (Percentage of Responders)
|
|---|---|---|
|
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month
3 Months (n=322, n=261)
|
7.92 units on a scale
Standard Deviation 16.20
|
1.38 units on a scale
Standard Deviation 16.61
|
|
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month
6 Months (n=298, n=239)
|
9.11 units on a scale
Standard Deviation 15.66
|
4.36 units on a scale
Standard Deviation 17.46
|
|
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month
9 Months (n=270, n=216)
|
10.50 units on a scale
Standard Deviation 16.74
|
3.97 units on a scale
Standard Deviation 17.07
|
|
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month
12 Months (n=266, n=211)
|
11.04 units on a scale
Standard Deviation 18.36
|
5.49 units on a scale
Standard Deviation 17.56
|
|
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month
18 Months (n=264, n=179)
|
11.40 units on a scale
Standard Deviation 18.29
|
3.88 units on a scale
Standard Deviation 16.03
|
|
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month
24 Months (n=240, n=159)
|
13.15 units on a scale
Standard Deviation 18.13
|
7.50 units on a scale
Standard Deviation 16.73
|
|
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month
30 Months (n=223, n=147)
|
13.06 units on a scale
Standard Deviation 18.63
|
8.13 units on a scale
Standard Deviation 16.73
|
|
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month
36 Months (n=219, n=149)
|
15.59 units on a scale
Standard Deviation 18.43
|
8.34 units on a scale
Standard Deviation 16.11
|
|
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month
42 Months (n=196, n=141)
|
14.67 units on a scale
Standard Deviation 17.46
|
8.55 units on a scale
Standard Deviation 17.95
|
|
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month
48 Months (n=179, n=127)
|
14.70 units on a scale
Standard Deviation 19.02
|
9.88 units on a scale
Standard Deviation 17.28
|
|
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month
54 Months (n=156, n=128)
|
16.44 units on a scale
Standard Deviation 18.63
|
10.49 units on a scale
Standard Deviation 16.74
|
|
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Change From Baseline by Visit Month
60 Months (n=173, n=136)
|
17.20 units on a scale
Standard Deviation 17.59
|
10.11 units on a scale
Standard Deviation 17.93
|
Adverse Events
Safety Events
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Mark Bunker, PharmD, Sr. Director, Global Medical Affairs
Cyberonics, Inc
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place