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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00789854




Registration number
NCT00789854
Ethics application status
Date submitted
11/11/2008
Date registered
13/11/2008
Date last updated
23/05/2012

Titles & IDs
Public title
Comparing Quetiapine XR Monotherapy and Augmentation With Lithium Augmentation in TRD Patients
Scientific title
A Randomised, 6-week, Multicentre, Open-label, Rater-blinded Parallel Group Study Comparing Quetiapine Extended Release Monotherapy and Augmentation With Lithium Augmentation in Patients With Treatment Resistant Depression
Secondary ID [1] 0 0
D1443L00044
Universal Trial Number (UTN)
Trial acronym
RUBY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder 0 0
Treatment Resistant Depression 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Quetiapine XR
Treatment: Drugs - Lithium carbonate
Treatment: Drugs - SSRI/Venlafaxine

Active Comparator: Add-on Quetiapine XR+SSRI/Venlafaxine - Selective serotonin reuptake inhibitors (SSRI) or Venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od).
From previous anti-depressant treatment 64% of the patients had SSRI and 35% had Venlafaxine at baseline.

Active Comparator: Add-on Lithium+SSRI/Venlafaxine - Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od).
From previous anti-depressant treatment 67% of the patients had SSRI and 33% had Venlafaxine at baseline.

Active Comparator: Monotherapy Quetiapine XR - Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)


Treatment: Drugs: Quetiapine XR
300 mg once daily (od)

Treatment: Drugs: Lithium carbonate
900 mg once daily (od)

Treatment: Drugs: SSRI/Venlafaxine
SSRI - doses within label, Venlafaxine dose up to 225 mg/day

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in Depressive Symptoms Between Randomisation and Week 6 Measured by Change in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Per Protocol Analysis Set) - Change in LS mean total Montgomery Asberg Depression Rating Scale (MADRS) score from randomisation to end-of-treatment (week 6) (Scale 0-60), lower score indicates a better health status.
Timepoint [1] 0 0
6 weeks treatment
Primary outcome [2] 0 0
Change in Depressive Symptoms Between Randomisation and Week 6 Measured by Change in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Modified Intention to Treat Analysis Set) - Change in LS mean total Montgomery Asberg Depression Rating Scale (MADRS) score from randomisation to end-of-treatment (week 6) (Scale 0-60), lower score indicates a better health status.
Timepoint [2] 0 0
6 weeks of treatment
Secondary outcome [1] 0 0
Depression Remission; Montgomery-Asberg Depression Rating Scale MADRS =10, All Patients - Number of patients in remission, with total Montgomery Asberg Depression Rating Scale (MADRS) score =10. MADRS scale has range from 0 to 60, where the lower score indicates the better health status.
Timepoint [1] 0 0
6 weeks of treatment
Secondary outcome [2] 0 0
Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) =10, Patients With One Previous Treatment Failure - Number of patients in remission with one previous treatment failure and with total Montgomery Asberg Depression Rating Scale (MADRS) score =10. MADRS scale has range from 0 to 60, where the lower score indicates the better health status.
Timepoint [2] 0 0
6 weeks of treatment
Secondary outcome [3] 0 0
Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) =10, Patients With Two Previous Treatment Failure - Number of patients in remission with two previous treatment failure and with total Montgomery Asberg Depression Rating Scale (MADRS) score =10. MADRS scale has range from 0 to 60, where the lower score indicates the better health status.
Timepoint [3] 0 0
6 weeks of treatment
Secondary outcome [4] 0 0
Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) =8 - Number of patients in remission with total Montgomery Asberg Depression Rating Scale (MADRS) score =8. MADRS scale has range from 0 to 60, where the lower score indicates the better health status.
Timepoint [4] 0 0
6 weeks of treatment
Secondary outcome [5] 0 0
Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) =12 - Number of patients in remission with total Montgomery Asberg Depression Rating Scale (MADRS) score =12. MADRS scale has range from 0 to 60, where the lower score indicates the better health status.
Timepoint [5] 0 0
6 weeks of treatment
Secondary outcome [6] 0 0
Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced = 50%, All Patients - Response rate at end of study measured as number of patients with Montgomery Asberg Depression Rating Scale (MADRS) with total score reduction = 50% compared to baseline, the higher number of patients the better
Timepoint [6] 0 0
6 week of treatments
Secondary outcome [7] 0 0
Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced = 50%, Patients With One Previous Treatment Failure - Response rate at end of study measured as number of patients with Montgomery Asberg Depression Rating Scale (MADRS) with total score reduction = 50% compared to baseline, the higher number of patients the better
Timepoint [7] 0 0
6 weeks of treatment
Secondary outcome [8] 0 0
Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced = 50%, Patients With Two Previous Treatment Failure - Response rate at end of study measured as number of patients with Montgomery Asberg Depression Rating Scale (MADRS) with total score reduction = 50% compared to baseline, the higher number of patients the better
Timepoint [8] 0 0
6 weeks of treatment
Secondary outcome [9] 0 0
Responder: Clinical Global Impression Improvement (CGI-I) Item 2, All Patients - Change in global improvement measured by Clinical Global Impression Improvement (CGI-I). Scale from 1-4, where lower value shows a larger improvement.
Timepoint [9] 0 0
6 weeks of treatment
Secondary outcome [10] 0 0
Responder: Clinical Global Impression Improvement (CGI)-I Item 2, Patients With One Previous Treatment Failure - Change in global improvement measured by Clinical Global Impression Improvement (CGI-I). Scale from 1-4, where a lower value shows a larger improvement.
Timepoint [10] 0 0
6 weeks of treatment
Secondary outcome [11] 0 0
Responder: Clinical Global Impression Improvement (CGI-I) Item 2, Patients With Two Previous Treatment Failure - Change in global improvement measured by Clinical Global Impression Improvement (CGI-I). Scale from 1-4, where a lower value shows a larger improvement.
Timepoint [11] 0 0
6 weeks of treatment
Secondary outcome [12] 0 0
Change in Clinical Global Impression Scale (CGI-S), All Patients - Change in severity of illness measured by Clinical Global Impression Scale (CGI-S). Scale form 1-7, where a lower value shows a larger improvement.
Timepoint [12] 0 0
6 weeks of treatment
Secondary outcome [13] 0 0
Change in Clinical Global Impression Scale (CGI-S), Patients With One Previous Treatment Failure - Change in severity of illness measured by Clinical Global Impression Scale (CGI-S). Scale from 1-7, where a lower value shows a larger improvement.
Timepoint [13] 0 0
6 weeks of treatment
Secondary outcome [14] 0 0
Change in Clinical Global Impression Scale (CGI-S), Patients With Two Previous Treatment Failure - Change in severity of illness measured by Clinical Global Impression Scale (CGI-S). Scale from 1-7, where a lower value shows a larger improvement.
Timepoint [14] 0 0
6 weeks of treatment
Secondary outcome [15] 0 0
Change in Beck Depression Inventory (BDI) - Self-rating assessment of depressive symptoms using Beck Depression Inventory (BDI). Scale from 0-63, where a lower value shows a larger improvement.
Timepoint [15] 0 0
6 weeks of treatment
Secondary outcome [16] 0 0
Change in Pain, Measured by Visual Analog Scale (VAS) - Self-rating assessment of pain using a visual analogue scale (VAS). Scale from 0-100, where a lower value shows a larger improvement.
Timepoint [16] 0 0
6 weeks of treatment
Secondary outcome [17] 0 0
Change in Anxiety Measured by Visual Analog Scale (VAS) - Self-rating assessment of anxiety using a visual analogue scale (VAS). Scale from 0-100, where a lower value shows a larger improvement.
Timepoint [17] 0 0
6 weeks of treatment
Secondary outcome [18] 0 0
Change in Anxiety Measured by State-Trait Anxiety Inventory (STAI), State Anxiety Inventory - Self-rating assessment of anxiety measured by STAI, state anxiety inventory (Scale 20-80, where a lower value shows a larger improvement)
Timepoint [18] 0 0
6 weeks of treatment
Secondary outcome [19] 0 0
Change in Anxiety Measured by STAI, Trait Anxiety Inventory - Self-rating assessment of anxiety measured by State-Trait Anxiety Inventory (STAI), trait anxiety inventory (Scale 20-80, where a lower value shows a larger improvement)
Timepoint [19] 0 0
6 weeks of treatment
Secondary outcome [20] 0 0
Change in Sleep Quality Measured by Montgomery Asberg Depression Rating Scale (MADRS), Item 4 - Sleeping quality measured by Montgomery-Asberg Depression Rating Scale (MADRS) item 4 (reduced sleep) (Scale 0-6, where a lower value shows a larger improvement)
Timepoint [20] 0 0
6 weeks of treatment
Secondary outcome [21] 0 0
Change in Sleep Quality Measured by Pittsburgh Sleep Quality Index (PSQI) - Self-rated sleeping quality measured by PSQI (Scale 0-21, subscales 0-3, 18 questions, where a lower value shows a larger improvement)
Timepoint [21] 0 0
6 weeks of treatment
Secondary outcome [22] 0 0
Change in Quality of Life Measured by Short-form Health Survey (SF-36), Mental Component - Self rating assessment of quality in life using SF-36, mental component (Scale 0-100, where a higher value shows a larger improvement)
Timepoint [22] 0 0
6 weeks of treatment
Secondary outcome [23] 0 0
Change in Quality of Life Measured by Short-form Health Survey (SF-36), Physical Component - Self rating assessment of quality in life using SF-36, physical component (Scale 0-100, where a higher value shows a larger improvement)
Timepoint [23] 0 0
6 weeks of treatment
Secondary outcome [24] 0 0
Change in Quality of Life Measured by Health Questionnaire EQ-5D as Utility - Self rating assessment of quality in life using EQ-5D utility (Scale 0-100, where a higher value shows a larger improvement)
Timepoint [24] 0 0
6 weeks of treatment
Secondary outcome [25] 0 0
Change in Work Productivity and Activity Impairment: General Health (WPAI:GH) - Self rating assessment of working productivity using WPAI:GH (Scale 0 to number of hours worked during a week multiplied with the salary in Euro, a lower value shows a larger improvement)
Timepoint [25] 0 0
6 weeks of treatment
Secondary outcome [26] 0 0
Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, All Patients - The physician has evaluated the therapeutic effect and the side effect combined at end of study. Patients with a 'marked/moderate' therapeutic effect and 'None/Do Not Significantly Interfere' side effect has been added. The higher values show more patients with a treatment effect without any side-effect. The range is from 0 patients to the maximum number of patients in the treatment arm (225, 229 or 221).
Timepoint [26] 0 0
6 weeks of treatment
Secondary outcome [27] 0 0
Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With One Previous Treatment Failure - The physician has evaluated the therapeutic effect and the side effect combined at end of study. Patients with a 'marked/moderate' therapeutic effect and 'None/Do Not Significantly Interfere' side effect has been added. The higher values show more patients with a treatment effect without any side-effect. The range is from 0 patients to the maximum number of patients in the treatment arm.
Timepoint [27] 0 0
6 weeks of treatment
Secondary outcome [28] 0 0
Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With Two Previous Treatment Failures - The physician has evaluated the therapeutic effect and the side effect combined at end of study. Patients with a 'marked/moderate' therapeutic effect and 'None/Do Not Significantly Interfere' side effect has been added. The higher values show more patients with a treatment effect without any side-effect. The range is from 0 patients to the maximum number of patients in the treatment arm.
Timepoint [28] 0 0
6 week of treatments

Eligibility
Key inclusion criteria
- Documented clinical diagnosis as confirmed by the M.I.N.I. meeting criteria from the
Diagnostic and Statistical Manual of Mental disorders, 4th Edition (DSM-IV) for any of
the following:296.2x MDD, Single Episode296.3x MDD, Recurrent Episode

- Current episode of depression present, at least 42 days prior to enrolment but not
more than 18 months

- MADRS-Score = 25 at enrolment and randomisation
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with a DSM-IV Axis I disorder other than MDD within 6 months of randomisation

- Patients with a diagnosis of DSM-IV Axis II disorder which has a major impact on the
patient's current psychiatric status

- Patients who, in the investigator's judgment pose a current serious suicidal or
homicidal risk, or have made a suicide attempt within the past 6 months

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,QLD,SA,VIC
Recruitment hospital [1] 0 0
Research Site - Garran
Recruitment hospital [2] 0 0
Research Site - Brisbane
Recruitment hospital [3] 0 0
Research Site - Everton Park
Recruitment hospital [4] 0 0
Research Site - Townsville
Recruitment hospital [5] 0 0
Research Site - Gilberton
Recruitment hospital [6] 0 0
Research Site - Clayton
Recruitment hospital [7] 0 0
Research Site - Frankston
Recruitment hospital [8] 0 0
Research Site - Heidelberg
Recruitment hospital [9] 0 0
Research Site - Malvern
Recruitment hospital [10] 0 0
Research Site - Prahran
Recruitment hospital [11] 0 0
Research Site - Richmond
Recruitment postcode(s) [1] 0 0
- Garran
Recruitment postcode(s) [2] 0 0
- Brisbane
Recruitment postcode(s) [3] 0 0
- Everton Park
Recruitment postcode(s) [4] 0 0
- Townsville
Recruitment postcode(s) [5] 0 0
- Gilberton
Recruitment postcode(s) [6] 0 0
- Clayton
Recruitment postcode(s) [7] 0 0
- Frankston
Recruitment postcode(s) [8] 0 0
- Heidelberg
Recruitment postcode(s) [9] 0 0
- Malvern
Recruitment postcode(s) [10] 0 0
- Prahran
Recruitment postcode(s) [11] 0 0
- Richmond
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Graz
Country [2] 0 0
Austria
State/province [2] 0 0
Klagenfurt
Country [3] 0 0
Austria
State/province [3] 0 0
Salzburg
Country [4] 0 0
Austria
State/province [4] 0 0
Wels
Country [5] 0 0
Austria
State/province [5] 0 0
Wiener NEUSTADT
Country [6] 0 0
Austria
State/province [6] 0 0
Wien
Country [7] 0 0
Belgium
State/province [7] 0 0
Assebroek
Country [8] 0 0
Belgium
State/province [8] 0 0
Diest
Country [9] 0 0
Belgium
State/province [9] 0 0
Liege
Country [10] 0 0
Belgium
State/province [10] 0 0
Tielt
Country [11] 0 0
Bulgaria
State/province [11] 0 0
Veliko Tarnovo
Country [12] 0 0
Bulgaria
State/province [12] 0 0
Kardjali
Country [13] 0 0
Bulgaria
State/province [13] 0 0
Pazardjik
Country [14] 0 0
Bulgaria
State/province [14] 0 0
Pleven
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Ruse
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Sofia
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Varna
Country [18] 0 0
Denmark
State/province [18] 0 0
Esbjerg N
Country [19] 0 0
Denmark
State/province [19] 0 0
Frederiksberg
Country [20] 0 0
Denmark
State/province [20] 0 0
Odense
Country [21] 0 0
Germany
State/province [21] 0 0
Aachen
Country [22] 0 0
Germany
State/province [22] 0 0
Achim
Country [23] 0 0
Germany
State/province [23] 0 0
Augsburg
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Germany
State/province [24] 0 0
Bad Homburg
Country [25] 0 0
Germany
State/province [25] 0 0
Bad Honnef
Country [26] 0 0
Germany
State/province [26] 0 0
Bad Saarow
Country [27] 0 0
Germany
State/province [27] 0 0
Berlin
Country [28] 0 0
Germany
State/province [28] 0 0
Bielefeld
Country [29] 0 0
Germany
State/province [29] 0 0
Bochum
Country [30] 0 0
Germany
State/province [30] 0 0
Butzbach
Country [31] 0 0
Germany
State/province [31] 0 0
Chemnitz
Country [32] 0 0
Germany
State/province [32] 0 0
Dresden
Country [33] 0 0
Germany
State/province [33] 0 0
Duren
Country [34] 0 0
Germany
State/province [34] 0 0
Dusseldorf
Country [35] 0 0
Germany
State/province [35] 0 0
Ellwangen
Country [36] 0 0
Germany
State/province [36] 0 0
Erbach
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Germany
State/province [37] 0 0
Gelsenkirchen
Country [38] 0 0
Germany
State/province [38] 0 0
Gutersloh
Country [39] 0 0
Germany
State/province [39] 0 0
Halle
Country [40] 0 0
Germany
State/province [40] 0 0
Hattingen
Country [41] 0 0
Germany
State/province [41] 0 0
Herborn
Country [42] 0 0
Germany
State/province [42] 0 0
Kassel
Country [43] 0 0
Germany
State/province [43] 0 0
Kothen
Country [44] 0 0
Germany
State/province [44] 0 0
Neu-isenburg
Country [45] 0 0
Germany
State/province [45] 0 0
Neubrandenburg
Country [46] 0 0
Germany
State/province [46] 0 0
Nurnberg
Country [47] 0 0
Germany
State/province [47] 0 0
Oldenburg
Country [48] 0 0
Germany
State/province [48] 0 0
Ostfildern
Country [49] 0 0
Germany
State/province [49] 0 0
Schwerin
Country [50] 0 0
Germany
State/province [50] 0 0
Stuttgart
Country [51] 0 0
Germany
State/province [51] 0 0
Westerstede
Country [52] 0 0
Germany
State/province [52] 0 0
Wurzburg
Country [53] 0 0
Hungary
State/province [53] 0 0
Budapest
Country [54] 0 0
Hungary
State/province [54] 0 0
Gyor
Country [55] 0 0
Hungary
State/province [55] 0 0
Gyula
Country [56] 0 0
Hungary
State/province [56] 0 0
Nyiregyhaza
Country [57] 0 0
Italy
State/province [57] 0 0
BZ
Country [58] 0 0
Italy
State/province [58] 0 0
CA
Country [59] 0 0
Italy
State/province [59] 0 0
PI
Country [60] 0 0
Italy
State/province [60] 0 0
RM
Country [61] 0 0
Italy
State/province [61] 0 0
Bolzano
Country [62] 0 0
Italy
State/province [62] 0 0
Catania
Country [63] 0 0
Italy
State/province [63] 0 0
Napoli
Country [64] 0 0
Italy
State/province [64] 0 0
Roma
Country [65] 0 0
Portugal
State/province [65] 0 0
Braga
Country [66] 0 0
Portugal
State/province [66] 0 0
Coimbra
Country [67] 0 0
Portugal
State/province [67] 0 0
Lisboa
Country [68] 0 0
Portugal
State/province [68] 0 0
Santarem
Country [69] 0 0
Romania
State/province [69] 0 0
Bucharest
Country [70] 0 0
Romania
State/province [70] 0 0
Craiova
Country [71] 0 0
Romania
State/province [71] 0 0
Galati
Country [72] 0 0
Romania
State/province [72] 0 0
Sibiu
Country [73] 0 0
Slovakia
State/province [73] 0 0
Bratislava
Country [74] 0 0
Slovakia
State/province [74] 0 0
Krupina
Country [75] 0 0
Slovakia
State/province [75] 0 0
Levice
Country [76] 0 0
Slovakia
State/province [76] 0 0
Liptovsky Mikulas
Country [77] 0 0
Slovakia
State/province [77] 0 0
Michalovce Stranany
Country [78] 0 0
Slovakia
State/province [78] 0 0
Presov
Country [79] 0 0
Slovakia
State/province [79] 0 0
Roznava
Country [80] 0 0
Slovakia
State/province [80] 0 0
Zilina-bytcica
Country [81] 0 0
Slovakia
State/province [81] 0 0
Zlate Moravce
Country [82] 0 0
Spain
State/province [82] 0 0
Asturias
Country [83] 0 0
Spain
State/province [83] 0 0
Castilla Leon
Country [84] 0 0
Spain
State/province [84] 0 0
Cataluna
Country [85] 0 0
Spain
State/province [85] 0 0
Galicia
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Surrey
Country [87] 0 0
United Kingdom
State/province [87] 0 0
Warrington
Country [88] 0 0
United Kingdom
State/province [88] 0 0
West Sussex
Country [89] 0 0
United Kingdom
State/province [89] 0 0
Coventry
Country [90] 0 0
United Kingdom
State/province [90] 0 0
Glasgow
Country [91] 0 0
United Kingdom
State/province [91] 0 0
Harrow
Country [92] 0 0
United Kingdom
State/province [92] 0 0
Hull
Country [93] 0 0
United Kingdom
State/province [93] 0 0
Winsford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of the study is to evaluate the efficacy of Quetiapine extended release
(XR) in combination with an selective serotonin reuptake inhibitor (SSRI) or Venlafaxine
versus Lithium in combination with an selective serotonin reuptake inhibitor or Venlafaxine
versus Quetiapine extended release monotherapy in subjects with treatment resistant
depression as assessed by the changes from randomisation to week 6 in the Montgomery-Åsberg
Depression Rating Scale (MADRS) total score. As an independent objective, the primary
objective will also be evaluated in two subgroups of patients: (1) patients who were
resistant to two previous antidepressant therapies and (2) in the subgroup of patients with
one previous failure.
Trial website
https://clinicaltrials.gov/show/NCT00789854
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael Bauer, professor
Address 0 0
Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications