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Trial registered on ANZCTR


Registration number
ACTRN12613000256774
Ethics application status
Approved
Date submitted
1/03/2013
Date registered
5/03/2013
Date last updated
5/03/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Escitalopram efficacy and tolerability in treatment resistant depression. an open study.
Scientific title
The objective of this European multicentre study was to evaluate escitalopram efficacy and tolerability in a population which has been shown to have Treatment Resistant Depression (TRD) in a prospective open treatment phase with venlafaxine over a 6 week period at an adequate dose after non response to previous antidepressants
Secondary ID [1] 282048 0
nil
Universal Trial Number (UTN)
Nil
Trial acronym
TRDII
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depression 288521 0
Condition category
Condition code
Mental Health 288853 288853 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients meeting the entry criteria and for whom the investigator considered switching to venlafaxine, were included in a 6 week prospective treatment with venlafaxine (AD2) prescribed continuously at its optimal dose.
Initial venlafaxine oral tablets daily dose was 75 mg; the daily dose could be further increased to 150 mg after 1 week, on the basis of an unsatisfactory response as judged by the investigator. If necessary, the dose could be increased up to a maximum of 225 mg.

Escitalopram Treatment
Patients considered as non responders at the end of the venlafaxine treatment were evaluated for inclusion in the second phase of the trial. To be eligible for inclusion in the 6-week prospective treatment with escitalopram (AD3) each patient had to meet 1 of the 2 following inclusion criteria:
1. At day 28: the patient has a total score =20 on the MADRS and a decrease from start of the venlafaxine treatment in Montgomery–Asberg Depression Rating Scale (MADRS) total score <25%;
2. At day 42: patient has a total score equal or more than 20 on the MADRS or a decrease from start of the venlafaxine treatment in MADRS total score <50%.
Exclusion Criteria: any patient who met the following criteria at the end of the venlafaxine treatment was not included in the escitalopram treatment: 1. The patient had not taken AD2 medication for three consecutive days or more, or overall compliance was less than 80% during the venlafaxine treatment; 2. any of the previously described exclusion criteria that appeared since the initiation of the venlafaxine treatment.

Initial escitalopram oral tablets daily dose was 10 mg; the daily dose had to be increased to 20 mg after 1 week; after 2 weeks, the daily dose could be further increased to 30 mg on the basis of an unsatisfactory response as judged by the investigator.
Intervention code [1] 286639 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 288982 0
To evaluate the efficacy of escitalopram in TRD, assessed by 2 consecutive failed antidepressant treatments, the last treatment received being a 6 week prospective trial with venlafaxine. The considered primary outcome was the Montgomery–Asberg Depression Rating Scale (MADRS) score.
Timepoint [1] 288982 0
6 weeks after venlafaxine
Secondary outcome [1] 301497 0
To evaluate efficacy of escitalopram considering the Hamilton Rating Scale for Depression (HRSD)
Timepoint [1] 301497 0
6 weeks
Secondary outcome [2] 301516 0
evaluation of psychic and somatic side effects by Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU)
Timepoint [2] 301516 0
Day 0, 14, 28, 42, 56, 70, 84
Secondary outcome [3] 301563 0
To evaluate efficacy of escitalopram considering the Clinical Global Impression Severity (CGI-S)
Timepoint [3] 301563 0
6 weeks
Secondary outcome [4] 301564 0
To evaluate efficacy of escitalopram considering the Clinical Global Impression Improvement (CGI-I)
Timepoint [4] 301564 0
6 weeks

Eligibility
Key inclusion criteria
To be included in the 6 week prospective treatment with venlafaxine each patient had to: 1. be able to read and understand the patient information sheet; 2. have signed the informed consent form; 3. be an in- or outpatient, male or female, of at least 18 years of age; 4. have a Current Major Depressive Episode, assessed with the Mini International Neuropsychiatric Interview (MINI), moderate or severe, according to DSM-IV-TR criteria (classification codes: 296.2x or 296.3x); 5. have been treated for the Current Episode with any antidepressant (AD1) (other than escitalopram or venlafaxine) prescribed continuously at its optimal dose (Annex 1) for at least 4 weeks (criterion verified at screening) – if at inclusion the patient was not during AD1 period of any antidepressant, this period without antidepressant should not have exceeded 4 weeks); 6. be a non-responder to this previous treatment (AD1) (Montgomery Asberg Depression Rating Scale (MADRS) improvement <50%); 7. have a total score equal or above 22 on the MADRS.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
To be excluded from the study each patient had to: 1. have previously participated in this study; 2. be a non responder to a combination of 2 antidepressants (at least 2 weeks of treatment with an adequate dose for each of the 2 drugs) and/or to an augmentation therapy (at least 2 weeks with a potentiating agent at any dose) at the time of screening; 3. have a history of severe drug allergy or hypersensitivity, or known hypersensitivity to escitalopram or venlafaxine; 4. have one or more of the following conditions: a. any Current Psychiatric Disorder established as the principal diagnosis other than Major Depressive Disorder as defined in the DSM-IV-TR (assessed with the MINI); b. any Substance Disorder (except nicotine and caffeine) within the previous 6 months as defined in the DSM-IV-TR; c. any severe Personality Disorder according to investigator clinical judgement that might compromise the study; 5. have received one or more of the following disallowed treatments: a. oral antipsychotic drugs had to have been stopped at least 2 weeks before inclusion; the patient could be included if the antipsychotic medication had been taken at infra-therapeutic dose (lower than the recommended dose as indicated in the notice of the product); patients were excluded if they had received a depot antipsychotic preparation within the past 6 months; b. ECT within the past 6 months; c. lithium, carbamazepine, lamotrigine, valproate or valpromide at therapeutic dose and for more than 2 weeks within the past month; d. benzodiazepines: more than 25 mg/day of diazepam or equivalent within the last week for chronic users of benzodiazepines (more than 3 months on treatment) and more than 10 mg/day of diazepam or equivalent for non chronic users (less than 3 months); e. more than 20 mg/day of zolpidem, 15 mg/day of zopiclone or 20 mg/day of zaleplon within the last week; f. any non-benzodiazepine anxiolytic within the last week; g. any serotonin agonist (e.g., triptans) within the last week; h. any other drug with potential psychotropic effects within the last week; i. any investigational product within 3 months prior to screening; j. escitalopram or venlafaxine at adequate dose and duration during the Current Episode; k. formal psychotherapy started in the month preceding inclusion; 6. have a previous history of convulsive disorder other than a single childhood febrile seizure; 7. present evidence of urinary retention or glaucoma; 8. have a serious illness and/or serious sequelae thereof, including liver or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, infectious, neoplastic, or metabolic disturbance; 9. have, in the opinion of the investigator (based on physical examination, medical history and vital signs), comorbid conditions(s) that would render inclusion in the study unsafe; 10. take medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy; 11. in female patients, be pregnant or breastfeed at inclusion as well as during the study; 12. be, in the opinion of the investigator, unlikely to comply with the clinical study protocol or is unsuitable for any reason.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients meeting the above criteria and for whom the investigator considered switching to venlafaxine, were included in a 6 week prospective treatment with venlafaxine (AD2) prescribed continuously at its optimal dose.
Initial venlafaxine daily dose was 75 mg; the daily dose could be further increased to 150 mg after 1 week, on the basis of an unsatisfactory response as judged by the investigator. If necessary, the dose could be increased up to a maximum of 225 mg.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
none
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
sequential
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The primary analysis was a repeated-measure ANOVA analysis of variance focused on Day 14, 28, 42, 56, 70 and 84 MADRS change from baseline (Day 0). Focus was on Intent To Treat (ITT) patients, but analyses on completers were also performed.
The secondary analyses of HRSD, CGI-S and CGI-I change scores from baseline were carried out in line with the primary analysis.
P-value was set at 0.05 level. The sample had sufficient power (0.80) to detect a small effect size (f equal to 0.07) that, as an example, corresponds to a final difference in the total MADRS score of 0.59 points.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/01/2005
Actual
1/01/2005
Date of last participant enrolment
Anticipated
31/12/2011
Actual
31/12/2011
Date of last data collection
Anticipated
Actual
Sample size
Target
417
Accrual to date
Final
Recruitment outside Australia
Country [1] 4888 0
Belgium
State/province [1] 4888 0
Country [2] 4889 0
Austria
State/province [2] 4889 0
Country [3] 4890 0
Italy
State/province [3] 4890 0
Country [4] 4891 0
Israel
State/province [4] 4891 0
Country [5] 4892 0
France
State/province [5] 4892 0
Country [6] 4893 0
Greece
State/province [6] 4893 0

Funding & Sponsors
Funding source category [1] 286821 0
Commercial sector/Industry
Name [1] 286821 0
Lundbeck
Country [1] 286821 0
Denmark
Primary sponsor type
Commercial sector/Industry
Name
Lundbeck
Address
Ottiliavej 9, 2500 Valby, Copenhagen
Country
Denmark
Secondary sponsor category [1] 285609 0
None
Name [1] 285609 0
Address [1] 285609 0
Country [1] 285609 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288887 0
ULB
Ethics committee address [1] 288887 0
Ethics committee country [1] 288887 0
Belgium
Date submitted for ethics approval [1] 288887 0
Approval date [1] 288887 0
07/09/2004
Ethics approval number [1] 288887 0
P2004/104

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 38234 0
Dr Daniel Souery
Address 38234 0
Psy Pluriel, Centre Europeen de Psychologie Medicale
47 Av Jacques Pastur
1180 Bruxelles
Country 38234 0
Belgium
Phone 38234 0
+32 2 3315665
Fax 38234 0
+32 2 3315666
Email 38234 0
[email protected]
Contact person for public queries
Name 38235 0
Daniel Souery
Address 38235 0
Psy Pluriel, Centre Europeen de Psychologie Medicale
47 Av Jacques Pastur
1180 Bruxelles
Country 38235 0
Belgium
Phone 38235 0
+32 2 3315665
Fax 38235 0
+32 2 3315666
Email 38235 0
[email protected]
Contact person for scientific queries
Name 38236 0
Daniel Souery
Address 38236 0
Psy Pluriel, Centre Europeen de Psychologie Medicale
47 Av Jacques Pastur
1180 Bruxelles
Country 38236 0
Belgium
Phone 38236 0
+32 2 3315665
Fax 38236 0
+32 2 3315666
Email 38236 0
[email protected]

No information has been provided regarding IPD availability


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Results publications and other study-related documents

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