Major Depressive DisorderPhase 3REVIVENCT01488071
A Study of Vortioxetine (Lu AA21004) in Comparison to Agomelatine in Adults Suffering From Major Depression With Inadequate Response to Previous Medication
A Phase 3 study testing Vortioxetine (Lu AA21004) and Agomelatine in people with Major Depressive Disorder, run by H. Lundbeck A/S.
Trial summary
The objective of the present study is to evaluate whether vortioxetine (10 or 20 mg/day) is at least as effective as agomelatine (25 to 50 mg/day) in patients with depressive symptoms that showed inadequate response to Serotonin Reuptake Inhibitors (SRI) antidepressants. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Vortioxetine (Lu AA21004) and Agomelatine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 495 participants
- Where
- No sites listed yet
- Study dates
- Jan 2012to Dec 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient is being treated with a serotonin reuptake inhibitor (SRI) antidepressant (monotherapy) that was prescribed to treat Major Depressive Episode (DSM-IV-TR criteria)
- The response to the current SRI treatment is inadequate and patient agrees to discontinue the current SRI at the baseline
- Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥22 at the Screening Visit and Baseline
- The patient, if a woman, must: agree not to try to become pregnant during the study, AND use adequate, highly effective contraception
Who cannot join
- The patient has any current Axis I disorders (DSM-IV criteria) other than Major Depressive Disorder (MDD), General Anxiety Disorder (GAD) and Social Anxiety Disorder (SAD)
- The patient is at significant risk of suicide
- The patient is currently receiving formal psychotherapy or other psychoactive medications
- Other protocol-defined inclusion and exclusion criteria may apply.
About this study
Official title: A Randomised, Double-blind, Parallel-group, Active-controlled, Flexible Dose Study Evaluating the Effects of [Vortioxetine] Lu AA21004 Versus Agomelatine in Adult Patients Suffering From Major Depressive Disorder With Inadequate Response to Antidepressant Treatment
The objective of the present study is to evaluate whether vortioxetine (10 or 20 mg/day) is at least as effective as agomelatine (25 to 50 mg/day) in patients with depressive symptoms that showed inadequate response to Serotonin Reuptake Inhibitors (SRI) antidepressants.
- Conditions
- Major Depressive Disorder
- Being tested
- Vortioxetine (Lu AA21004), Agomelatine
- Keywords
- Depression, Multimodal antidepressant
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vortioxetine (Lu AA21004)Drug
Also called Brintellix®
encapsulated tablets, daily, orally
AgomelatineDrug
Also called Valdoxan®
encapsulated tablets, daily, orally
| Study group | Role | What they receive |
|---|---|---|
| Vortioxetine 10 mg or 20 mg | Experimental | Not described Receives: Drug: Vortioxetine (Lu AA21004) |
| Agomelatine 25 mg or 50 mg | Active comparator | Not described Receives: Drug: Agomelatine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in MADRS Total Score at Week 8
The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 (no symptom) to 6 (severe symptom). The 10 items represent the core symptoms of depressive illness. The rating should be based on a clinical interview with the patient, moving from broadly phrased questions about symptoms to more detailed ones, which allow a precise rating of severity, covering the last 7 days. Total score from 0 to 60. The higher the score, the more severe, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
Measured: Baseline and Week 8
Secondary outcomes (13)
Change From Baseline in MADRS Total Score at Week 12
Measured: Baseline and Week 12
Change From Baseline in HAM-A Total Score at Week 8
The Hamilton Anxiety Rating Scale (HAM-A) consists of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behaviour at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic, and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total score from 0 to 56; higher score indicates greater anxiety, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
Measured: Baseline and Week 8
Change From Baseline in HAM-A Total Score at Week 12
Measured: Baseline and Week 12
Change From Baseline in CGI-S Score at Week 8
The Clinical Global Impression - Severity of Illness (CGI-S) is a 7-point scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The investigator should use his/her total clinical experience with this patient population to judge how mentally ill the patient is at the time of rating. Higher score indicates that the subject is more ill, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
Measured: Baseline and Week 8
Change From Baseline in CGI-S Score at Week 12
Measured: Baseline and Week 12
Change in Clinical Status Using CGI-I Score at Week 8
The Clinical Global Impression - Global Improvement (CGI-I) is a 7-point scale rated from 1 (very much improved) to 7 (very much worse). The investigator rated the patient's overall improvement relative to baseline, whether or not, in the opinion of the investigator, this was entirely due to the drug treatment. Higher score = more affected.
Measured: Week 8
Change in Clinical Status Using CGI-I Score at Week 12
Measured: Week 12
Proportion of Patients Who Respond at Week 8 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)
Measured: Baseline and Week 8
Proportion of Patients Who Respond at Week 12 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)
Measured: Baseline and Week 12
Proportion of Patients Who Are in Remission at Week 8 (Remission is Defined as a MADRS Total Score <=10)
Measured: Week 8
Proportion of Patients Who Are in Remission at Week 12 (Remission is Defined as a MADRS Total Score <=10)
Measured: Week 12
Change From Baseline in SDS Total Score at Week 8
The Sheehan Disability Scale (SDS) comprises self-rated items designed to measure impairment. The patient rates the extent to which his or her (1) work, (2) social life or leisure activities and (3) home life or family responsibilities are impaired on a 10-point visual analogue scales, on which 0 = normal functioning and 10 = severe functional impairment. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired). The higher the score, the more severe, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
Measured: Baseline and Week 8
Change From Baseline in SDS Total Score at Week 12
Measured: Baseline and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2011 (estimated)
- Study startJan 2012
- Primary completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by H. Lundbeck A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 495 participants (actual)
Sponsor and investigators
- Lead sponsor
- H. Lundbeck A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Email contact via H. Lundbeck A/S, Study director, LundbeckClinicalTrials@lundbeck.com
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01488071
- Sponsor's protocol ID
- 14178A
- Other IDs
- 2011-002362-21
- Acronym
- REVIVE
- Status last verified
- Feb 2014
- First submitted
- 29 Nov 2011
- Last updated
- 26 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Adair M, Christensen MC, Florea I, Loft H, Fagiolini A. Vortioxetine in patients with major depressive disorder and high levels of anxiety symptoms: An updated analysis of efficacy and tolerability. J Affect Disord. 2023 May 1;328:345-354. doi: 10.1016/j.jad.2023.01.074. Epub 2023 Jan 26.
PubMed 36708956Papakostas GI, Nielsen RZ, Dragheim M, Tonnoir B. Efficacy and tolerability of vortioxetine versus agomelatine, categorized by previous treatment, in patients with major depressive disorder switched after an inadequate response. J Psychiatr Res. 2018 Jun;101:72-79. doi: 10.1016/j.jpsychires.2018.02.017. Epub 2018 Feb 22.
PubMed 29554497Montgomery SA, Nielsen RZ, Poulsen LH, Haggstrom L. A randomised, double-blind study in adults with major depressive disorder with an inadequate response to a single course of selective serotonin reuptake inhibitor or serotonin-noradrenaline reuptake inhibitor treatment switched to vortioxetine or agomelatine. Hum Psychopharmacol. 2014 Sep;29(5):470-82. doi: 10.1002/hup.2424.
PubMed 25087600
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Parallel-group, Active-controlled, Flexible Dose Study Evaluating the Effects of [Vortioxetine] Lu AA21004 Versus Agomelatine in Adult Patients Suffering From Major Depressive Disorder With Inadequate Response to Antidepressant Treatment
- ClinicalTrials.gov ID
- NCT01488071
- Acronym / sponsor ID
- REVIVE / 14178A
- Conditions
- Major Depressive Disorder
- Keywords
- Depression, Multimodal antidepressant
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 495 participants (actual)
- Lead sponsor
- H. Lundbeck A/SIndustry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- Dec 2012 (actual)
- First posted
- 8 Dec 2011 (estimated)
- Results
- Posted 26 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of the present study is to evaluate whether vortioxetine (10 or 20 mg/day) is at least as effective as agomelatine (25 to 50 mg/day) in patients with depressive symptoms that showed inadequate response to Serotonin Reuptake Inhibitors (SRI) antidepressants.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vortioxetine 10 mg or 20 mg | Experimental | Drug: Vortioxetine (Lu AA21004) |
| Agomelatine 25 mg or 50 mg | Active comparator | Drug: Agomelatine |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- The patient is being treated with a serotonin reuptake inhibitor (SRI) antidepressant (monotherapy) that was prescribed to treat Major Depressive Episode (DSM-IV-TR criteria)
- The response to the current SRI treatment is inadequate and patient agrees to discontinue the current SRI at the baseline
- Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥22 at the Screening Visit and Baseline
- The patient, if a woman, must: agree not to try to become pregnant during the study, AND use adequate, highly effective contraception
Key exclusion criteria (4 listed)
- The patient has any current Axis I disorders (DSM-IV criteria) other than Major Depressive Disorder (MDD), General Anxiety Disorder (GAD) and Social Anxiety Disorder (SAD)
- The patient is at significant risk of suicide
- The patient is currently receiving formal psychotherapy or other psychoactive medications
- Other protocol-defined inclusion and exclusion criteria may apply.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vortioxetine (Lu AA21004)Also: Brintellix®encapsulated tablets, daily, orally | Drug | Vortioxetine 10 mg or 20 mg |
| AgomelatineAlso: Valdoxan®encapsulated tablets, daily, orally | Drug | Agomelatine 25 mg or 50 mg |
Primary outcome
Change From Baseline in MADRS Total Score at Week 8
Time frame: Baseline and Week 8
The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 (no symptom) to 6 (severe symptom). The 10 items represent the core symptoms of depressive illness. The rating should be based on a clinical interview with the patient, moving from broadly phrased questions about symptoms to more detailed ones, which allow a precise rating of severity, covering the last 7 days. Total score from 0 to 60. The higher the score, the more severe, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in symptoms.
13 secondary outcomes
Change From Baseline in MADRS Total Score at Week 12
Time frame: Baseline and Week 12
Change From Baseline in HAM-A Total Score at Week 8
Time frame: Baseline and Week 8
Change From Baseline in HAM-A Total Score at Week 12
Time frame: Baseline and Week 12
Change From Baseline in CGI-S Score at Week 8
Time frame: Baseline and Week 8
Change From Baseline in CGI-S Score at Week 12
Time frame: Baseline and Week 12
Change in Clinical Status Using CGI-I Score at Week 8
Time frame: Week 8
Change in Clinical Status Using CGI-I Score at Week 12
Time frame: Week 12
Proportion of Patients Who Respond at Week 8 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)
Time frame: Baseline and Week 8
Proportion of Patients Who Respond at Week 12 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline)
Time frame: Baseline and Week 12
Proportion of Patients Who Are in Remission at Week 8 (Remission is Defined as a MADRS Total Score <=10)
Time frame: Week 8
Proportion of Patients Who Are in Remission at Week 12 (Remission is Defined as a MADRS Total Score <=10)
Time frame: Week 12
Change From Baseline in SDS Total Score at Week 8
Time frame: Baseline and Week 8
Change From Baseline in SDS Total Score at Week 12
Time frame: Baseline and Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36708956Adair M, Christensen MC, Florea I, Loft H, Fagiolini A. Vortioxetine in patients with major depressive disorder and high levels of anxiety symptoms: An updated analysis of efficacy and tolerability. J Affect Disord. 2023 May 1;328:345-354. doi: 10.1016/j.jad.2023.01.074. Epub 2023 Jan 26.
- Derived from this study: PubMed 29554497Papakostas GI, Nielsen RZ, Dragheim M, Tonnoir B. Efficacy and tolerability of vortioxetine versus agomelatine, categorized by previous treatment, in patients with major depressive disorder switched after an inadequate response. J Psychiatr Res. 2018 Jun;101:72-79. doi: 10.1016/j.jpsychires.2018.02.017. Epub 2018 Feb 22.
- Derived from this study: PubMed 25087600Montgomery SA, Nielsen RZ, Poulsen LH, Haggstrom L. A randomised, double-blind study in adults with major depressive disorder with an inadequate response to a single course of selective serotonin reuptake inhibitor or serotonin-noradrenaline reuptake inhibitor treatment switched to vortioxetine or agomelatine. Hum Psychopharmacol. 2014 Sep;29(5):470-82. doi: 10.1002/hup.2424.
Related trials for Major Depressive Disorder
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingPhase 2
Psilocybin With Pimavanserin Compared to Psilocybin Alone for the Treatment of Major Depressive Disorder
Major Depressive Disorder
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Email contact via H. Lundbeck A/S study director
LundbeckClinicalTrials@lundbeck.com
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vortioxetine (Lu AA21004) and Agomelatine in people with Major Depressive Disorder, run by H. Lundbeck A/S.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in MADRS Total Score at Week 8 (time frame: Baseline and Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01488071, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2014; AzTrials last refreshed its copy on 7 Nov 2026.