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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

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

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 groups in NCT01488071
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.

Jan 2012Dec 2012

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)

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 36708956
Papakostas 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 29554497
Montgomery 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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)

All Major Depressive Disorder trials

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.

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

Results posted to the registry on 26 Mar 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Vortioxetine 10 mg or 20 mg	253	200
Agomelatine 25 mg or 50 mg	242	179

Primary outcome: Change From Baseline in MADRS Total Score at Week 8

Time frame: Baseline and Week 8. Mean (Standard Error). Unit: units on a scale

Measure	Vortioxetine 10 mg or 20 mg n = 220	Agomelatine 25 mg or 50 mg n = 190
Value	-16.53 (0.48)	-14.38 (0.51)

Vortioxetine 10 mg or 20 mg vs Agomelatine 25 mg or 50 mg: Mean Difference (Final Values): -2.16 (95% CI -3.51 to -0.81), p = 0.0018, Mixed Models Analysis

Population analysed: full-analysis set (FAS)

13 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Vortioxetine	3 of 253 (1.2%)	82 of 253 (32.4%)	Not reported
Agomelatine	4 of 242 (1.7%)	77 of 242 (31.8%)	Not reported

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

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
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)

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.