Intensified treatment for major depressive disorder after first treatment failure
A Randomised, Controlled Trial to Investigate the Effect of a Sixweek Intensified Pharmacological Treatment for Major Depressive Disorder Compared to Treatment as Usual in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment.
This study is testing a stronger six-week treatment using esketamine nasal spray and other antidepressants for people with major depressive disorder who didn't get better with their first treatment.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 418 (estimated) |
| Ages | 18 Years to 65 Years |
| Sex | All |
| Sponsor | UMC Utrecht Academic / other |
| Locations | 12 sites (Innsbruck and 11 other locations) |
| Trial ID | NCT05973851 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the effects of a six-week intensified pharmacological treatment for patients with major depressive disorder (MDD) who have experienced a first treatment failure. The study compares this intensified approach using esketamine nasal spray and other antidepressants to the standard treatment as usual. Participants will be closely monitored to assess the efficacy of the new treatment regimen in improving depressive symptoms. The trial aims to provide a more effective treatment option for individuals struggling with treatment-resistant depression.
Who should consider this trial
Good fit: Ideal candidates for this study are adults aged 18 to 65 who have a primary diagnosis of major depressive disorder and have experienced a first treatment failure with their first-line antidepressant.
Not a fit: Patients who have not yet tried any antidepressant or those with psychotic features in their depression may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could offer a more effective treatment strategy for patients with major depressive disorder who have not responded to initial therapies.
How similar studies have performed: Previous studies have shown promising results with esketamine for treatment-resistant depression, indicating that this approach may be effective.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. In- or outpatients, at least 18 years of age up until 65.
2. Being willing and able to provide written informed consent. Having a legal guardian to cosign is allowed. Informed consent will be signed at visit 1, before any study procedure.
3. Female subjects of child bearing potential must use effective contraception during the trial as per the requirements of the applicable SmPCs and should have a negative pregnancy test at visit 1 or 2 (before randomisation).
4. Meeting diagnostic criteria for a primary diagnosis of major depressive disorder (without psychotic features), according to DSM-5. The primary diagnosis will be confirmed by the Mini International Neuropsychiatric Interview (MINI v7.0.2).
5. Subject experiences a treatment failure due to lack of efficacy in the current episode, as confirmed by a CGI-I ≥3; perferably, this treatment is a first-line pharmacotherapeutic agent for the primary DSM-5 diagnosis, and was prescribed for at least 4 weeks within an effective dose range as specified in the Summary of Product Characteristics (SmPCs).
6. Subject and clinician intend to change pharmacotherapeutic treatment. However, other lines of treatment are allowed as well.
7. A minimum symptom severity threshold needs to be present (moderate level; see below) and subject needs to experience functional impairment.
* The minimum symptom severity threshold is a score of ≥20 on the Montgomery Åsberg Depression Rating Scale (MADRS)
* Functional impairment is defined as a score of 5 or higher on any of the three scales of the Sheehan Disability Scale (SDS).
Exclusion criteria:
1. Being pregnant or breastfeeding.
2. Subject has used (es)ketamine previously for the treatment of depressive symptoms.
3. Subject has a known intolerance to (es)ketamine or to all TAU medication.
4. Meeting any of the contraindications for (es)ketamine, or to all TAU medication options, as specified within the applicable SmPC, supported by clinically significant abnormal values on local laboratory tests, electrocardiogram (ECG) or physical examinations.
5. Subject has participated in another clinical trial in which the subject received an experimental or investigational drug or agent within 30 days before visit 1.
6. Subject experiences any other significant disease or disorder which, in the opinion of the investigator, may either put the subjects at risk because of participation in the trial, or may influence the result of the trial, or the subject's ability to participate in the trial.
7. Subjects with active suicidal ideation with some intent to act, without specific plan ("Yes" to question 4 of the Columbia-Suicide Severity Rating Scale (C-SSRS)) or active suicidal ideation with specific plan and intent ("Yes" to question 5 of the C-SSRS), followed by an assessment by the treating clinician who determines it is not safe for the subject to participate in the study
8. Subject meets criteria for current substance use disorder, as confirmed by the Mini International Neuropsychiatric Interview (MINI v7.0.2). Nicotine dependency is allowed, as well as mild and moderate alcohol and/or cannabis use disorder (as defined by MINI v7.0.2). Severe alcohol and/or cannabis use disorder are not allowed.
9. Subjects have not been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
10. Subjects dependent on the sponsor, investigator or trial site must be excluded from participation in advance.
Where this trial is running
Innsbruck and 11 other locations
- Medical University Innsbruck — Innsbruck, Austria (Recruiting)
- Universitätsklinik für Psychiatrie und Psychotherapie Bielefeld — Bielefeld, Germany (Recruiting)
- LWL-Klinik Dortmund, Bereich Forschung & Wissenschaft — Dortmund, Germany (Recruiting)
- University Hospital Frankfurt am Main - Goethe University — Frankfurt am Main, Germany (Recruiting)
- Westfälische Wilhelms-Universität Münster — Münster, Germany (Recruiting)
- Eginition Hospital, department of psychiatry — Athens, Greece (Not_yet_recruiting)
- Universita degli Studi di Brescia — Brescia, Italy (Not_yet_recruiting)
- University of Cagliari — Cagliari, Italy (Recruiting)
- Università degli studi della Campania Luigi Vanvitelli — Naples, Italy (Recruiting)
- Azienda Ospedaliero-Universitaria "Città della Salute e della Scienza di Torino" — Turin, Italy (Not_yet_recruiting)
- Fundació Clínic per a la Recerca Biomèdica — Barcelona, Spain (Recruiting)
- King's College London, Psychiatry & Cognitive Neuroscience — London, United Kingdom (Not_yet_recruiting)
Study contacts
- Study coordinator: Inge Winter, Dr.
- Email: i.winter@umcutrecht.nl
- Phone: +31875553227
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.