The Effect of a Four Week Intensified... — Clinical Trial Details

The Effect of a Four Week 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. (INTENSIFY MDD)

Open-label, randomised, parallel trial with blinded raters (n=418) comparing early-intensified pharmacological treatment including esketamine or ketamine (twice-weekly for 4 weeks) plus a second-line antidepressant versus treatment as usual in adults (18–65) with MDD and first-line treatment failure.

Detailed Description

Rationale: MDD is common and treatment selection is often trial-and-error; early intensified treatment with (es)ketamine may prevent progression to treatment-resistant illness and reduce burden and costs.

Objective: To compare symptom severity change at six weeks (MADRS) between early-intensified pharmacological treatment (EIPT) and treatment as usual (TAU) in adults with MDD and first-line treatment failure.

Design: International, multicentre, randomised, open-label, parallel trial with blinded outcome assessors; participants randomised to EIPT (second-line antidepressant plus esketamine nasal spray or (es)ketamine/ketamine IV twice weekly for 4 weeks) or TAU (second-line antidepressant per physician).

Safety and monitoring: Standard safety measures (labs, ECG, vitals) and a 2-hour observation after each (es)ketamine/ketamine administration; adverse events recorded with standardized scales (GASE) and routine procedures.

Participants

Ages

18 – 65

Sexes

Male & Female

BMI

Psychosis History

Inclusion Criteria

In- or outpatients, at least 18 years of age up until 65.
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.
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).
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).
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).
Subject and clinician intend to change pharmacotherapeutic treatment. However, other lines of treatment are allowed as well.
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

Being pregnant or breastfeeding.
Subject has used (es)ketamine previously for the treatment of depressive symptoms.
Subject has a known intolerance to (es)ketamine or to all TAU medication.
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.
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.
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.
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
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.
Subjects have not been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
Subjects dependent on the sponsor, investigator or trial site must be excluded from participation in advance.

Company

Product

Legal

The Effect of a Four Week 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. (INTENSIFY MDD)

Detailed Description

Study Protocol

Preparation

Locations

Dosing

Integration

Study Arms & Interventions

EIPT

Interventions

TAU

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details

Study Team

Sponsors & Collaborators