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Trial registered on ANZCTR


Registration number
ACTRN12623001068651
Ethics application status
Approved
Date submitted
18/09/2023
Date registered
5/10/2023
Date last updated
6/06/2024
Date data sharing statement initially provided
5/10/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Positioning of Esketamine Treatment (PoET) in the real-world management of depression
Scientific title
Evaluating the Positioning of Esketamine Treatment (PoET) for symptom management in adults with major depressive disorder
Secondary ID [1] 309907 0
None
Universal Trial Number (UTN)
Trial acronym
PoET
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder 331214 0
Condition category
Condition code
Mental Health 327979 327979 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is an uncontrolled, single arm, naturalistic study. There will be three treatment phases: Phase 1 - Acute treatment phase (weeks 1-4); Phase 2 - Maintenance treatment phase (weeks 5-8); Phase 3 - Continuation treatment phase (Weeks 9-25). Phase 1 is the critical component of our study as it determines our primary outcomes.
Name of drug: esketamine
Dose: initial first dose is 56mg; subsequent doses will be 56mg or 84mg
Duration: twice weekly for weeks 1-4; once weekly for weeks (5-8); once weekly/once fortnightly/once monthly as clinically indicated for weeks (9-25). After each treatment phase, participants will be re-assessed through a comprehensive battery of assessments and dose adjustments will be performed by the study psychiatrist based on tolerability, treatment response, and ongoing consent.
Mode of administration: intranasal spray; self-administration with direct supervision
Adherence to intervention: The intervention is dispensed and provided within the CADE clinic; therefore, participants' attendance at the clinic is required
Intervention code [1] 326835 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 335845 0
Percentage of treatment responders determined by a 50% reduction on the Hamilton Depression Rating Scale (HAM-D) 17-Item scoring.
Timepoint [1] 335845 0
At the conclusion of the study
Primary outcome [2] 336083 0
Mean depression score on the Quick Inventory of Depressive Symptomatology Self-report (QIDS-SR) 16-Item.
Timepoint [2] 336083 0
Baseline, after first treatment, at the end of weeks 1,2,3, and 4 (primary time point); and further after week 8 and week 12 after Esketamine was commenced.
Primary outcome [3] 336084 0
Global functioning determined by Clinical Global Impression (CGI) score.
Timepoint [3] 336084 0
Baseline, week 1, week 2, week 3, week 4 (primary time point), week 8 and week 12 after Esketamine was commenced.
Secondary outcome [1] 425868 0
Change in mood symptom scores assessed using the visual analogue scale (self-reported).
Timepoint [1] 425868 0
Baseline and following each administration of Esketamine until this is ceased.
Secondary outcome [2] 426783 0
Depressive symptoms assessed using the Beck Depression Inventory (BDI) 21-Item.
Timepoint [2] 426783 0
Baseline and at week 4 after Esketamine was commenced.
Secondary outcome [3] 426784 0
Anxiety symptoms assessed using the State-Trait Anxiety Inventory (STAI)
Timepoint [3] 426784 0
Baseline and at week 4 after Esketamine was commenced.

Eligibility
Key inclusion criteria
1. Be an adult aged 18-65 years old
2. Have a primary diagnosis of Major Depressive Disorder (MDD)
***Please note: a co-morbid diagnosis of an anxiety disorder or ADHD can be included***
3. Be currently depressed and on medication for current episode
4. Have experienced an inadequate response to 2 or more courses of antidepressants (of adequate dose and duration)
5. Be maintained on their current antidepressant medication or psychological therapy at the time of enrolment
6. Able to understand and able to provide informed consent
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Concurrent diagnoses
- Participants with DSM-5 disorders e.g., current substance misuse disorder, bipolar disorder, schizophrenia
- Participants who are unable to understand the study and therefore unable to provide informed consent
2. Pregnancy
- Participants who are pregnant and/or breastfeeding
- Participants who are not willing to avoid pregnancy for themselves or their partners during the study by using effective birth control methods
3. Current medications
- Participants taking a total daily dose of benzodiazepines greater than the equivalent of 6mg/day of lorazepam
- Participants on complementary and alternative medicine therapies i.e., St John’s wort, Chinese medicines, and various herbal and homeopathic treatments
4. Stimulants
- Participants taking stimulants such as methylphenidate, amphetamine, and dextroamphetamine for a diagnosis such as ADHD can still have Esketamine provided they do not continue taking stimulants concurrently for the duration of the study.
- Concurrent use is excluded due to the synergistic effect with Esketamine that can cause increased blood pressure.
5. Medical history
- Participants with current or past history of seizures (uncomplicated childhood febrile seizures with no sequelae are not exclusionary)
- Participants with a history of uncontrolled hypertension
- Participants with uncontrolled diabetes mellitus
- Participants with aneurysmal vascular disease including thoracic and abdominal aorta, intracranial and peripheral arterial vessels, or arteriovenous malformation, intracerebral haemorrhage
- Participants with untreated glaucoma, current penetrating or perforating eye injury, brain injury, hypertensive encephalopathy, intrathecal therapy with ventricular shunts, or any other condition associated with increased intracranial pressure or increased intraocular pressure or planned eye surgery
- Participants who are currently receiving electroconvulsive therapy (ECT) or have received ECT in the past month
6. Substance Misuse History
- Participants who have ever had a substance misuse disorder involving any of the following over their lifetime: ketamine, phencyclidine (PCP), lysergic acid diethylamide (LSD), or 3,4-methylenedioxy-methamhetamine (MDMA), or other hallucinogen use history
- Participants with hypersensitivity to Esketamine, Ketamine, or any of the excipients

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
17/10/2023
Actual
31/10/2023
Date of last participant enrolment
Anticipated
24/03/2025
Actual
Date of last data collection
Anticipated
15/09/2025
Actual
Sample size
Target
162
Accrual to date
11
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 25436 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 41178 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 314089 0
Commercial sector/Industry
Name [1] 314089 0
Janssen-Cilag Pty Ltd
Country [1] 314089 0
Australia
Primary sponsor type
Government body
Name
Northern Sydney Local Health District
Address
Level 14, Kolling Building 10 Westbourne Ave St Leonards NSW 2065
Country
Australia
Secondary sponsor category [1] 316002 0
None
Name [1] 316002 0
Address [1] 316002 0
Country [1] 316002 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313226 0
Northern Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 313226 0
Level 13, Kolling BuildingRoyal North Shore Hospital Reserve Road, St Leonards NSW 2065
Ethics committee country [1] 313226 0
Australia
Date submitted for ethics approval [1] 313226 0
23/06/2023
Approval date [1] 313226 0
01/08/2023
Ethics approval number [1] 313226 0
2023/ETH01392

Summary
Brief summary
Depression is a common mental illness, and it is one of the leading causes of disease burden worldwide. Fortunately, there are many effective treatments available for depression, including lifestyle changes, psychological treatments, and medications such as antidepressants. However, not all patients will respond to the first treatment prescribed. Some patients may only experience a 'partial response', where a few treatments help their depression somewhat, but they do not achieve a full recovery. Currently, the reasons why some patients do not respond, or only experience a partial response to an antidepressant, is not fully understood.
Recently, researchers have been investigating new medications that may help patients recover from depression. One of these new medications is Esketamine, which is a relatively new molecule derived from a drug called Ketamine - an anaesthetic that has been used medically for decades. Researchers have been investigating the antidepressant properties of Ketamine for a long time. It is thought that Ketamine, and its derivative, Esketamine, help to treat depression for a number of reasons. However, it is not yet known which patients benefit most from Esketamine when used in conjunction with conventional antidepressants. In addition, we do not yet understand how the effect of Esketamine is impacted by other treatments that a patient may be taking for their depression. Finally, it has not yet been investigated how patients with a partial response to an antidepressant will benefit from adding Esketamine to their therapeutic regimen without switching to a new baseline antidepressant. Therefore, there are two principle aims of this study 1) to investigate whether Esketamine is effective when added to ongoing antidepressant treatment and 2) to identify patient characteristics that will determine a therapeutic response to Esketamine in real-world practice.

In patients that improve with the addition of Esketamine to their current antidepressant treatment, we hypothesize that their improvement will be determined by their personal characteristics and/or the type of treatment they are already receiving.
Trial website
https://www.cadeclinic.com/poetstudy
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 127414 0
Prof Gin Malhi
Address 127414 0
CADE (Clinical Assessment and Diagnostic Evaluation) Clinic, Level 3, Royal North Shore Hospital, Reserve Road, St Leonards, NSW 2065
Country 127414 0
Australia
Phone 127414 0
+61 2 9462 9909
Fax 127414 0
Email 127414 0
[email protected]
Contact person for public queries
Name 127415 0
Erica Bell
Address 127415 0
CADE (Clinical Assessment and Diagnostic Evaluation) Clinic, Level 3, Royal North Shore Hospital, Reserve Road, St Leonards, NSW 2065
Country 127415 0
Australia
Phone 127415 0
+61 294639905
Fax 127415 0
Email 127415 0
[email protected]
Contact person for scientific queries
Name 127416 0
Erica Bell
Address 127416 0
CADE (Clinical Assessment and Diagnostic Evaluation) Clinic, Level 3, Royal North Shore Hospital, Reserve Road, St Leonards, NSW 2065
Country 127416 0
Australia
Phone 127416 0
+61 294639905
Fax 127416 0
Email 127416 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
20099Ethical approval    386089-(Uploaded-23-08-2023-10-33-40)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.