ANZCTR - Registration

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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]

None

Universal Trial Number (UTN)

Trial acronym

PoET

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Major Depressive Disorder

Condition category

Condition code

Mental Health

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]

Treatment: Drugs

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Percentage of treatment responders determined by a 50% reduction on the Hamilton Depression Rating Scale (HAM-D) 17-Item scoring.

Timepoint [1]

At the conclusion of the study

Primary outcome [2]

Mean depression score on the Quick Inventory of Depressive Symptomatology Self-report (QIDS-SR) 16-Item.

Timepoint [2]

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]

Global functioning determined by Clinical Global Impression (CGI) score.

Timepoint [3]

Baseline, week 1, week 2, week 3, week 4 (primary time point), week 8 and week 12 after Esketamine was commenced.

Secondary outcome [1]

Change in mood symptom scores assessed using the visual analogue scale (self-reported).

Timepoint [1]

Baseline and following each administration of Esketamine until this is ceased.

Secondary outcome [2]

Depressive symptoms assessed using the Beck Depression Inventory (BDI) 21-Item.

Timepoint [2]

Baseline and at week 4 after Esketamine was commenced.

Secondary outcome [3]

Anxiety symptoms assessed using the State-Trait Anxiety Inventory (STAI)

Timepoint [3]

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?

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

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Royal North Shore Hospital - St Leonards

Recruitment postcode(s) [1]

2065 - St Leonards

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Janssen-Cilag Pty Ltd

Address [1]

66 Waterloo RdMacquarie Park NSW 2113

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Northern Sydney Local Health District Human Research Ethics Committee

Ethics committee address [1]

Level 13, Kolling BuildingRoyal North Shore Hospital Reserve Road, St Leonards NSW 2065

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

23/06/2023

Approval date [1]

01/08/2023

Ethics approval number [1]

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

Prof Gin Malhi

Address

CADE (Clinical Assessment and Diagnostic Evaluation) Clinic, Level 3, Royal North Shore Hospital, Reserve Road, St Leonards, NSW 2065

Country

Australia

Phone

+61 2 9462 9909

Fax

gin.malhi@sydney.edu.au

Contact person for public queries

Name

Erica Bell

Address

CADE (Clinical Assessment and Diagnostic Evaluation) Clinic, Level 3, Royal North Shore Hospital, Reserve Road, St Leonards, NSW 2065

Country

Australia

Phone

+61 294639905

Fax

NSLHD-researchpoet@health.nsw.gov.au

Contact person for scientific queries

Name

Erica Bell

Address

CADE (Clinical Assessment and Diagnostic Evaluation) Clinic, Level 3, Royal North Shore Hospital, Reserve Road, St Leonards, NSW 2065

Country

Australia

Phone

+61 294639905

Fax

NSLHD-researchpoet@health.nsw.gov.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
20099	Ethical 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.

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