Major Depressive DisorderPhase 4PoETNCT06103760
Positioning of Esketamine Treatment in the Real-world Management of Depression
A Phase 4 study testing Esketamine Nasal Spray [Spravato] in people with Major Depressive Disorder, run by Royal North Shore Hospital at 1 site in Australia.
Trial summary
The goal of this naturalistic, open label, single arm intervention study is to investigate the effects of Esketamine in treating depression.The main aims to answer are: to investigate whether Esketamine is effective when added to ongoing antidepressant treatment to identify patient characteristics that will determine… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Esketamine Nasal Spray [Spravato]
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 162 participants
- Where
- 1 siteAustralia
- Study dates
- 31 Oct 2023to 15 Aug 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults aged 18-65 years old
- Diagnosis of Major Depressive Disorder (MDD)
- Currently depressed
- Had an inadequate response to 2 or more courses of antidepressants (of adequate dose and duration)
- Be maintained on their current antidepressant medication or psychological therapy at the time of enmrolment
- Able to understand and provide informed consent
Who cannot join
- Concurrent diagnoses:
- Participants with other 'Diagnostic and Statistical Manual of Mental Disorders' (DSM-5) e.g., current substance misuse disorder, bipolar disorder, schizophrenia
- Participants who are unable to understand the study and therefore unable to provide informed consent
- 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
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- 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
- 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.
- 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.
- 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-methamphetamine (MDMA), or other hallucinogen use history
- Participants with hypersensitivity to Esketamine, Ketamine, or any of the excipients
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Yan Yau Wong contact
Australia1 site, 1 recruiting
- Recruiting
Royal North Shore Hospital
St Leonards, New South Wales, 2065
Erica Bell, 02 9462 9905, NSLHD-researchpoet@health.nsw.gov.au
Yan Yau Wong, NSLHD-researchpoet@health.nsw.gov.au
About this study
The goal of this naturalistic, open label, single arm intervention study is to investigate the effects of Esketamine in treating depression.The main aims to answer are:
- to investigate whether Esketamine is effective when added to ongoing antidepressant treatment
- to identify patient characteristics that will determine a therapeutic response to Esketamine in real-world practice
Participants will:
- attend the clinic for supervised self-administration of intranasal Esketamine treatment
- be observed for 2 hours following Esketamine administration including blood pressure monitoring
- be asked to complete a battery of questionnaires
- be reimbursed for travel expenses
Read the detailed description
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.
- Conditions
- Major Depressive Disorder
- Being tested
- Esketamine Nasal Spray [Spravato]
- Keywords
- Depression
- 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.
Esketamine Nasal Spray [Spravato]Drug
Also called Spravato
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.
| Study group | Role | What they receive |
|---|---|---|
| Participants with Major Depressive Disorder | Other | Intranasal esketamine to be self-administered by participants under direct supervision of a healthcare professional. First initial dose is 56mg and subsequent doses will be 56mg or 84mg. Esketamine will be administered twice weekly for weeks 1-4, once weekly for weeks 5-8, and 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 base on tolerability, treatment response, and ongoing consent. Receives: Drug: Esketamine Nasal Spray [Spravato] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of treatment responders determined by a 50% reduction on the Hamilton Depression Rating Scale (HAM-D) 17-Item scoring.
Hamilton Depression Rating Scale (HAM-D) 17-Item scoring
Measured: At the end of week 4
Mean depression score on the Quick Inventory of Depressive Symptomatology Self-report (QIDS-SR) 16-Item.
Quick Inventory of Depressive Symptomatology Self-report (QIDS-SR) 16-Item.
Measured: Baseline, 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.
Global functioning determined by Clinical Global Impression (CGI) score.
Clinical Global Impression (CGI)
Measured: Baseline, week 1, week 2, week 3, week 4 (primary time point), week 8 and week 12 after Esketamine was commenced.
Secondary outcomes (3)
Change in mood symptom scores assessed using the visual analogue scale (self-reported)
Visual analogue scale (self-reported)
Measured: Baseline, after treatment day 1 and day 3 of each week until Esketamine is ceased.
Depressive symptoms assessed using the Beck Depression Inventory (BDI) 21-Item.
Beck Depression Inventory (BDI) 21-Item.
Measured: Baseline and at week 4 after Esketamine was commenced.
Anxiety symptoms assessed using the State-Trait Anxiety Inventory (STAI)
State-Trait Anxiety Inventory (STAI)
Measured: Baseline and at week 4 after Esketamine was commenced.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2023
- Study start31 Oct 2023
- Primary completion15 Dec 2027 (estimated)
- Study completion15 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 162 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal North Shore Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen-Cilag Pty Ltd
- Responsible party
- Principal investigator, Gin Malhi, Royal North Shore Hospital
- Investigators
- Gin Malhi, Principal investigator, Royal North Shore Hospital, University of Sydney
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06103760
- Sponsor's protocol ID
- 2023/PID01587
- Acronym
- PoET
- Status last verified
- Aug 2026
- First submitted
- 15 Oct 2023
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Positioning of Esketamine Treatment in the Real-world Management of Depression
- ClinicalTrials.gov ID
- NCT06103760
- Acronym / sponsor ID
- PoET / 2023/PID01587
- Conditions
- Major Depressive Disorder
- Keywords
- Depression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 162 participants (estimated)
- Lead sponsor
- Royal North Shore HospitalUniversity, hospital or other
- Collaborators
- Janssen-Cilag Pty Ltd
- Study start
- 31 Oct 2023 (actual)
- Primary completion
- 15 Dec 2027 (estimated)
- Study completion
- 15 Aug 2028 (estimated)
- First posted
- 27 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this naturalistic, open label, single arm intervention study is to investigate the effects of Esketamine in treating depression.The main aims to answer are:
- to investigate whether Esketamine is effective when added to ongoing antidepressant treatment
- to identify patient characteristics that will determine a therapeutic response to Esketamine in real-world practice
Participants will:
- attend the clinic for supervised self-administration of intranasal Esketamine treatment
- be observed for 2 hours following Esketamine administration including blood pressure monitoring
- be asked to complete a battery of questionnaires
- be reimbursed for travel expenses
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants with Major Depressive Disorder | Other | Drug: Esketamine Nasal Spray [Spravato]Intranasal esketamine to be self-administered by participants under direct supervision of a healthcare professional. First initial dose is 56mg and subsequent doses will be 56mg or 84mg. Esketamine will be administered twice weekly for weeks 1-4, once weekly for weeks 5-8, and 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 base on tolerability, treatment response, and ongoing consent. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adults aged 18-65 years old
- Diagnosis of Major Depressive Disorder (MDD)
- Currently depressed
- Had an inadequate response to 2 or more courses of antidepressants (of adequate dose and duration)
- Be maintained on their current antidepressant medication or psychological therapy at the time of enmrolment
Key exclusion criteria (22 listed)
- Concurrent diagnoses:
- Pregnancy:
- Current medications:
- Stimulants
- Medical history:
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 |
|---|---|---|
| Esketamine Nasal Spray [Spravato]Also: SpravatoThis 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. | Drug | Participants with Major Depressive Disorder |
Primary outcome
Percentage of treatment responders determined by a 50% reduction on the Hamilton Depression Rating Scale (HAM-D) 17-Item scoring.
Time frame: At the end of week 4
Hamilton Depression Rating Scale (HAM-D) 17-Item scoring
Mean depression score on the Quick Inventory of Depressive Symptomatology Self-report (QIDS-SR) 16-Item.
Time frame: Baseline, 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.
Quick Inventory of Depressive Symptomatology Self-report (QIDS-SR) 16-Item.
Global functioning determined by Clinical Global Impression (CGI) score.
Time frame: Baseline, week 1, week 2, week 3, week 4 (primary time point), week 8 and week 12 after Esketamine was commenced.
Clinical Global Impression (CGI)
3 secondary outcomes
Change in mood symptom scores assessed using the visual analogue scale (self-reported)
Time frame: Baseline, after treatment day 1 and day 3 of each week until Esketamine is ceased.
Depressive symptoms assessed using the Beck Depression Inventory (BDI) 21-Item.
Time frame: Baseline and at week 4 after Esketamine was commenced.
Anxiety symptoms assessed using the State-Trait Anxiety Inventory (STAI)
Time frame: Baseline and at week 4 after Esketamine was commenced.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Individual participant dataSharing planned: No
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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.
Yan Yau Wong contact
Gin Malhi principal investigator
Royal North Shore Hospital, University of Sydney
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Esketamine Nasal Spray [Spravato] in people with Major Depressive Disorder, run by Royal North Shore Hospital at 1 site in Australia.
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 6 inclusion and 22 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: looking for participants now, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Erica Bell (02 9462 9905, NSLHD-researchpoet@health.nsw.gov.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of treatment responders determined by a 50% reduction on the Hamilton Depression Rating Scale (HAM-D) 17-Item scoring. (time frame: At the end of week 4). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Aug 2026.