Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-resistant Depression

NCT ID: NCT06278779

Last Updated: 2025-06-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

162 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-03

Study Completion Date

2027-04-30

Brief Summary

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The goal of this study is to compare the effectiveness of two formulations of ketamine - Spravato® and racemic ketamine - in people with treatment-resistant depression (TRD). The main questions it aims to answer are:

* How the two formulations compare in terms of their effectiveness in treating TRD.
* How the two formulations compare in their acceptability to patients, safety, effects on patient quality of life and function, and cost effectiveness.

Participants will be randomised to receive either Spravato® or racemic ketamine treatment and asked to complete some questionnaires to assess the effects on mood, treatment acceptability, side effects, quality of life and function, and health economic outcomes.

Detailed Description

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The TREK study is a randomized, prospective, rater blinded (primary outcome raters), parallel group, comparative effectiveness trial of racemic ketamine and Spravato®, comparing their effectiveness, acceptability, safety, effects on quality of life (QOL), function and cost effectiveness after 4 weeks - 6 months of treatment in people with TRD.

Participants will be recruited from clinics/hospitals that are providing racemic ketamine and Spravato® treatment services for TRD. Participants will be referred, treated and followed up as per the clinic's normal clinical practice. Participants who consent to participate in this research study will undergo other processes in addition to the standard treatment procedures provided by their clinic:

* Randomisation to receive racemic ketamine or Spravato®.
* Completion of questionnaires to measure treatment effects on mood, acceptability, safety, quality of life and function and cost effectiveness.

Conditions

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Treatment Resistant Depression

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized, prospective, parallel group, comparative effectiveness trial.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Primary outcome raters will be blinded to treatment allocation.

Study Groups

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Esketamine group

Dosing of esketamine intranasal spray will be guided by the Spravato® Product Information. This involves a starting dosage of 28 or 56 mg, with dose adjustment up to 84 mg as required to optimise response. Dose adjustments will be based on effectiveness and tolerability to the previous dose. The recommended treatment protocol is twice per week for 4 weeks, then weekly in weeks 5-8, then option of weekly-fortnightly "maintenance" treatment for responders. After week 8, patients may continue treatment as guided by the ketamine clinic psychiatrist.

Group Type ACTIVE_COMPARATOR

Esketamine group

Intervention Type DRUG

The recommended dosing for Spravato is:

Weeks 1-4:

Starting Day 1 dose:

\< 65 years: 56 mg

≥ 65 years: 28 mg

Subsequent doses:

28 mg (≥ 65 years), 56 mg or 84 mg twice weekly

Weeks 5-8:

28 mg (≥ 65 years), 56 mg or 84 mg once weekly

From Week 9:

28 mg (≥ 65 years), 56 mg or 84 mg every 2 weeks or once weekly

Racemic ketamine

Treatment administration will follow standard clinical practice in the recruiting clinic, with a recommendation to follow an evidence-based and established dose-optimising approach, given by injection, twice per week for 4 weeks, then the frequency of further treatments (week 5 - month 6) will be based on the clinical judgement of the ketamine clinic psychiatrist.

Dosing will be adjusted by the ketamine clinic psychiatrist, based on clinical response, safety and tolerability. The psychiatrist will review the patient before each treatment, over the first 4 weeks, to judge the dose level required.

Typically, dosing will begin at the standard dose of 0.5 mg/kg and adjusted using an ascending dose titration schedule if the patient has not shown clinical response and if side effects are adequately tolerated.

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Group Type ACTIVE_COMPARATOR

Racemic ketamine

Intervention Type DRUG

Typically, dosing will begin at the standard dose of 0.5 mg/kg and adjusted as needed using an ascending dose titration schedule:

1. 0.5 mg/kg
2. 0.6 mg/kg
3. 0.75 mg/kg
4. 0.9 mg/kg
5. Further increments by 0.1-0.2 mg/kg, up to max 1.5 mg/kg

Interventions

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Esketamine group

The recommended dosing for Spravato is:

Weeks 1-4:

Starting Day 1 dose:

\< 65 years: 56 mg

≥ 65 years: 28 mg

Subsequent doses:

28 mg (≥ 65 years), 56 mg or 84 mg twice weekly

Weeks 5-8:

28 mg (≥ 65 years), 56 mg or 84 mg once weekly

From Week 9:

28 mg (≥ 65 years), 56 mg or 84 mg every 2 weeks or once weekly

Intervention Type DRUG

Racemic ketamine

Typically, dosing will begin at the standard dose of 0.5 mg/kg and adjusted as needed using an ascending dose titration schedule:

1. 0.5 mg/kg
2. 0.6 mg/kg
3. 0.75 mg/kg
4. 0.9 mg/kg
5. Further increments by 0.1-0.2 mg/kg, up to max 1.5 mg/kg

Intervention Type DRUG

Other Intervention Names

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Spravato®

Eligibility Criteria

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Inclusion Criteria

* Adult with treatment-resistant depression (TRD: not responded adequately to at least two different antidepressants of adequate dose and duration) who has a current depressive episode (DSM 5)
* Assessed and attested by clinic psychiatrist as appropriate to receive either racemic ketamine or Spravato® ketamine treatment for TRD
* Aged ≥18 years
* Written informed consent for research study obtained

Exclusion Criteria

* Not able to give informed consent
* Any physical or mental condition which, in the opinion of the investigator, could interfere with study participation including outcome assessments
* Patients who require an interpreter/translator for the clinic consent process, due to the infeasibility of obtaining an interpreter for research assessments, including self-rated scales
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The University of New South Wales

OTHER

Sponsor Role collaborator

The George Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Colleen Loo

Role: PRINCIPAL_INVESTIGATOR

The University of New South Wales

Locations

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Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Site Status RECRUITING

Black Dog Institute

Randwick, New South Wales, Australia

Site Status RECRUITING

Ramsay Clinic Northside

St Leonards, New South Wales, Australia

Site Status RECRUITING

Ramsay Clinic Lakeside

Warners Bay, New South Wales, Australia

Site Status RECRUITING

Gold Coast University Hospital

Southport, Queensland, Australia

Site Status RECRUITING

Ramsay Clinic Albert Road

Melbourne, Victoria, Australia

Site Status RECRUITING

Countries

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Australia

Central Contacts

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Abigail Hansen

Role: CONTACT

Fay Wang

Role: CONTACT

Facility Contacts

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Nicollette Thornton

Role: primary

Angelo Alonzo

Role: primary

Mayra Ouriques

Role: primary

Sally Sally Wilkinson

Role: primary

Natasha Cairns

Role: backup

Catherine Donald

Role: primary

Melanie Hurley

Role: primary

Other Identifiers

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X23-0311

Identifier Type: -

Identifier Source: org_study_id

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