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

NCT06278779 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: X23-0311
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Treatment Resistant Depression

Outcome Measures

Primary Outcomes (1)

• Montgomery-Asberg Depression Rating Scale (MADRS)

  Change in score on the Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS is sensitive to change, and is commonly used for treatment trials in depression. MADRS includes questions on ten symptoms, each of which yields a score of 0 to 6. The total score ranges from 0 to 60. The higher the MADRS score the more severe the depression. Cutoff points are for levels of depression are: 0 to 6: normal /symptom absent 7 to 19: mild depression 20 to 34: moderate depression 35 to 60: severe depression.

  From week 0 to week 4.

Secondary Outcomes (25)

• Montgomery-Asberg Depression Rating Scale (MADRS) score

  At week 8, month 4 and month 6

• Response - Montgomery-Asberg Depression Rating Scale (MADRS)

  Weeks 4, 8 and months 4 and 6

• Remission - Montgomery-Asberg Depression Rating Scale (MADRS)

  Weeks 4, 8 and months 4 and 6

• DASS-21

  Performed weekly from baseline to week 8 inclusive and at 6 month visit.

• Clinical Global Impression-Improvement (CGI-I)

  Performed weekly from week 1 to week 4 inclusive, then at week 8 and at 6 month visits.

Study Arms (2)

Esketamine group

ACTIVE COMPARATOR

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.

Drug: Esketamine group

Racemic ketamine

ACTIVE COMPARATOR

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. .

Drug: Racemic ketamine

Interventions

Esketamine group 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

Also known as: Spravato®

Esketamine group

Racemic ketamine 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

Racemic ketamine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The George Institute: lead
• The University of New South Wales: collaborator

Study Sites (6)

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

RECRUITING

Black Dog Institute

Randwick, New South Wales, 2031, Australia

RECRUITING

Ramsay Clinic Northside

St Leonards, New South Wales, 2065, Australia

RECRUITING

Ramsay Clinic Lakeside

Warners Bay, New South Wales, 2282, Australia

RECRUITING

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

RECRUITING

Ramsay Clinic Albert Road

Melbourne, Victoria, 3004, Australia

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Esketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Colleen Loo

  The University of New South Wales

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abigail Hansen

CONTACT

80524300; Trek@georgeinstitute.org.au

Fay Wang

CONTACT

80524300; Trek@georgeinstitute.org.au

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Primary outcome raters will be blinded to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, prospective, parallel group, comparative effectiveness trial.

Study Record Dates

• First Submitted: January 20, 2024
• First Posted: February 26, 2024
• Study Start: June 3, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: June 3, 2025

Record last verified: 2025-05

Locations

AU (6)