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

Official title

Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-Resistant Depression: a Randomised, Rater-blinded Trial

Overview

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

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.

Interventions

• Drug 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
• 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

Primary outcome measures

• Montgomery-Asberg Depression Rating Scale (MADRS) [Time frame: From week 0 to week 4.]

Secondary outcome measures (12)

• Montgomery-Asberg Depression Rating Scale (MADRS) score [Time frame: At week 8, month 4 and month 6]
• Response - Montgomery-Asberg Depression Rating Scale (MADRS) [Time frame: Weeks 4, 8 and months 4 and 6]
• Remission - Montgomery-Asberg Depression Rating Scale (MADRS) [Time frame: Weeks 4, 8 and months 4 and 6]
• DASS-21 [Time frame: Performed weekly from baseline to week 8 inclusive and at 6 month visit.]
• Clinical Global Impression-Improvement (CGI-I) [Time frame: Performed weekly from week 1 to week 4 inclusive, then at week 8 and at 3, 4, 5 & 6 month visits.]
• Clinical Global Impression-Severity (CGI-S) [Time frame: Performed weekly from baseline to week 4 inclusive, then at week 8 and at 3, 4, 5 & 6 month visits.]
• Columbia Suicide Severity Rating Scale (C-SSRS) [Time frame: Performed weekly from baseline to week 4 inclusive, then at week 8 and at 3, 4, 5 & 6 month visits.]
• Speed of response - Clinical Global Impression-Improvement (CGI-I) [Time frame: Performed weekly from week 1 to week 4 inclusive, then at week 8 and at 6 month visits.]
• Psychotomimetic symptoms [Time frame: Through study completion at each treatment visit, up to 6 months]
• Suicide attempts or gestures [Time frame: During 6-month study period]
• Number of Participants with urinary symptoms, as assessed using the Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS) [Time frame: Performed at baseline, week 4, week 8 and at 6 month visit.]
• Cognitive Failure Questionnaire scores (CFQ) [Time frame: Performed at baseline, week 4, week 8 and at 6 month visit.]

Eligibility criteria

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
• MADRS score of ≥20 at study baseline, assessed by certified study rater
• 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
• Any treatment with ketamine or Spravato® within 4 weeks prior to written informed consent for the research study
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Australia · 7 centers

• Royal Prince Alfred Hospital — Camperdown
• Black Dog Institute — Randwick
• Ramsay Clinic Northside — St Leonards
• Ramsay Clinic Lakeside — Warners Bay
• Gold Coast University Hospital — Southport
• Ramsay Clinic Albert Road — Melbourne
• Royal Melbourne Hospital — Parkville

Identifiers

NCT: NCT06278779 · X23-0311

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗