Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-Resistant Depression: a Randomised, Rater-blinded Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 162
- 试验地点
- 13
- 主要终点
- Montgomery-Asberg Depression Rating Scale (MADRS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Primary outcome raters will be blinded to treatment allocation.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Esketamine group (Drug)
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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干预措施: Racemic ketamine (Drug)
结局指标
主要结局
Montgomery-Asberg Depression Rating Scale (MADRS)
时间窗: From week 0 to week 4.
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.
次要结局
- 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.)
- Clinical Global Impression-Severity (CGI-S)(Performed weekly from baseline to week 4 inclusive, then at week 8 and at 6 month visits.)
- Columbia Suicide Severity Rating Scale (C-SSRS)(Performed weekly from baseline to week 4 inclusive, then at week 8 and at 6 month visits.)
- Speed of response - Clinical Global Impression-Improvement (CGI-I)(Performed weekly from week 1 to week 4 inclusive, then at week 8 and at 6 month visits.)
- Psychotomimetic symptoms(Through study completion at each treatment visit, up to 6 months)
- Suicide attempts or gestures(During 6-month study period)
- Number of Participants with urinary symptoms, as assessed using the Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS)(Performed at baseline, week 4, week 8 and at 6 month visit.)
- Cognitive Failure Questionnaire scores (CFQ)(Performed at baseline, week 4, week 8 and at 6 month visit.)
- Ketamine liking/craving score(Performed at baseline, week 4, week 8 and at 6 month visit.)
- Number of Participants with urinary symptoms, as assessed using the Ketamine Side Effect Tool (KSET)(Through study completion at each treatment visit, up to 6 months)
- Acceptability Questionnaire(Performed at week 4, week 8 and at 6 month visit.)
- End of Treatment questionnaire(Used at end of the treatment period(s) over the course of the study.)
- Recovering Quality of Life Questionnaire (REQOL-10)(Over 6 month study period)
- WHO Disability Assessment Scale (WHODAS-12)(Over 6 month study period)
- Patient Health Questionnaire-9 (PHQ-9)(Over 6 month study period)
- Assessment of Quality of Life Questionnaire (AQoL-8D)(Over 6 month study period)
- Resource Use Questionnaire (RUQ)(Over 6 month study period)
- Treatment Preference(Assessed once, prior to randomization)
- Stanford Expectations of Treatment Scale (SETS)(Assessed once, after randomization and before first treatment)
- Difficulties in Emotion Regulation Scale-16 (DERS-16)(Performed at baseline and week 4)
- Level of Personality Functioning Scale-Brief Form (LPFS-BF)(Performed at baseline and week 4)