Ketamine As an Adjunctive Therapy for Major Depression - a Randomised Controlled Trial: [KARMA-Dep (2)]
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 1
- 主要终点
- Montgomery Asberg Depression Rating Scale-10 item version (MADRS)
研究概览
简要总结
Pragmatic, randomised, controlled, parallel-group, superiority trial of ketamine vs. midazolam as an adjunctive therapy for depression. The main purpose of the trial is to assess the mood-rating score difference between ketamine and midazolam from before the first infusion to 24 hours after the final infusion, supplemented by a 95% confidence interval. There will also be a 24-week follow-up after the final infusion session.
详细描述
Pragmatic, randomised, controlled, parallel-group, superiority trial. Trial participants will be patients admitted to St Patrick's University Hospital for treatment of a major depressive episode. The investigators aim to recruit up to 104 participants who will be eligible for this study and randomly allocate 52 patients to each group. Both participants and assessors will be blind to treatment allocation. Eligible consented participants will be randomly allocated in a 1:1 ratio to a course of up to eight infusions of either ketamine or midazolam twice weekly over up to four weeks. Block randomisation will be independently performed. Physical, psychotomimetic and cognitive outcomes will be monitored before, during and after infusions. During the allocated infusions and follow-up period patients will be monitored for treatment-related adverse events relating to both mental and physical health. Participants will also be followed-up for 24 weeks after the end of the initial randomised treatment and assessment period lasting up to four weeks, in order to identify if and when relapse occurs. During the trial, both groups will continue usual inpatient care as prescribed by their treating team.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •≥18 years old.
- •Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥ 20 at screening and start of the first infusion.
- •Voluntary admission for treatment of an acute depressive episode
- •Meet DSM-5 criteria for a major depressive disorder or bipolar affective disorder (current episode depression). Diagnosis of a major depressive disorder or bipolar affective disorder (DSM-5) will be confirmed by the structured diagnostic Mini International Neuropsychiatric Interview (MINI; updated Version 7 for DSM-5).
排除标准
- •Current involuntary admission.
- •Medical condition rendering unfit for ketamine/midazolam.
- •Currently taking any of the contraindicated medications that may alter the pharmacokinetics of ketamine.
- •Active suicidal intention.
- •Dementia.
- •Lifetime history of schizophrenia or schizoaffective disorder; active anorexia nervosa or bulimia nervosa in the past 12 months; alcohol or other substance use disorder (with the exception of nicotine) in the previous six months; any DSM-5 disorder other than a major depressive episode (unipolar or bipolar) as the primary presenting problem.
- •Electroconvulsive Therapy (ECT) administered within the last two months.
- •Pregnancy, breastfeeding or considering becoming pregnancy whilst on the trial for up to 12 weeks after last dose or inability to confirm use of adequate contraception during the trial.
- •Breastfeeding women.
研究组 & 干预措施
Ketamine
Participants will receive up to a four-week course of twice-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.
干预措施: Ketamine (Drug)
Midazolam
Participants will receive up to a four-week course of twice-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.
干预措施: Midazolam (Drug)
结局指标
主要结局
Montgomery Asberg Depression Rating Scale-10 item version (MADRS)
时间窗: 28 weeks
The MADRS is a validated, 10-item, observer-rated scale that measures the symptoms and severity of depression. The primary outcome measure will be the change from baseline in the MADRS score to 24 hours after the final infusion. MADRS will be completed at screening (prior to randomisation), before and after all infusion sessions (at the following timepoints: -40 (±20) mins before the infusion begins; +60 (±10) mins and +120 (±10) mins after the infusion begins; +24 (±1) hours after the infusion ends) and at the 6, 12 and 24 weeks follow-up time points. Sleep and appetite scores will be carried over from -40 minutes to +60 minutes, +120 minutes, and 24 hours after each infusion. Response to treatment is defined as a ≥50% improvement from baseline MADRS score. Remission is defined as achieving a MADRS score ≤10. For those deemed to be treatment remitters, relapse at follow-up time points is defined as a MADRS score of ≥18.
次要结局
- The Clinician-Administered Dissociative States Scale (CADSS)(4 weeks)
- Observer's Assessment of Alertness/Sedation; responsiveness subscale (OAA/S-R)(4 weeks)
- Patient-Rated Inventory of Side Effects (PRISE)(28 weeks)
- The Brief Psychiatric Rating Scale (BPRS)(4 weeks)
- The Quick Inventory of Depressive Symptoms, self-report version (QIDS-SR)(28 weeks)
- The Montreal Cognitive Assessment (MoCA)(28 weeks)
- Young Mania Rating Scale (YMRS; mood item)(4 week)
- 20-item Physician Withdrawal Checklist (PWC-20)(16 weeks)
- Adverse events (AE) and serious adverse events (SAE) review(28 weeks)
- EuroQol-5 dimensions-5 level scale for health status (EQ-5D-5L)(28 weeks)
- Client Service Receipt Inventory (CSRI)(28 weeks)
- Concomitant Medication(28 weeks)
研究者
Prof Declan McLoughlin
Professor
University of Dublin, Trinity College