Long-term Pain Modulation by Intravenous Esketamine in Complex Regional Pain Syndrome: a Non-inferiority Study
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change from baseline pain scores
研究概览
简要总结
Intravenous administration of esketamine is an effective recognized therapeutic option in refractory pain in CRPS, which sometimes in at least a part of the patients has a prolonged therapeutic effect. Unfortunately, CRPS literature contains a wide range of ketamine dosing regimens with the result that clinical protocols on dosage and administration are very heterogeneous. The current esketamine regimen in Erasmus MC consists of a 6-day hospital admission for continuous administration. In the Netherlands, both inpatient and outpatient esketamine treatments are offered. Inpatient and outpatient ketamine treatments have never been compared in randomized controlled trials and it is therefore unknown whether these two dosing regimens are equally effective.
The primary objective is to demonstrate non-inferiority of experimental esketamine administration of 6x 1 day per 2 weeks (in total 3 months) as compared with standard esketamine administration of 1x 6 consecutive days. The end of study is at 6 months after the start of the study/treatment.
详细描述
Rationale: Complex regional pain syndrome (CRPS) is a debilitating chronic pain condition of one or more limbs. Its diagnosis is based on (combinations of) underlying pathophysiological mechanisms. Achieving relevant pain relief fails in a significant proportion of CRPS patients. Intravenous administration of esketamine is an effective therapeutic option in refractory pain in CRPS, which in at least a part of the patients has a prolonged therapeutic effect. Unfortunately, CRPS literature contains a wide range of ketamine dosing regimens with the result that clinical protocols on dosage and administration are very heterogeneous. In the Netherlands, both inpatient and outpatient esketamine treatments are offered. The current esketamine regimen in Erasmus MC consists of a 6-day hospital admission for continuous administration; however, logistical boundaries limit this therapy. Esketamine infusions in an outpatient setting might increase flexibility and availability of esketamine treatment. However, inpatient and outpatient ketamine treatments have never been compared in randomized controlled trials and it is therefore unknown whether these two dosing regimens are equally effective.
Objective: The primary objective is to demonstrate non-inferiority of experimental esketamine administration of 6x 1 day per 2 weeks (in total 3 months) as compared with standard esketamine administration of 1x 6 consecutive days at 3 months after the start of the study/treatment. The secondary objective is to assess pain scores till 6 months follow-up, logistical problems, adverse effects, questionnaires, thermography and quantitative sensory testing in both treatment groups.
Study design: Prospective, randomized, non-inferiority study in 60 patients
Study population: Sixty adult patients with chronic pain due to CRPS
Intervention: All patients will receive intravenous esketamine. The standard treatment group receives intravenous esketamine for 6 consecutive days (in hospital). The experimental intervention group visits the outpatient clinic to receive intravenous esketamine in day-care setting every 2 weeks for 3 months.
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
- None
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
- •Meeting the new International Association for the Study of Pain (IASP) diagnostic criteria for CRPS ("the Budapest Criteria) (Harden et al., 2010) or having met the new IASP diagnostic criteria of CRPS ("CRPS with Remission of Some features") (Goebel et al., 2021).
- •Willing and capable to participate in the study.
- •CRPS in one upper extremity and/or CRPS in one lower extremity
- •Treatment in an elective setting.
- •Adequate comprehension of the Dutch language
- •Age ≥ 18 years
排除标准
- •Severe liver disease
- •Psychiatric (schizophrenia, psychosis, delirium, manic depression)
- •Active substance abuse
- •Intoxication with alcohol or other substances
- •Poorly controlled hypertension
- •Unstable angina
- •High-risk coronary vascular disease
- •Heart failure
- •Elevated intracranial pressure
- •Elevated intraocular pressure
- •Thyrotoxicosis
- •Pregnancy
- •Combination with derivates of xanthines (theophylline) or ergometrine
研究组 & 干预措施
Outpatient
The experimental intervention group visits the outpatient clinic to receive intravenous esketamine in day-care setting every 2 weeks for 3 months.
干预措施: S-ketamine infusion outpatient setting (Drug)
Inpatient
The standard treatment group receives intravenous esketamine for 6 consecutive days in hospital.
干预措施: S-ketamine infusion inpatient setting (Drug)
结局指标
主要结局
Change from baseline pain scores
时间窗: Baseline (week 0), During inpatient or outpatient esketamine infusion (week 1 for inpatient protocol / week 1, 3, 5, 7, 9, 11 for outpatient protocol), During telephone consultation (week 1, 3, 5, 7, 9, 11), Follow-up (3 months), End of study (6 months)
Pain intensity measured by Numerical Rating Scale (NRS). Minimum value=0 and maximum value is 10. Higher scores mean a worse outcome.
次要结局
- Change from baseline Thermography(Baseline (week 0) and follow-up visit (week 12))
- Adverse events due to S-ketamine infusion(During inpatient or outpatient esketamine infusion (week 1 for inpatient protocol / week 1, 3, 5, 7, 9, 11 for outpatient protocol), During telephone consultation (week 1, 3, 5, 7, 9, 11))
- Patient-Reported Outcomes Measurement Information System (PROMIS) -29 Profile(Baseline (week 0) and follow-up visit (3 months))
- Short-form McGill Pain Questionnaire-2(Baseline (week 0) and follow-up visit (3 months))
- Change from baseline pain medication dose(Baseline (week 0), follow-up visit (3 months) and end of study (6 months))
- Change from baseline Complex Regional Pain Syndrome severity score(Baseline (week 0) and follow-up visit (3 months))
- Pain Self-Efficacy Questionnaire(Baseline (week 0) and follow-up visit (3 months))
- Change from baseline Quantitative Sensory Testing(Baseline (week 0) and follow-up visit (week 12))
- Global Perceived Effect(During telephone consultation (week 1, 3, 5, 7, 9, 11), follow-up visit (3 months) and end of study (6 months))
- Pain Catastrophizing Scale(Baseline (week 0) and follow-up visit (3 months))
- EQ-5D-5L.(Baseline (week 0) and follow-up visit (3 months))
研究者
Thomas J. P. Mangnus, MD
Medical doctor
Erasmus Medical Center