The Role of Coadministration of Lidocaine and Ketamine in Opioid-Refractory Chronic Cancer-Related Pain: a Randomized, Double-Blinded, Placebo-Controlled, Cross-Over Trial.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Change from Baseline in the Worst Pain During the Last 24 Hours on an 11-Point, 0 to 10, Numerical Rating Scale
研究概览
简要总结
This is a randomized, double-blinded, placebo-controlled, cross-over trial examining the effect of a series of two weekly intravenous infusions of lidocaine 4 mg/kg and ketamine 0.2 mg/kg in patients with moderate to severe opioid-refractory chronic cancer-related pain. The aim of this study is to investigate whether the lidocaine - ketamine (LK) regimen provides better analgesia that an active placebo of midazolam 0.02 mg/kg, in this population.
详细描述
Background
Opioids are the mainstay of treatment for chronic cancer-related pain, but their use is associated with multiple adverse effects, tolerance requiring progressively higher doses, and, in rare cases, opioid-induced hyperalgesia. Standard adjuvant analgesics (antiepileptics and antidepressants) may provide modest benefit. However, despite maximally tolerated therapy, many patients continue to experience refractory pain.
Lidocaine and low-dose ketamine may be beneficial in these difficult-to-treat pain scenarios due to their favorable safety profile and mechanisms of action. The main limitation of these drugs is their short duration of action; however, mechanisms involving central plasticity and reversal of opioid tolerance and opioid-induced hyperalgesia may explain the longer analgesic effects observed in some studies.
Study Design
This is a randomized, double-blind, active placebo-controlled, cross-over trial evaluating the efficacy of two weekly lidocaine-ketamine (LK) infusions compared to active placebo in patients with opioid-refractory chronic cancer-related pain.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •Age 18 years or more
- •Capacity to provide informed consent, ability to complete study assessments and comply with the study procedures
- •Meets the IASP definition for chronic cancer-related pain
- •Moderate or severe pain, defined as average pain of 4 or greater on an 11-point (0-10) NRS in the past 24h
- •Adequate trial of opioid medication, defined as a dose of at least 60 mg/day oral morphine equivalent or maximum tolerated dose, in the past 24h
- •For patients with neuropathic component to pain: adequate trial of at least one adjuvant analgesic, defined as a daily dose of at least Amitriptyline 37.5mg, Duloxetine 30mg, Gabapentin 900mg, Pregabalin 150mg, Venlafaxine 60mg or equivalent (26), or maximum tolerated dose in the past 24h
排除标准
- •Previous adverse reaction to ketamine, lidocaine or other amide-type local anesthetics, midazolam
- •Severe liver disease (Child Class B or C)
- •SGPT or SGOT >5 times the upper limit of normal
- •End stage kidney disease
- •Serious cardiac comorbidity (e.g. unstable angina, poorly controlled hypertension or tachycardia, high-risk coronary vascular disease, symptomatic heart failure with NYHA class III-IV, history of heart block, Wolf-Parkinson-White syndrome, Adams-Stokes syndrome)
- •Elevated intracranial or intraocular pressure
- •Pheochromocytoma or poorly controlled hyperthyroidism
- •History of psychosis, schizophrenia or substance abuse
- •Pregnant or breastfeeding
- •Porphyria
- •Life expectancy shorter than the duration of the study
研究组 & 干预措施
Lidocaine and Ketamine Infusion
干预措施: Lidocaine and Ketamine Infusion (Drug)
Active Placebo (Midazolam) Infusion
干预措施: Active Placebo (Midazolam) Infusion (Drug)
结局指标
主要结局
Change from Baseline in the Worst Pain During the Last 24 Hours on an 11-Point, 0 to 10, Numerical Rating Scale
时间窗: Baseline (immediately before the first LK or placebo infusion) and one week after the second infusion.
Question 3 of the Brief Pain Inventory - Short Form, where 0 is equivalent to no pain and 10 indicates the worst possible pain.
次要结局
- Changes in the Score of Pain Intensity of the Brief Pain Inventory - Short Form(Baseline (before the first LK or placebo infusion), before the second infusion (LK or placebo), and, one week after the second infusion (LK or placebo).)
- Change in the Proportion of Patients Achieving 2-Point Reduction on Worst and Least Pain of the Brief Pain Inventory - Short Form(Baseline (before the first LK or placebo infusion), before the second infusion (LK or placebo), and, one week after the second infusion (LK or placebo).)
- Change in the Score of the Interference Scale of the Brief Pain Inventory - Short Form(Baseline (before the first LK or placebo infusion), before the second infusion (LK or placebo), and, one week after the second infusion (LK or placebo).)
- Change in total Oral Morphine Equivalents Consumption of the Previous Week(Baseline (before the first LK or placebo infusion), before the second infusion (LK or placebo), and, one week after the second infusion (LK or placebo).)
- Immediate Analgesic Effect of the Infusion (LK or placebo)(Before the infusion and one hour after infusion termination.)
- Change in the Score of the Beck Depression Inventory(Baseline (immediately before the first LK or placebo infusion) and one week after the second infusion.)
- Rating of Overall Improvement Using Patient Global Impression of Change Scale(one week after the second (LK or placebo) infusion)
研究者
Konstantinos Kalimeris
Associate Professor of Anesthesiology
National and Kapodistrian University of Athens