Evaluation of the Efficacy of a Single Infusion of Ketamine Combined With Magnesium Sulfate to Treat Refractory Chronic Cluster Headache
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 93
- 试验地点
- 28
- 主要终点
- Change in weekly attacks between day 7 - day 13 period compared to the pre-treatment period
研究概览
简要总结
Chronic cluster headache (CCH) is a rare primary headache disorder, defined by episodic attacks that occur for more than one year with no remission period or with remission periods lasting < 3 months (ICHD-3 criteria). In certain cases, CCH patients become drug-resistant and continue to suffer almost daily attacks.
Ketamine appears to be effective in a variety of chronic pain conditions, such as refractory headache, and can show an enhanced analgesic effect when combined with magnesium. A single infusion of ketamine-magnesium combination has been described to reduce attacks in 17 patients with rCCH. The main outcome was a comparison of the number of daily attacks two weeks prior to the infusion and one week after (days 7-8). The number of daily attacks decreased from 4.3±2.4 before treatment to 1.3±1.0 after treatment (p<0.001). 13/17 had at least 50% response. Thus, the goal of this placebo-controlled study is to try to confirm these findings.
详细描述
Chronic cluster headache (CCH) is a rare primary headache disorder, defined by episodic attacks that occur for more than one year with no remission period or with remission periods lasting < 3 months (ICHD-3 criteria). In certain cases, CCH patients become drug-resistant and continue to suffer almost daily attacks.
Ketamine appears to be effective in a variety of chronic pain conditions, such as refractory headache, and can show an enhanced analgesic effect when combined with magnesium. A single infusion of ketamine-magnesium combination has been described to reduce attacks in 17 patients with rCCH. The main outcome was a comparison of the number of daily attacks two weeks prior to the infusion and one week after (days 7-8). The number of daily attacks decreased from 4.3±2.4 before treatment to 1.3±1.0 after treatment (p<0.001). 13/17 had at least 50% response. Thus, the goal of this placebo-controlled study is to try to confirm these findings.
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
- Double (Participant, Investigator)
盲法说明
infusion will be prepared by a nurse that is not blinded to the treatment and will not take part to patient evaluation. Active and control treatments are of transparent colour and will not be recognisable.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >= 18 years
- •Chronic cluster headache diagnosis made according to ICHD-3 criteria
- •A mean of at least 2 attacks/day during the 14 days before infusion
- •Insufficient efficacy or intolerance or contra-indication to the use of the 3 main validated treatments (verapamil, lithium and sub-occipital steroids injections)
- •Stable preventive treatment for at least 7 days before infusion
排除标准
- •Pregnant or lactating woman
- •Contra-indication to ketamine use (uncontrolled high blood pressure, stoke history, severe cardiac failure)
- •Ketamine use during the previous year
- •Hypersensitivity to the product or their metabolites
- •Severe renal insufficiency (creatinine clearance < 30ml/min)
研究组 & 干预措施
Ketamine + Magnesium
patients in the experimental group will receive 0.5mg/kg of ketamine over 2 hours, diluted in 50cc of NaCl 0.9% and 3g of magnesium sulfate over 30 minutes diluted in 250cc of NaCl 0.9%.
干预措施: Ketamine + Magnesium sulfate (drug combination) (Drug)
Control
patients in the control group will receive 25mg of hydroxyzine over 2 hours, diluted in 50cc of NaCl 0.9% and 250cc of NaCl 0.9% over 30 minutes
干预措施: Ketamine + Magnesium sulfate (drug combination) (Drug)
结局指标
主要结局
Change in weekly attacks between day 7 - day 13 period compared to the pre-treatment period
时间窗: pre-treatment period and day 7-day 13 post-treatment period
Evaluate the efficacy of a single infusion of ketamine combined with magnesium sulfate compared to a control group receiving hydroxyzine (active placebo) in terms of weekly attacks between day 7 and day 13 period and pre-treatment period
次要结局
- Proportion of 30% responders(day 7 to day 90)
- Proportion of 50% responders(day 7 to day 90)
- Proportion of 75% responders(day 7 to day 90)
- week by week attacks frequency(day 0 to day 90)
- patient global impression of change (PGIC)(Day 90)
- Infusion's safety(day 1)
- Proportion of patients necessitating rescue therapy(Day 15)
- Treatment response according to initial magnesemia(day 8)
- Attacks treatment consumption(day 0 to day 90)
- Direct medical cost(day 0 to day 90)
- Anxiety evolution(Day 90)
- depression evolution(Day 90)
- Change in weekly attacks between day 14 - day 20 period compared to the pre-treatment period(pre-treatment period and day 14 - day 20 post-treatment period)
- Change in weekly attacks between day 21 - day 27 period compared to the pre-treatment period(pre-treatment period and day 21 - day 27 post-treatment period)
- Change in weekly attacks between day 28 - day 34 period compared to the pre-treatment period(pre-treatment period and day 28 - day 34 post-treatment period)
- Adverse events assessment(D0 to D90)
- assessment of blind quality(Day 0)
- Treatment response according to initial magnesemia(day 8)
- Attacks treatment consumption(day 0 to day 90)
- Direct medical cost(day 0 to day 90)
- Anxiety evolution(Day 90)
- depression evolution(Day 90)
- Proportion of 30% responders(day 7 to day 90)
- Proportion of 50% responders(day 7 to day 90)
- patient global impression of change (PGIC)(Day 90)
- Infusion's safety(day 1)