A Multi-center Randomized Controlled Trial of Efficacy and Safety of Intravenous Ketamine for Chronic Daily Headaches: The KetHead Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 56
- 试验地点
- 4
- 主要终点
- Difference in headache days between the 2 groups
研究概览
简要总结
Chronic daily headaches (CDH) poses a significant burden on patients, healthcare systems and the society. Intravenous (IV) ketamine infusion, an intervention that is widely available and scalable, can treat CDH by reversing receptor-mediated sensitization. This study is a multicenter, placebo-controlled, parallel group randomized trial with blinding of participants and observers with the goal of comprehensively assessing the effect of high-dose IV ketamine infusion (1 mg.kg-1.h-1 for six hours) on the frequency and intensity of headaches, mood, activity, sleep, quality of life and safety of ketamine for three months after the interventions. Use of validated questionnaires, wearable technology, a research team that includes investigators with expertise in studying ketamine and in evaluating treatments for CDH and pain syndromes are some of the unique features of this project.
Our study aims to prospectively assess the efficacy and safety of high-dose intravenous ketamine infusions compared to saline infusions in participants with CDH syndrome.
详细描述
The KetHead study is designed as a multi-center, placebo-controlled, superiority randomized controlled trial with two parallel groups and blinding of participants and outcome assessors. It will be conducted at two chronic pain centers, Toronto Western Hospital and Sinai Health System. Eligible patients will be identified and enrolled in the pain clinics. Randomization will take place upon patient enrollment. Treating physicians, patients, close contacts, study coordinators and primary outcome assessors will be blinded to treatment allocation.
Interventions common to both arms Participating patients will receive the infusion at the pain infusion unit at Toronto Western Hospital, under hemodynamic monitoring, supervised by an Anesthesiologist. At the start of the infusion, all patients will receive IV midazolam 0.04 mg.kg-1 (maximum 3 mg) and subsequently 0.01-0.02 mg.kg-1 every hour to keep participants in a sedated but arousable state (Ramsay Sedation Scale score 3 or 4)22 to blind the participants and assessors to group allocation. Eight mg of ondansetron and 8 mg of dexamethasone will be administered to all participants to prevent nausea, 5000 units of heparin will be given subcutaneously to prevent thrombo-embolic events. Medications will be administered by an Anesthesiologist.
A. Intervention group: For individuals randomized to the IV Ketamine group, 1 mg.kg-1 bolus will be given. This will be prepared as a syringe of 10 cc of Ketamine 10 mg/ml. This is followed by an infusion of 1 mg.kg-1.hour-1 (ketamine diluted in saline to 2 mg/mL at 0.5 mL.kg-1.hour-1) for six hours.
B. Control group: For individuals in the saline infusion group, an IV bolus of 0.9% saline will be given. The volume will be the same as that of the ketamine bolus for that weight, to prevent unblinding of participants and assessors. This will be followed by an infusion 0.5 mL.kg-1.hour-1 of saline for six hours. The rate of the infusion will be the same as that of a ketamine infusion for that weight to prevent unblinding of participants and assessors.
Study personnel will assess patient and collect data throughout their enrollment in the study.
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, Care Provider)
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 18-75 years
- •CDH diagnosis preceding trial enrollment with headache episodes lasting for 4 or more hours occurring on 15 or more days in a month for 3 or more months (International Headache Society-IHS criteria)
- •Normal liver and kidney function tests
排除标准
- •Pregnant or breastfeeding patients
- •Pre-existing renal impairment
- •Pre-existing liver impairment
- •Chronic benzodiazepine or antipsychotic medication use
- •History of cerebrovascular event
- •Significant and untreated hypertension or severe cardiac condition
- •Hypothyroidism
- •Concomitant use of strong CYP2B6 or CYP2C8 inhibitor
- •Allergy or intolerance to ketamine
- •Pheochromocytoma
- •Any significant cognitive or language barriers that impede participation
- •CGRP antagonist use in 1 month or Onabotulinum-toxin A 3 months before infusion
- •Active diagnosis of Post-Traumatic Stress Disorder (PTSD)
- •Active diagnosis of Substance Use Disorder
- •Patients taking opioid medications with daily Oral Morphine Equivalents ≥80 mg
研究组 & 干预措施
Placebo infusion
0.9% saline infusion at the same rate as the study drug group for six hours.
干预措施: 0.9% Saline (Other)
Ketamine infusion
Intravenous Ketamine at a dose of 1 mg / kg / hour for six hours.
干预措施: Ketamine (Drug)
结局指标
主要结局
Difference in headache days between the 2 groups
时间窗: At 4 weeks
Between-group difference in the number of headache days in the first 4 weeks after the infusion. (Defined as a day in which the headache lasts 4 or more hours, or a headache of any duration for which abortive treatment (anti-inflammatories, triptans, ergot derivatives, opioids) are taken. Patients will be asked to keep track of their headache days in a diary)
次要结局
- Impact of ketamine on headache frequency after infusion(At 1 month, 2 months and 3 months)
- Impact on quality of sleep after ketamine infusion(At 1 month, 2 months and 3 months)
- Impact of ketamine infusion on patient satisfaction(At 1 month, 2 months and 3 months)
- Impact of ketamine on headache intensity after infusion(At 1 month, 2 months and 3 months)
- Impact of on emotional well being for depression after ketamine infusion(At 1 month, 2 months and 3 months)
- Impact on quality of life after ketamine infusion(At 1 month, 2 months and 3 months)
- Impact of ketamine infusion on analgesic consumption(At 1 month, 2 months and 3 months)
- Side effects after ketamine infusion(Immediately after the infusion)
- Impact on physical activity after ketamine infusion(At 1 month, 2 months and 3 months)
- Impact of on emotional well being (for catastrophizing) after ketamine infusion(At 1 month, 2 months and 3 months)
- Impact of on emotional well being for anxiety after ketamine infusion(At 1 month, 2 months and 3 months)
- Impact of ketamine on headache duration after infusion(At 1 month, 2 months and 3 months)
- Impact on sleep efficiency after ketamine infusion(At 1 month, 2 months and 3 months)
- Impact after ketamine infusion on daily activity(At 1 month, 2 months and 3 months)
- Side effects after ketamine infusion(Immediately after infusion and after 1 week)