Multi-center RCT of IV Ketamine Efficacy and Safety in Chronic Daily Headaches
A Multi-center Randomized Controlled Trial of Efficacy and Safety of Intravenous Ketamine for Chronic Daily Headaches: The KetHead Study
University Health Network, Toronto
56 participants
Jun 1, 2022
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria3
- 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
Exclusion Criteria16
- 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
- Glaucoma
- 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
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Interventions
Bolus of IV Ketamine 1 mg.kg-1 (= 0.1 ml.kg-1) followed by Infusion of Ketamine 1 mg.kg-1.hour-1 (= 0.5 mL.kg-1.hour-1) for 6 hours. 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) to blind the participants and assessors to group allocation. Ondansetron 8 mg and 8 mg of dexamethasone will be administered to prevent nausea, 5000 units of heparin will be given subcutaneously to prevent thrombo-embolic events.
Bolus of IV Saline 0.9% of 0.1 ml.kg-1 followed by Infusion of Saline 0.9% of 0.5 mL.kg-1.hour-1 for 6 hours. 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) to blind the participants and assessors to group allocation. Ondansetron 8 mg and 8 mg of dexamethasone will be administered to prevent nausea, 5000 units of heparin will be given subcutaneously to prevent thrombo-embolic events.
Locations(2)
View Full Details on ClinicalTrials.gov
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NCT05306899