Ketamine for Acute Migraine in the Emergency Department

A Randomized Placebo-Controlled Trial of Sub-Dissociative Ketamine for Treatment of Acute Migraine-Type Headache in the Emergency Department

This research study will be a prospective, randomized, double-blind, placebo-controlled trial. Because ketamine has yet to be directly studied as treatment for acute migraine headache in the emergency department, the research team is initially interested if ketamine can reduce pain scores in headache patients and reduce the incidence of recurrence while exhibiting an adequate safety profile. By using a placebo-controlled study design, the research team can adequately investigate the effectiveness of the medication in a subgroup previously not well studied.

Study Overview

• Status: Completed
• Conditions: Headache
• Intervention / Treatment: Drug: Normal Saline; Drug: Ketamine

Detailed Description

The investigators propose enrollment of patients upon or shortly after presentation to the emergency department for treatment with ketamine or placebo. 30 minutes after study drug is administered, patients will have the option to request rescue medication which will be ordered by the treating physician according to standard emergency department protocol. Pain scores will be documented using the Numerical rating scale (NRS-11), 4-Point Pain Intensity Categorical Scale, and 4-Point Functional Disability Scale at 0 minutes, 30 minutes, and 60 minutes post treatment. Follow-up telephone calls will be made 72-120 hours after treatment to assess the incidence of recurrence of head pain and patient satisfaction with the treatment.

Subjects eligible for this study must present to the emergency department with a chief complaint of primary headache that is determined non-emergent by the treating physician.

Upon block randomization, each subject will receive an intravenous dose of 0.2 mg/kg, with a maximum dose of 30mg, of ketamine or an equivalent volume of saline. After 30 minutes patients will be asked if they need rescue medication, and the treating physician will administer rescue treatment, if requested.

The research hypotheses include:

1. The proportion of patients achieving significant pain reduction at 30 minutes will be higher in the ketamine treatment group compared to the placebo group.
2. The proportion of patients experiencing pain response, defined as <50% reduction in the visual analog score compare to the baseline and a reduction of the 4-Point Pain Intensity Categorical Scale to a 1 or 0, will be higher for patients receiving ketamine compared to those receiving the placebo.
3. Patients treated with ketamine for headache will experience lower recurrence rates within 24 hours
4. Ketamine will demonstrate an adequate safety profile.

The last two questions will be exploratory and not included in the power analysis.

It is expected that ketamine will demonstrate a satisfactory safety profile with limited side effects. The proportion of patients attaining pain response is expected to be higher in the ketamine treatment group compared to placebo. It is also expected that patients treated with ketamine alone will be less likely to experience a recurring headache within 72 hours of treatment than those treated with placebo and rescue medication.

The primary outcome will be achievement of pain response at 30 minutes after ketamine dose. Achievement of pain response will be defined as reduction in baseline pain score by at least 50% on the NRS scale. Secondary outcomes will include attainment of pain-free state, patient headache relief, recurrence of headache, recovery of functional disability, and need for rescue medication.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Carilion Roanoke Memorial Emergency Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-65 years of age
• Chief complaint of headache
• International Classification of Headache Disorder classification of migraine or probable migraine with or without aura
• Has decision making capacity
• Consent
• Provider determination of non-emergent cause

Exclusion Criteria:

• Over the age of 50 with first time headache
• Known adverse reaction or tolerance to study medication
• Headache due to trauma
• New onset, focal, abnormal, neurologic findings
• New onset seizures
• History of metastatic cancer or neoplasm
• Active psychotic symptoms
• Altered mental status
• Provider intends to preform lumbar puncture
• Pregnancy
• Breast feeding
• Previous enrollment in study
• Fever > 100.3 F
• Physiologic instability (blood pressure < 90/50 or >170/100, heart rate <50 or >120, chronic respiratory, renal or hepatic failure)
• Suspected cardiac pain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Control; Patients will receive an equivalent volume of normal saline intravenously.	Drug: Normal Saline; Patients will receive normal saline intravenously, pain scores will be collected after 30 minutes. At that time rescue medication will also be offered. Pain scores will continued to be recorded until 60 minutes have passed since drug administration.
Experimental: Ketamine; Patients will receive 0.2mg/kg ketamine intravenously over one minute.	Drug: Ketamine; Patients in this arm will receive 0.2mg/kg ketamine intravenously, pain scores will be collected after 30 minutes. At that time rescue medication will also be offered. Pain scores will continued to be recorded until 60 minutes have passed since drug administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of Pain Response After Ketamine Dose.	NRS (National rating scale) pain score change from baseline following ketamine dose. Minimum score is 0, maximum score is 10, and higher scores mean worse pain.	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Categorical Pain Score Change From Baseline	change in baseline categorical pain score at 30 minutes (categorical pain intensity score from 0 to 3 where 0="no headache" and 3="severe headache")	30 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Disability Score Change From Baseline	change in functional disability from baseline at 30 minutes (functional disability score from 0 to 3 where 0="no disruption of daily activities" and 3="performance of daily activities is severely impaired")	30 minutes

Collaborators and Investigators

• Sponsor: Carilion Clinic
• Collaborators: Virginia Polytechnic Institute and State University
• Investigators: Principal Investigator: Corey Corey, MD, Carilion Clinic

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: February 24, 2016
• First Submitted That Met QC Criteria: February 26, 2016
• First Posted (Estimate): March 3, 2016

Study Record Updates

• Last Update Posted (Actual): March 26, 2021
• Last Update Submitted That Met QC Criteria: March 2, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Ketamine; Migraine; Headache; Emergency Department
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Disease Attributes; Headache Disorders, Primary; Headache Disorders; Emergencies; Migraine Disorders; Headache; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 1921

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No