Study Description

Migraine or severe headache affected one-fifth of women and one-tenth of men in 2015 and is one of the leading causes of disability in the world. Over one million visits to emergency departments (ED) in the US are due to migraines. Migraine, previously believed to be a vascular disorder, is caused by inflammation due to vasodilation in the meninges secondary to the release of vasoactive neuropeptides by stimulation of the trigeminal nerve. This inflammation can result in symptoms such as headache, nausea, vomiting, dizziness, photophobia and phonophobia.

Despite migraine being a common disorder, there has yet to be a cure. Several classes of medications have been studied for the treatment of migraine. Recently, conventional therapy has shifted to the use of antidopaminergics including prochlorperazine, metoclopramide and haloperidol, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen, and triptans, sumatriptan being the most commonly utilized. 5Although intravenous opioids have historically been the most common treatment for migraines, their use has fallen out of favor due to their association with increased recurrence of headaches and ED visits, abuse potential, and most recently severe intravenous opiate shortage. Alternative treatments include ketamine, propofol, dihydroergotamine and magnesium.

Magnesium is an intracellular cation that has been associated with both the function of serotonin and regulation of vascular tone, which are both mechanisms that implicate its role in the treatment of migraine. Intravenous magnesium sulfate has been studied as a treatment for migraine compared to placebo, metoclopramide and prochlorperazine. These studies have shown that magnesium is well-tolerated with a good safety profile and may be efficacious in the treatment of migraine. Metoclopramide, prochlorperazine and magnesium have been recommended in clinical practice guidelines and have become routine standard of care for treatment of migraine in this emergency department. However, no trial has evaluated these modalities simultaneously in the same population. The purpose of our study is to compare the relative efficacy for magnesium, metoclopramide, and prochlorperazine in the treatment of headache and migraine.

Patients presenting to Advocate Christ Medical Center emergency department with a diagnosis of migraine or headache from October 1, 2018 to April 1, 2020 seven days a week from 6am to 1:30am. The emergency department physician will identify patients eligible for the study and alert the emergency medicine pharmacist who will consent the patient using the HRP-502 Form (attached). Each patient will be handed a copy of the consent form and signed consent forms will be kept at Advocate Christ Medical Center in the pharmacy resident's locked office.

Via monthly block randomization, patients will be given one of three guideline recommended study drugs. Allocation will be concealed by a pharmacist (not participating in the rest of the study) solely designated to choose which drug will be the assigned study drug for each month. The pharmacists, physicians, and nurses participating in administration of the medications will be blinded to which drug is being administered during each month. Metoclopramide, prochlorperazine and magnesium have been recommended in clinical practice guidelines and have become routine standard of care for treatment of migraine in this emergency department. All three study drugs will be stored in the investigational medication refrigerator located in the main pharmacy. A pharmacist on duty in the emergency department will obtain the medication from the refrigerator and deliver it to the bedside nurse who is actively caring for the patient after an order from the physician.

Magnesium 2gm/50mL D5W will be administered as an intravenous bolus over 20 minutes. Prochlorperazine 10mg/50mL D5W will be administered as an intravenous bolus over 20 minutes. Metoclopramide 10mg/50mL D5W will be administered as an intravenous bolus over 20 minutes.

The primary outcome of this study will be mean change in pain from baseline to 30 minutes after initiation of infusion (as defined on a 11-point Numeric Rating Scale. Secondary endpoints include mean change in pain from baseline to 60 minutes and 120 minutes after initiation of infusion (as defined on a 11-point Numeric Rating Scale), time to emergency department discharge, and adverse effects due to administration of study drug (hypotension, flushing, akathisia, dystonia, nausea, vomiting, dizziness, drowsiness, other self-reported adverse effects).

The following data points will be collected: financial identification number (FIN), age, gender, race, weight, height, initial vitals (heart rate, blood pressure, respiratory rate, temperature, and oxygen saturation), past medical history, medications taken prior to arrival, hospital length of stay, rescue medications given for extrapyramidal side effects or pain due to treatment failure (including dose, route and time to administration of rescue medication).

All data will be collected without patient identifiers and confidentiality will be maintained. Furthermore, information will be kept on a password protected computer located at Advocate Christ Medical Center in the pharmacy resident's locked office. The recorded data will be destroyed following completion of study and analysis of data.

The following study variables will be collected based on the study objectives:

FIN (for identification of patients in Care Connection only)

Age

Gender

Race

Weight

Height

Initial vitals (heart rate, blood pressure, respiratory rate, temperature and oxygen saturation)

Past Medical History

Antimigraine medications taken prior to arrival (i.e: acetaminophen, NSAIDs, opiates, triptans, Fioricet, ergots, metoclopramide, magnesium, prochlorperazine, antimuscarinics, propranolol)

Hospital length of stay

Rescue medications given for treatment failure (i.e: acetaminophen, NSAIDs, opiates, triptans, Fioricet, ergots, metoclopramide, magnesium, prochlorperazine, antimuscarinics, propranolol) or for extrapyramidal side effects (diphenhydramine or benztropine)

Dose and route of rescue medications given

Time to administration of rescue medication

All data will be collected without patient identifiers and confidentiality will be maintained. Furthermore, information will be kept on a password protected computer located at Advocate Christ Medical Center in the pharmacy resident's locked office. The recorded data will be destroyed following completion of study and analysis of data. Data collection and analysis will only be conducted by the members of the research team. If data is needed to transported, it will only be done by the research team and will only be transported between team members. Transfer of data will be done person to person or electronically via a password protected drive.

All information gathered during this study will be kept confidential. Study data will be managed using REDCap16 electronic data capture tools hosted by Advocate Health Care. REDCap (Research Electronic Data Capture) is a secure, web-based application designed to support data capture for research studies, providing 1) an intuitive interface for validated data entry; 2) audit trails for tracking data manipulation and export procedures; 3) automated export procedures for seamless data downloads to common statistical packages; and 4) procedures for importing data from external sources. The data will be accessible to only the study investigators and REDCap administrators. Subjects will be assigned case numbers. Data being extracted from the REDCap database will include only the case numbers and be de-identified via the electronic removal of PHI prior to data download. After data collection is complete and records have been verified, identifiers will be permanently removed from the data set. Any study documentation including regulatory information, consent forms, and data collection forms will be secured in a locked cabinet in the pharmacy resident's locked office and will be destroyed upon completion of the study and analysis of the data.

A maximum of 264 subjects (88 subjects treated with magnesium, 88 subjects treated with metoclopramide, and 88 subjects treated with prochlorperazine) will be included in this prospective randomized study based on estimates of patients presenting to the Emergency Department with a primary diagnosis of headache or migraine at Advocate Christ Medical Center from past years. With this sample size, a 80% power to detect a mean difference of 1.4 points between groups for the primary outcome of mean Numeric Rating Scale with an alpha of 0.05.

Descriptive statistics will be calculated for all variables and presented overall and by group using mean ± SD for continuous variables and count/percentages for categorical variables. Comparisons will be made between groups for all outcomes using Chi-Square or Fisher's exact tests as necessary for categorical data and a one-way ANOVA as appropriate for all continuous data. All tests will be two-tailed and a p-value of 0.05 will be considered statistically significant in all analyses. Also to be discussed assess utilizing multiple predictive multivariate logistic regression models.

Condition or Disease	Intervention/Treatment
Migraine Headache	Drug: Magnesium Sulfate Drug: Metoclopramide 10mg Drug: Prochlorperazine (Compazine) Injection

Study Design

Study Type	Interventional
Actual Enrollment	288 participants
Design Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Quadruple
Primary Purpose	Treatment
Official Title	A Randomized, Placebo-Controlled, Double-Blind Study of the Effects of Magnesium Compared to Conventional Therapy on Acute Migraine
Study Start Date	August 23, 2019
Actual Primary Completion Date	March 31, 2020
Actual Study Completion Date	April 6, 2023

Groups and Cohorts

Group/ Cohort	Intervention/ Treatment
Magnesium	Drug: Magnesium Sulfate Magnesium Sulfate 2gm in 50ml D5W over 20 minutes
Metoclopramide Metoclopramide 10mg in 50ml D5W over 20 minutes	Drug: Metoclopramide 10mg
Prochlorperazine Prochlorperazine in 50ml D5W over 20 minutes	Drug: Prochlorperazine (Compazine) Injection

Outcome Measures

Primary Outcome Measures

1. 30min pain score [30 minutes after initiation]
   11 point Numerical Rating Scale pain score at 30 minutes after initiation of drug

Secondary Outcome Measures

1. LOS [Upon discharge]
   Emergency Department Length of stay. Measured from time of arrival to time of discharged documented in the electronic medical record. Duration measured in minutes

Eligibility Criteria

Ages Eligible for Study	18 Years and Older (Adult, Older Adult)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	Yes
Inclusion Criteria	Age > 18 years or older Able to provide informed consent Primary diagnosis of headache or migraine Between October 1, 2018 to April 1, 2020 Presenting to Advocate Christ Medical Center emergency department and meet clinical assessment per physician
Exclusion Criteria	Pregnancy defined as a positive urine HCG Stated history of renal impairment Allergy or sensitivity to any study drugs Concomitant treatment at the time of study drug administered in the emergency department Patients with a history of this study participation

Contacts and Locations

Sponsors and Collaborators	Advocate Health Care
Locations	Advocate Christ Medical Center | Oak Lawn, Illinois, United States, 60453

More Information

Additional Relevant MeSH Terms

• Migraine Disorders
• Headache
• Headache Disorders, Primary
• Headache Disorders
• Brain Diseases
• Central Nervous System Diseases
• Nervous System Diseases
• Pain
• Neurologic Manifestations