Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05967442 |
| Other study ID # |
AHC-7192-D5000322 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
August 23, 2019 |
| Est. completion date |
April 6, 2023 |
Study information
| Verified date |
July 2023 |
| Source |
Advocate Health Care |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This investigation describes a proposed clinical trial that will evaluate the relative
efficacy of intravenous magnesium sulfate for the treatment of migraine compared to
intravenous metoclopramide (Reglan) and intravenous prochlorperazine (Compazine) in the
treatment of acute headache and migraine in adult patients. The ultimate objective will be
clinical application of these drugs in the emergency department for the treatment of acute
headache and migraine.
The two phenothiazines (metoclopramide and prochlorperazine) have been routinely utilized in
the treatment of acute headache and migraine in the emergency department setting. Per the
2017 American Headache Society guidelines, both intravenous metoclopramide and intravenous
procholorperazine are recommended as "clinicians should offer" agents with level B evidence.
Of note, there are no agents with level A evidence purported by this guideline for acute
management of migraine. The same guideline offers "no recommendation can be made regarding
the role of intravenous magnesium for adults who present to the ED with acute migraine.
However intravenous magnesium may be of benefit to patients who present with migraine with
aura." Multiple trials have evaluated intravenous magnesium's safety and efficacy in the
management of acute migraine. These have demonstrated the tolerability of intravenous
magnesium on a with breadth of patients. Most commonly the primary adverse event was flushing
which self-resolved. No cases of hypotension were reported.
None of these study agents have been withdrawn from the market.
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.
