Efficacy of Haloperidol vs. Metoclopramide for Treatment of Acute Headaches and Migraines in the Emergency Department

• Sponsor: OhioHealth (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02972502
• Collaborator: (none)
• Enrollment: 66
• Location: 1
• Arms: 2
• Duration (Months): 38.7
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

Metoclopramide (Reglan) is a common agent used for relief of headaches in the emergency department (ED).In this study the investigators seek to explore another option for treatment of headaches in the ED, one that may be more efficacious and efficient. Haloperidol (Haldol), a butyrophenone class of medication, is thought to act by affecting the dopamine 2 receptor in the brain.

By exploring haloperidol as an option for treatment, the investigators hope to discover a more efficient and effective medication for the treatment of non-traumatic headaches, thereby decreasing a patient's length of stay in the department and decreasing the rate of return visits for continued discomfort from the same headache. This study could lead to the increased usage of haloperidol as a first line agent in the treatment of prolonged headaches presenting to the ED.

Condition or Disease	Intervention/Treatment	Phase
Headache, Migraine	Drug: Metoclopramide; Drug: Haloperidol; Other: Normal Saline; Drug: Diphenhydramine	Phase 4

Detailed Description

At this time, choice of medications for the treatment of headaches in the ED is still based on personal and patient preferences because no properly constructed trials have been carried out that would allow identification of a superior agent. Metoclopramide (Reglan) is a common agent used for relief of headaches in the ED. Uncontrolled studies have shown successful relief of migraine with metoclopramide of 75%. Further studies have reported success rate of 67% with IV metoclopramide. In this study the investigators seek to explore another option for treatment of headaches in the ED, one that may be more efficacious and efficient. Haloperidol (Haldol), a butyrophenone class of medication, is thought to act by affecting the dopamine 2 receptor in the brain. These receptors are relatively abundant in the brainstem nuclei and sympathetic ganglia and nerves, through which they may regulate autonomic visceral, gastrointestinal, and hemodynamic responses frequently associated with migraine. One study, demonstrated that 4 out of 5 patients felt significant relief in pain intensity with the use of haloperidol, even when other medications had failed. Relapses were rare, and several patients reported that haloperidol interrupted the prolonged, intractable migraine spiral they had suffered for days. Furthermore, a case series of six cases of migraine treated with 5mg of haloperidol IV after a 500 to 1000ml bolus of IV fluids reported complete or substantial relief within 25 to 65 minutes and side effects were reported as minimal.

The investigators hypothesize that Haloperidol is more efficacious than metoclopramide in the treatment of an acute headache or migraine in the ED in regard to a self-reported pain rating scale (Numeric Pain Intensity Scale), need for additional medication, emergency department return rates, and resolution of symptoms.

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Investigating the Efficacy of Using Haloperidol vs. Metoclopramide for Treatment of Acute Headaches and Migraines in the Emergency Department: A Prospective Randomized Clinical Trial
• Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Apr 24, 2017
• Actual Study Completion Date: Apr 24, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Metoclopramide (Reglan) Patients will receive 10 mg of intravenous (IV) metoclopramide following a 1-liter bolus of normal saline (NS) and 25 mg of IV diphenhydramine.	Drug: Metoclopramide; Patients receive 10 mg of intravenous (IV) metoclopramide.; Other Names: Reglan ; Other: Normal Saline; All patients receive a 1-liter bolus of normal saline (NS); Drug: Diphenhydramine; All patients receive 25 mg of intravenous (IV) diphenhydramine.; Other Names: Benadryl
Experimental: Haloperidol (Haldol) Patients will receive 2.5 mg of intravenous (IV) haloperidol following a 1-liter bolus of normal saline (NS) and 25 mg of IV diphenhydramine.	Drug: Haloperidol; Patients receive 2.5 mg of IV haloperidol.; Other Names: Haldol ; Other: Normal Saline; All patients receive a 1-liter bolus of normal saline (NS); Drug: Diphenhydramine; All patients receive 25 mg of intravenous (IV) diphenhydramine.; Other Names: Benadryl

Outcome Measures

Primary Outcome Measures

1. Change in Pain Score According to the Numeric Pain Intensity Scale [Change from baseline (prior to treatment) to 1 hour post treatment (1 hour)]

   Numeric Pain Intensity scale is a standard rating tool for pain, ranging from 0-10, with 0=no pain and 10=worst pain imaginable.

Secondary Outcome Measures

1. Need for Additional Medications Used in the Emergency Department (ED) [48 hours post discharge]

   Need for additional medications in the ED will be evaluated via chart review at 48 hours post discharge

2. Occurrence of Patient Return to the Emergency Department (ED) or Other Healthcare Provider for Headache/Migraine Within 48 Hours of ED Discharge [48 hours post discharge]

   Occurrence of patient return to the ED or other healthcare provider for headache/migraine within 48 hours of ED discharge will be evaluated via chart review at 48 hours post discharge

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients who present with a headache or migraine with onset less than or equal to 72 hours

Exclusion Criteria:

• Known pregnancy

• Breast-feeding women

• Known history of arrhythmias or QT prolongation (450 ms)

• Known adverse effects to haloperidol, diphenhydramine (Benadryl) or metoclopramide

• Subarachnoid hemorrhage

• Headaches caused by trauma, meningitis

• Congestive heart failure

• Parkinson's Disease

• Dementia

• Pheochromocytoma

• History of glaucoma

• History of seizures

• Non-English speaking patients

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	OhioHealth Doctors Hospital	Columbus	Ohio	United States	43228

Sponsors and Collaborators

• OhioHealth

Investigators

• Principal Investigator: Christopher Lloyd, D.O., Attending Physician

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 16, 2016

More Information

Publications

None provided.

• Responsible Party: Christopher Lloyd, Attending Physician, OhioHealth
• ClinicalTrials.gov Identifier: NCT02972502
• Other Study ID Numbers: 13-0078
• First Posted: Nov 23, 2016
• Last Update Posted: Oct 23, 2018
• Last Verified: Sep 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Christopher Lloyd, Attending Physician, OhioHealth: Metoclopramide (Reglan); Haloperidol (Haldol)
• Additional relevant MeSH terms: Migraine Disorders; Emergencies; Headache; Diphenhydramine; Promethazine; Haloperidol; Metoclopramide; Haloperidol decanoate

Study Results

Participant Flow

Arm/Group Title	Metoclopramide (Reglan)	Haloperidol (Haldol)
Arm/Group Description	Patients will receive 10 mg of intravenous (IV) metoclopramide following a 1-liter bolus of normal saline (NS) and 25 mg of IV diphenhydramine. Metoclopramide: Patients receive 10 mg of intravenous (IV) metoclopramide. Normal Saline: All patients receive a 1-liter bolus of normal saline (NS) Diphenhydramine: All patients receive 25 mg of intravenous (IV) diphenhydramine.	Patients will receive 2.5 mg of intravenous (IV) haloperidol following a 1-liter bolus of normal saline (NS) and 25 mg of IV diphenhydramine. Haloperidol: Patients receive 2.5 mg of IV haloperidol. Normal Saline: All patients receive a 1-liter bolus of normal saline (NS) Diphenhydramine: All patients receive 25 mg of intravenous (IV) diphenhydramine.
Period Title: Overall Study
STARTED	35	31
COMPLETED	31	29
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	Metoclopramide (Reglan)	Haloperidol (Haldol)	Total
Arm/Group Description	Patients will receive 10 mg of intravenous (IV) metoclopramide following a 1-liter bolus of normal saline (NS) and 25 mg of IV diphenhydramine. Metoclopramide: Patients receive 10 mg of intravenous (IV) metoclopramide. Normal Saline: All patients receive a 1-liter bolus of normal saline (NS) Diphenhydramine: All patients receive 25 mg of intravenous (IV) diphenhydramine.	Patients will receive 2.5 mg of intravenous (IV) haloperidol following a 1-liter bolus of normal saline (NS) and 25 mg of IV diphenhydramine. Haloperidol: Patients receive 2.5 mg of IV haloperidol. Normal Saline: All patients receive a 1-liter bolus of normal saline (NS) Diphenhydramine: All patients receive 25 mg of intravenous (IV) diphenhydramine.	Total of all reporting groups
Overall Participants	31	29	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.5 (9.9)	36.9 (10.0)	35.7 (10.0)
Sex: Female, Male (Count of Participants)
Female	8 25.8%	9 31%	17 28.3%
Male	18 58.1%	14 48.3%	32 53.3%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	18 58.1%	19 65.5%	37 61.7%
African American	6 19.4%	4 13.8%	10 16.7%
Somali	1 3.2%	0 0%	1 1.7%
Hispanic	1 3.2%	0 0%	1 1.7%
Region of Enrollment (participants) [Number]
United States	31 100%	29 100%	60 100%
Baseline Pain Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	8.13 (1.36)	8.54 (1.34)	8.35 (1.38)

Outcome Measures

1. Primary Outcome

Title	Change in Pain Score According to the Numeric Pain Intensity Scale
Description	Numeric Pain Intensity scale is a standard rating tool for pain, ranging from 0-10, with 0=no pain and 10=worst pain imaginable.
Time Frame	Change from baseline (prior to treatment) to 1 hour post treatment (1 hour)

Outcome Measure Data

Analysis Population Description

Study was terminated early. Information entered for n=49 participants. Data not collected for 11 participants.

Arm/Group Title	Metoclopramide (Reglan)	Haloperidol (Haldol)
Arm/Group Description	Patients will receive 10 mg of intravenous (IV) metoclopramide following a 1-liter bolus of normal saline (NS) and 25 mg of IV diphenhydramine. Metoclopramide: Patients receive 10 mg of intravenous (IV) metoclopramide. Normal Saline: All patients receive a 1-liter bolus of normal saline (NS) Diphenhydramine: All patients receive 25 mg of intravenous (IV) diphenhydramine.	Patients will receive 2.5 mg of intravenous (IV) haloperidol following a 1-liter bolus of normal saline (NS) and 25 mg of IV diphenhydramine. Haloperidol: Patients receive 2.5 mg of IV haloperidol. Normal Saline: All patients receive a 1-liter bolus of normal saline (NS) Diphenhydramine: All patients receive 25 mg of intravenous (IV) diphenhydramine.
Measure Participants	26	23
Mean (Standard Deviation) [units on a scale]	-2.86 (2.37)	-5.13 (2.59)

2. Secondary Outcome

Title	Need for Additional Medications Used in the Emergency Department (ED)
Description	Need for additional medications in the ED will be evaluated via chart review at 48 hours post discharge
Time Frame	48 hours post discharge

Outcome Measure Data

Analysis Population Description

Study was terminated early. Information entered for n=49 participants. Data not collected for 11 participants.

Arm/Group Title	Metoclopramide (Reglan)	Haloperidol (Haldol)
Arm/Group Description	Patients will receive 10 mg of intravenous (IV) metoclopramide following a 1-liter bolus of normal saline (NS) and 25 mg of IV diphenhydramine. Metoclopramide: Patients receive 10 mg of intravenous (IV) metoclopramide. Normal Saline: All patients receive a 1-liter bolus of normal saline (NS) Diphenhydramine: All patients receive 25 mg of intravenous (IV) diphenhydramine.	Patients will receive 2.5 mg of intravenous (IV) haloperidol following a 1-liter bolus of normal saline (NS) and 25 mg of IV diphenhydramine. Haloperidol: Patients receive 2.5 mg of IV haloperidol. Normal Saline: All patients receive a 1-liter bolus of normal saline (NS) Diphenhydramine: All patients receive 25 mg of intravenous (IV) diphenhydramine.
Measure Participants	26	23
Yes	7 22.6%	4 13.8%
No	4 12.9%	9 31%
Unknown	15 48.4%	10 34.5%

3. Secondary Outcome

Title	Occurrence of Patient Return to the Emergency Department (ED) or Other Healthcare Provider for Headache/Migraine Within 48 Hours of ED Discharge
Description	Occurrence of patient return to the ED or other healthcare provider for headache/migraine within 48 hours of ED discharge will be evaluated via chart review at 48 hours post discharge
Time Frame	48 hours post discharge

Outcome Measure Data

Analysis Population Description

Study was terminated early. Information entered for n=49 participants. Data not collected for 11 participants.

Arm/Group Title	Metoclopramide (Reglan)	Haloperidol (Haldol)
Arm/Group Description	Patients will receive 10 mg of intravenous (IV) metoclopramide following a 1-liter bolus of normal saline (NS) and 25 mg of IV diphenhydramine. Metoclopramide: Patients receive 10 mg of intravenous (IV) metoclopramide. Normal Saline: All patients receive a 1-liter bolus of normal saline (NS) Diphenhydramine: All patients receive 25 mg of intravenous (IV) diphenhydramine.	Patients will receive 2.5 mg of intravenous (IV) haloperidol following a 1-liter bolus of normal saline (NS) and 25 mg of IV diphenhydramine. Haloperidol: Patients receive 2.5 mg of IV haloperidol. Normal Saline: All patients receive a 1-liter bolus of normal saline (NS) Diphenhydramine: All patients receive 25 mg of intravenous (IV) diphenhydramine.
Measure Participants	26	23
Yes	0 0%	0 0%
No	26 83.9%	23 79.3%

Adverse Events

Time Frame	48 hours
Adverse Event Reporting Description	Study was terminated early. Some information entered for n=49 participants. Data not collected for 11 participants.
Arm/Group Title	Metoclopramide (Reglan)		Haloperidol (Haldol)
Arm/Group Description	Patients will receive 10 mg of intravenous (IV) metoclopramide following a 1-liter bolus of normal saline (NS) and 25 mg of IV diphenhydramine. Metoclopramide: Patients receive 10 mg of intravenous (IV) metoclopramide. Normal Saline: All patients receive a 1-liter bolus of normal saline (NS) Diphenhydramine: All patients receive 25 mg of intravenous (IV) diphenhydramine.		Patients will receive 2.5 mg of intravenous (IV) haloperidol following a 1-liter bolus of normal saline (NS) and 25 mg of IV diphenhydramine. Haloperidol: Patients receive 2.5 mg of IV haloperidol. Normal Saline: All patients receive a 1-liter bolus of normal saline (NS) Diphenhydramine: All patients receive 25 mg of intravenous (IV) diphenhydramine.
All Cause Mortality
	Metoclopramide (Reglan)		Haloperidol (Haldol)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/23 (0%)
Serious Adverse Events
	Metoclopramide (Reglan)		Haloperidol (Haldol)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Metoclopramide (Reglan)		Haloperidol (Haldol)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/23 (0%)

Limitations/Caveats

This study was terminated by the IRB due to PI lapse in required training. Outcomes data reported includes preliminary figures for n=49 patients. Data not collected from 11 patients.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.