Valproate Versus Ketorolac Versus Metoclopramide

• Sponsor: Montefiore Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01267864
• Collaborator: (none)
• Enrollment: 330
• Location: 1
• Arms: 3
• Duration (Months): 28
• Patients Per Site Per Month: 11.8

Study Details

Study Description

Brief Summary

This randomized study is testing 3 different intravenous medications to see which one is best for acute migraine. The three medications are metoclopramide, valproate, and ketorolac.

Condition or Disease	Intervention/Treatment	Phase
Acute Migraine	Drug: Metoclopramide; Drug: Ketorolac; Drug: Valproate	Phase 4

Detailed Description

One million patients present to US emergency departments (ED) annually for treatment of acute migraine headache. A variety of parenteral medications are used to treat acute migraine, but none offer rapid and complete headache relief without side effects. Preliminary studies have suggested that intravenous valproate, an anti-epileptic medication with established efficacy as a migraine preventive, may be useful for the treatment of acute migraine. We propose a randomized, comparative efficacy trial in which intravenous valproate is compared to two standard parenteral therapies for acute migraine. There will not be a placebo control. Included subjects will be adults 64 years and younger who meet International Headache Society criteria for acute migraine, who do not have clinical evidence of secondary (organic) headache, and who do not have allergy or contra-indication to the investigational medications. The investigational medications are 1gm of valproate, 10mg of metoclopramide, and 30mg of ketorolac. Patients will be approached for participation and randomized at the time of presentation to the ED. Pain will be assessed on an 11 point (0 to 10) verbal pain scale, validated for use in acute pain trials. Medication will be infused as a slow intravenous drip. The primary outcome will be an improvement in headache intensity one hour after initiation of the intravenous drip. Secondary outcomes include assessments of pain, functional disability, adverse events, and satisfaction with the investigational medication one, two and 24 hours after initiation of the intravenous drip. The primary analysis will use a Student's t-test for independent samples and involve three pair-wise comparisons. Using an alpha of .017 (to account for the three pairwise comparisons), a standard beta, and a validated minimum clinically significant difference on the verbal pain scale, we calculated the need for 330 subjects. An interim analysis will be conducted to determine lack of efficacy of valproate.

Study Design

• Study Type: Interventional
• Actual Enrollment: 330 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: IV Valproate for Acute Migraine. A Randomized Comparison Versus IV Metoclopramide and IV Ketorolac
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Metoclopramide Metoclopramide 10mg IVSS	Drug: Metoclopramide; 10mg IVSS
Active Comparator: Ketorolac Ketorolac 30mg IV	Drug: Ketorolac; 30g IVSS
Active Comparator: Valproate 1gm IV	Drug: Valproate; 1gm IVSS

Outcome Measures

Primary Outcome Measures

1. Headache Pain Level on a 0-10 Verbal Scale [60 minutes after receipt of medication]

   Verbal Numerical Rating scale for pain. Absolute change from baseline. This is a 0-10 scale on which 0= no pain and 10= the worst pain imaginable.

Secondary Outcome Measures

1. Participants Who Achieve Sustained Headache Freedom for 24 Hours [2- 24 hours after receipt of medication]

   Number of participants achieving a pain free state within two hours and maintaining the pain free state for 24 hours after receipt of medication

2. Satisfaction With Medication [24 hours]

   % who answer the following question affirmatively at 24 hours: Do you want to receive the same medication the next time you present to an ER with an acute migraine

3. Adverse Event [24 hours]

   % who report any adverse event after administration of investigational medication

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• IHS migraine without aura

• IHS probable migraine (all migraine without arua criteria must be met except duration may be >72 hours or <4 hours)

Exclusion Criteria:

• Allergy or contra-indication to investigational medication

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Montefiore Medical Center	Bronx	New York	United States	10467

Sponsors and Collaborators

• Montefiore Medical Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Benjamin W. Friedman, MD, Associate professor, Montefiore Medical Center
• ClinicalTrials.gov Identifier: NCT01267864
• Other Study ID Numbers: 10-01-009
• First Posted: Dec 29, 2010
• Last Update Posted: Jun 4, 2018
• Last Verified: May 1, 2018

• Keywords provided by Benjamin W. Friedman, MD, Associate professor, Montefiore Medical Center: migraine; emergency; metoclopramide; ketorolac; valproate
• Additional relevant MeSH terms: Migraine Disorders; Ketorolac; Valproic Acid; Metoclopramide

Study Results

Participant Flow

Arm/Group Title	Metoclopramide	Ketorolac	Valproate
Arm/Group Description	Metoclopramide 10mg IVSS Metoclorpamide: 10mg IVSS	Ketorolac 30mg IV Ketorolac: 30g IVSS	1gm IV Valproate: 1gm IVSS
Period Title: Overall Study
STARTED	110	110	110
COMPLETED	110	110	110
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Metoclopramide	Ketorolac	Valproate	Total
Arm/Group Description	Metoclopramide 10mg IVSS Metoclorpamide: 10mg IVSS	Ketorolac 30mg IV Ketorolac: 30g IVSS	1gm IV Valproate: 1gm IVSS	Total of all reporting groups
Overall Participants	110	110	110	330
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	34	34	33	33
Sex: Female, Male (Count of Participants)
Female	92 83.6%	93 84.5%	91 82.7%	276 83.6%
Male	18 16.4%	17 15.5%	19 17.3%	54 16.4%

Outcome Measures

1. Primary Outcome

Title	Headache Pain Level on a 0-10 Verbal Scale
Description	Verbal Numerical Rating scale for pain. Absolute change from baseline. This is a 0-10 scale on which 0= no pain and 10= the worst pain imaginable.
Time Frame	60 minutes after receipt of medication

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metoclopramide	Ketorolac	Valproate
Arm/Group Description	Metoclopramide 10mg IVSS Metoclorpamide: 10mg IVSS	Ketorolac 30mg IV Ketorolac: 30g IVSS	1gm IV Valproate: 1gm IVSS
Measure Participants	110	110	110
Mean (95% Confidence Interval) [units on a scale]	4.7	3.9	2.8

2. Secondary Outcome

Title	Participants Who Achieve Sustained Headache Freedom for 24 Hours
Description	Number of participants achieving a pain free state within two hours and maintaining the pain free state for 24 hours after receipt of medication
Time Frame	2- 24 hours after receipt of medication

Outcome Measure Data

Analysis Population Description

Please note that 1 patient in the metoclopramide arm and 1 patient in the ketorolac arm were lost-to-follow-up and did not provide data for this outcome

Arm/Group Title	Metoclopramide	Ketorolac	Valproate
Arm/Group Description	Metoclopramide 10mg IVSS Metoclorpamide: 10mg IVSS	Ketorolac 30mg IV Ketorolac: 30g IVSS	1gm IV Valproate: 1gm IVSS
Measure Participants	109	109	110
Count of Participants [Participants]	12 10.9%	17 15.5%	4 3.6%

3. Secondary Outcome

Title	Satisfaction With Medication
Description	% who answer the following question affirmatively at 24 hours: Do you want to receive the same medication the next time you present to an ER with an acute migraine
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Study participants were telephoned 24 hours after medication administration. 3 patients in the metoclopramide arm, 4 in the ketorolac arm, and 3 in the valproate arm were lost to follow-up and did not provide these data. Additionally, 1 patient in the ketorolac arm did not provide an answer to this question

Arm/Group Title	Metoclopramide	Ketorolac	Valproate
Arm/Group Description	Metoclopramide 10mg IVSS Metoclorpamide: 10mg IVSS	Ketorolac 30mg IV Ketorolac: 30g IVSS	1gm IV Valproate: 1gm IVSS
Measure Participants	107	105	107
Count of Participants [Participants]	65 59.1%	42 38.2%	28 25.5%

4. Secondary Outcome

Title	Adverse Event
Description	% who report any adverse event after administration of investigational medication
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Any adverse event reported at any assessment throughout the study period.

Arm/Group Title	Metoclopramide	Ketorolac	Valproate
Arm/Group Description	Metoclopramide 10mg IVSS Metoclorpamide: 10mg IVSS	Ketorolac 30mg IV Ketorolac: 30g IVSS	1gm IV Valproate: 1gm IVSS
Measure Participants	109	110	110
Count of Participants [Participants]	24 21.8%	33 30%	25 22.7%

Adverse Events

Time Frame	Adverse events were assessed for two hours in the emergency department after medication administration and then by telephone 24 hours later.
Adverse Event Reporting Description	Please note: 3 patients in the metoclopramide arm, 5 in the ketorolac arm, and 3 in the valproate arm did not provide data about restlessness. Also, 1 patient in the metoclopramide arm did not provide any adverse event data. Please note: Patients who reported an adverse event but did not detail what their symptom was are counted as "other"
Arm/Group Title	Metoclopramide		Ketorolac		Valproate
Arm/Group Description	Metoclopramide 10mg IVSS Metoclorpamide: 10mg IVSS		Ketorolac 30mg IV Ketorolac: 30g IVSS		1gm IV Valproate: 1gm IVSS
All Cause Mortality
	Metoclopramide		Ketorolac		Valproate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Metoclopramide		Ketorolac		Valproate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/109 (0%)		0/110 (0%)		0/110 (0%)
Other (Not Including Serious) Adverse Events
	Metoclopramide		Ketorolac		Valproate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/109 (22%)		33/110 (30%)		25/110 (22.7%)
Gastrointestinal disorders
Dyspepsia	1/109 (0.9%)		4/110 (3.6%)		2/110 (1.8%)
Investigations
Other	15/109 (13.8%)	15	20/110 (18.2%)	20	17/110 (15.5%)	17
Nervous system disorders
Restless	15/109 (13.8%)	15	10/110 (9.1%)	10	9/110 (8.2%)	9
Drowsiness	2/109 (1.8%)	2	2/110 (1.8%)	2	7/110 (6.4%)	7
Dizzy	8/109 (7.3%)	8	9/110 (8.2%)	9	6/110 (5.5%)	6

Limitations/Caveats

[Not Specified]

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.