Clinical trial NCT02664116: IM Ketorolac vs Cambia for the Acute Treatment of Severe Migraine
Official title: IM Ketorolac vs Diclofenac Potassium Powder for Oral Solution (Cambia) for the Acute Treatment of Severe Migraine
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Migraine Headache
Keywords: Severe Migraine Headache
Lead sponsor: Scripps Health
Sponsor class: OTHER
Collaborators: name: Depomed
First posted: 2016-01-26
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This research will be conducted to see if the oral drug Cambia is as effective in relieving severe migraine headaches as the injectable drug ketorolac.

Detailed description: The treatment of severe migraine often requires a patient office visit or treatment in the ER or urgent care setting. This is due to the minimal efficacy of PO treatments once migraine is severe, and therefore the need for parenteral treatments. IM Ketorolac is one mainstay of parenteral treatment. There is an unmet need for effective at-home treatment regimens for severe migraine. Despite FDA approval of Cambia for acute migraine treatment, insurance is reticent to cover the treatment due to higher cost in comparison to generic diclofenac tablets, despite superior efficacy of Cambia in comparison to generic diclofenac tablets (Diener, Cephalalgia 2006). One objective of this study would be to provide rationale to justify the insurance coverage of this treatment in comparison to generic tablets, because at home treatment is less costly than office visit or emergency department visit to receive IM ketorolac.

A previous study of Cambia demonstrated that this formulation of diclofenac potassium for oral solution is effective in reducing pain intensity within 30 minutes, which may be related to the 15-minute Tmax associated with this formulation. The rapid-onset benefits were sustained through 24 hours post-treatment (Lipton, Cephalalgia 2010)

Eligibility criteria: Inclusion Criteria:

* Patients who meet IHS criteria for migraine
* Age 18 to 65
* At least 2 migraine attacks per month
* Able to give written consent
* Willing to complete the entire course of the study
* Current headache duration greater than or equal to 36 hours

Exclusion Criteria:

* Pregnant or nursing
* Significant medical or psychiatric disease
* History of gastritis, gastric ulcer, GI bleed
* Renal insufficiency
* Hepatic insufficiency
* History of opioid dependence within the last 10 years or currently
* Any current or prior use of DICLOFENAC POTASSIUM POWDER FOR ORAL SOLUTION (CAMBIA)
* Past allergic reaction to DICLOFENAC or other NSAIDs

Primary outcomes:
measure: Pain relief, 0-3 scale
timeFrame: Change from baseline pain rating at 5, 10, 15, 30, and 60 minutes post intervention
measure: Pain free response, 0-3 scale
timeFrame: 2 hours post intervention
measure: Sustained pain free response, 0-3 scale
timeFrame: 24 hours post intervention
Secondary outcomes:
measure: Change in severity of migraine associated symptoms
timeFrame: 5, 10, 15, 30, 60, 120 minutes and 24 hours post intervention
measure: Return to function
timeFrame: 24 hours post intervention
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
Study officials:
affiliation: Scripps Health
name: Emily Rubenstein Engel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Factor SA, Jankovic J. Randomized trial of IV valproate vs metoclopramide vs ketorolac for acute migraine. Neurology. 2014 Oct 7;83(15):1388-9. doi: 10.1212/01.wnl.0000455698.16732.0a. No abstract available.
citation: Garnock-Jones KP. Diclofenac potassium powder for oral solution: a review of its use in patients with acute migraine. CNS Drugs. 2014 Aug;28(8):761-8. doi: 10.1007/s40263-014-0186-y.
citation: Friedman BW, Garber L, Yoon A, Solorzano C, Wollowitz A, Esses D, Bijur PE, Gallagher EJ. Randomized trial of IV valproate vs metoclopramide vs ketorolac for acute migraine. Neurology. 2014 Mar 18;82(11):976-83. doi: 10.1212/WNL.0000000000000223. Epub 2014 Feb 12.
citation: Taggart E, Doran S, Kokotillo A, Campbell S, Villa-Roel C, Rowe BH. Ketorolac in the treatment of acute migraine: a systematic review. Headache. 2013 Feb;53(2):277-87. doi: 10.1111/head.12009. Epub 2013 Jan 8.
citation: Lipton RB, Grosberg B, Singer RP, Pearlman SH, Sorrentino JV, Quiring JN, Saper JR. Efficacy and tolerability of a new powdered formulation of diclofenac potassium for oral solution for the acute treatment of migraine: results from the International Migraine Pain Assessment Clinical Trial (IMPACT). Cephalalgia. 2010 Nov;30(11):1336-45. doi: 10.1177/0333102410367523. Epub 2010 Apr 7.
citation: Duarte C, Dunaway F, Turner L, Aldag J, Frederick R. Ketorolac versus meperidine and hydroxyzine in the treatment of acute migraine headache: a randomized, prospective, double-blind trial. Ann Emerg Med. 1992 Sep;21(9):1116-21. doi: 10.1016/s0196-0644(05)80654-7.
citation: Orr SL, Aube M, Becker WJ, Davenport WJ, Dilli E, Dodick D, Giammarco R, Gladstone J, Leroux E, Pim H, Dickinson G, Christie SN. Canadian Headache Society systematic review and recommendations on the treatment of migraine pain in emergency settings. Cephalalgia. 2015 Mar;35(3):271-84. doi: 10.1177/0333102414535997. Epub 2014 May 29.
citation: Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: the american headache society evidence assessment of migraine pharmacotherapies. Headache. 2015 Jan;55(1):3-20. doi: 10.1111/head.12499.
citation: Diener HC, Montagna P, Gacs G, Lyczak P, Schumann G, Zoller B, Mulder LJ, Siegel J, Edson K. Efficacy and tolerability of diclofenac potassium sachets in migraine: a randomized, double-blind, cross-over study in comparison with diclofenac potassium tablets and placebo. Cephalalgia. 2006 May;26(5):537-47. doi: 10.1111/j.1468-2982.2005.01064.x.
citation: Engel ER, Cheng J. IM ketorolac vs diclofenac potassium powder for oral solution for the acute treatment of severe migraine: a randomized controlled trial. Neurol Sci. 2020 Mar;41(3):537-542. doi: 10.1007/s10072-019-04157-y. Epub 2019 Dec 12.