A Randomized Trial of Ketorolac vs. Sumatripan vs. Placebo Nasal Spray (KSPN) for Acute Migraine

Abstract

Objective: To compare the efficacy of ketorolac nasal spray (NS) vs. placebo and sumatriptan NS for the acute treatment of migraine.

Methods: This was a randomized, double-blind, placebo and active-comparator, crossover study. Adult migraineurs were randomized to ketorolac NS 31.5 mg, sumatriptan NS 20 mg, or placebo to treat three moderate to severe migraine attacks and switched treatments with each attack. Patients seeking headache care at a headache center or in response to community advertisement were recruited. Adult participants with episodic migraine who experienced ≥2 migraine attacks per month were eligible for the Ketorolac vs. Sumatriptan vs. Placebo Nasal Spray migraine study. Participants were randomized to treatment arms by a research pharmacist, in a 1:1:1 ratio using computer-generated lists. The primary outcome was 2-hour pain relief. Secondary outcomes included 2-hour pain freedom and absence of migraine associated symptoms, and 24-hour sustained pain relief and pain freedom.

Results: Of the 72 randomized participants, 54 (75%) treated at least one attack and 49 (68%) completed all three treatments, for a total of 152 treated migraine attacks. Both ketorolac NS (72.5%, P < .001) and sumatriptan NS (69.4%, P = .001) were more effective than placebo (38.3%) for 2-hour pain relief and 2-hour pain freedom (ketorolac: 43.1%, P = .004; sumatriptan: 36.7%, P = .046; placebo: 18.4%). Ketorolac NS, but not sumatriptan NS, was more effective than placebo in 2-hour absence of nausea. Both ketorolac NS and sumatriptan NS were more effective than placebo for 24-hour sustained pain relief (ketorolac: 49%, P < .001; sumatriptan: 31%, P = .01, placebo: 20%). Only ketorolac NS was superior to placebo for 24-hour (ketorolac: 35.3%, P = .003; sumatriptan: 22.4%, P = .18, placebo: 12.2%) sustained pain freedom. Nasal burning and dysgeusia were the most common adverse effects for active treatments.

Conclusions: This study supports that ketorolac NS is superior to placebo and that it is non-inferior to sumatriptan NS for the acute abortive treatment of migraine.

Trial registration: ClinicalTrials.gov NCT01807234.

Keywords: intranasal; ketorolac; migraine; moderate to severe pain; nasal spray; nonsteroidal anti-inflammatory; sumatriptan; treatment; triptan.

Conflict of interest statement

Conflict of Interest: Dr. Peterlin: Grant support from the Landenberger Foundation and GSK within the past 5 years for research studies unrelated to current manuscript.

© 2016 American Headache Society.

Figures

Fig. 1

Consort flow diagram for the Ketorolac vs Sumatripan vs Placebo Nasal Spray migraine study.

Fig. 2

Time-to-pain-relief. The time-to-pain-relief in the Ketorolac vs Sumatripan vs Placebo Nasal Spray migraine study was conducted using survival analysis, an approach taking into account all time points between 10 and 120 minutes. Hazard ratios (HR) are calculated indicating whether each of the two treatment groups are superior to placebo. Both ketorolac NS (HR 2.34; 95% CI 1.88–3.04) and sumatriptan NS (HR 2.00; 95%CI: 1.53–2.61) had a faster time to pain relief at any time in the 2-hour period after treatment vs placebo. There was no difference between ketorolac NS and sumatriptan NS, P =.129. Smoothed hazard curves are presented above by treatment group. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]