Thursday, June 16, 2016

Ketorolac nasal spray for the treatment of migraine

Rao AS, Gelaye B, Kurth T, Dash PD, Nitchie H, Peterlin BL. A Randomized Trial of Ketorolac vs Sumatripan vs Placebo Nasal Spray (KSPN) for Acute Migraine. Headache. 2016 Feb;56(2):331-40.


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.

From the article

There are several limitations and strengths of the KSPN migraine study. While the total number of participants enrolled in this single site study was relatively small (n = 54), the cross-over designed allowed for evaluation of over 150 acute migraine attacks and helped to reduce participant variation, such as can occur in multicenter studies and those with parallel treatment arm designs. Additionally although only one primary outcome was set, a wide range of important secondary outcome parameters were a priori specified and evaluated. Finally, the most common adverse effects reported for both ketorolac NS and sumatriptan NS were nasal burning (ketorolac > sumatriptan) and an unusual taste (sumatriptan > ketorolac). Both were mild to moderate for the majority of patients treated with active treatments. Further, although 3.9% of participants reported severe nasal burning with ketorolac NS, no participants withdrew from the study due to this side effect. In the previous trial evaluating ROX-828 vs placebo, nasal discomfort was also the most common adverse event, despite the inclusion of lidocaine. Thus, while it is possible that research personnel and participants in the KSPN study may have been able to "guess" which treatment was utilized based on the presence of nasal burning and dysgeusia, given these symptoms were reported by both active treatment arms as well as those given placebo we do not believe it substantially affected the blinding of this study.

The KSPN migraine study demonstrates that the nonsteroidal anti-inflammatory NS formulation of ketorolac is superior to placebo and is non-inferior to the triptan NS formulation of sumatriptan for the acute abortive treatment of moderate to severe migraine. As with triptan intranasal formulations, intranasal ketorolac may be particularly appropriate to consider for acute abortive migraine treatment when nausea or oral medications are not able to be used, and additionally offers an effective alternative for those who cannot or do not want to use a triptan NS.

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