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Rofecoxib Versus Ibuprofen for Acute Treatment of Migraine: a Randomised Placebo Controlled Trial U K Misra, M Jose, J Kalita

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Rofecoxib Versus Ibuprofen for Acute Treatment of Migraine: a Randomised Placebo Controlled Trial U K Misra, M Jose, J Kalita 720 Postgrad Med J: first published as 10.1136/pgmj.2003.017160 on 3 December 2004. Downloaded from ORIGINAL ARTICLE Rofecoxib versus ibuprofen for acute treatment of migraine: a randomised placebo controlled trial U K Misra, M Jose, J Kalita ............................................................................................................................... Postgrad Med J 2004;80:720–723. doi: 10.1136/pgmj.2003.012393 Background: Rofecoxib is a potent cyclo-oxygenase-2 inhibitor with a long duration of action. Its role in migraine has not been systematically evaluated. Aim: To study the efficacy of rofecoxib in migraine. Method: In a randomised placebo controlled trial rofecoxib 25 mg, ibuprofen 400 mg, and placebo were compared regarding their efficacy in relieving acute migraine attack. Migraine patients with 2–6 attacks per month were recruited. Headache severity, functional disability, and severity of associated symptoms were graded on a 0–3 scale. The primary endpoint was pain relief at two hours. Relief of associated symptoms and sustained pain relief for 24 hours were also noted. See end of article for Result: One hundred and twenty four patients were randomised into rofecoxib (42), ibuprofen (40), and authors’ affiliations placebo (42) groups. One hundred and one patients were followed up: 33 on rofecoxib, 35 ibuprofen, ....................... and 33 placebo. Patients’ ages ranged from 16–62 (mean 31.4) years, and 83 were females. Pain relief Correspondence to: at two hours was noted in 45.5% on rofecoxib, 55.6% on ibuprofen, and 9.1% in the placebo group. The Professor Usha Kant Misra, associated symptoms at two hours were reduced in 39.4% on rofecoxib, 50% on ibuprofen, and 9.1% in Department of Neurology, the placebo group. Sustained 24 hour pain relief was noted in 36.4% on rofecoxib, 41% on ibuprofen, Sanjay Gandhi PGIMS, Raebareily Road, Lucknow and 6.1% in the placebo group. In the ibuprofen group, five patients had abdominal pain but there were 226014, India; ukmisra@ no side effects in those on rofecoxib or in the control group. Both rofecoxib and ibuprofen were sgpgi.ac.in significantly effective in relieving pain, associated symptoms at two hours, and in sustained pain relief. Submitted 9 July 2003 There was no significant difference between rofecoxib and ibuprofen in aborting acute migraine attacks. Accepted 28 October 2003 Conclusions: Both ibuprofen and rofecoxib were superior to placebo in aborting an acute migraine attack, ....................... and there was no significant difference in their efficacy in an acute migraine attack. igraine is one of the commonest causes of headache, investigator (JK) and the responses were evaluated by and can be severe and last for hours to days. It is one another (MJ). The blinding was done by giving identical Mof the commonest causes of absence from work and packets containing the medication; however, the tablets were results in a considerable economic burden on society. Pre- not of identical appearance. The patients were asked to sently acetaminophen, non-steroidal anti-inflammatory drugs, maintain a headache diary and instructed to note the http://pmj.bmj.com/ ergot alkaloids, and triptans are used for treatment of an acute headache severity, functional disability, and associated sym- migraine attack. The choice of abortive treatment is based on its ptoms such as nausea, vomiting, photophobia, and phono- efficacy in relieving pain, lack of side effects, and cost. Rofecoxib phobia before and after the treatment. Severity of headache is a selective cyclo-oxygenase (COX)-2 inhibitor with good gas- and functional disability were graded on a 0–3 scale: grade trointestinal tolerance. In the treatment of arthritis rofecoxib 0 = normal, grade 1 = mild headache, grade 2 = moderate was more effective in providing symptomatic relief of pain com- headache, and grade 3 = severe headache. Similarly pared with placebo.1 Acetaminophen and celecoxib were similar functional disability was graded as 0 = normal, 1 = daily in efficacy to ibuprofen, diclofenac, naproxen, and nabume- activities mildly impaired, 2 = daily activities severely on September 30, 2021 by guest. Protected copyright. tone.2 In the available literature, we could not find a randomised impaired, and 3 = unable to perform daily activities, 4 placebo controlled trial on the efficacy of rofecoxib in migraine. requiring bed rest. Patients with grade 3 functional disability The present study, therefore, aims at evaluating the efficacy of needing bed rest during attacks and those with vomiting 20% rofecoxib and ibuprofen with placebo in the treatment of an or more of the time during a migraine attack were excluded. acute attack of migraine. The severity of associated symptoms such as nausea, vomiting, photophobia, and phonophobia were also graded on a 0–3 scale (0 = normal, 1 = mild, 2 = moderate, and 3 METHODS = severe). A detailed clinical examination was carried out in This randomised placebo controlled trial was conducted in a all the patients. The patients were randomly prescribed tertiary care teaching hospital between January 2001 and rofecoxib 25 mg, ibuprofen 400 mg, or placebo (calcium January 2002. The patients were recruited from the out- 250 mg) kept in an identical looking packet. The patients patient service of the neurology department. The protocol was were advised to take the study medication if headache was approved by the institute’s ethics committee and patients moderate or severe. Rescue medication (sumatriptan 100 mg gave consent to participate in the trial and fill in the or piroxicam 20 mg) was advised only after two hours, if headache diary. The patients had at least a 12 month history moderate or severe headache persisted (fig 1). of migraine with or without aura as defined by the criteria of Outcome was evaluated after one month or after two or more the International Headache Society.3 All the patients were attacks, which were documented in the diary. The following over 16 years of age and none had more than six attacks of three measures of efficacy were evaluated: (1) percentage of migraine per month. The patients were randomised using random number tables into three groups: rofecoxib, ibupro- Abbreviations: CI, confidence interval; COX, cyclo-oxygenase; OR, fen, and placebo. The randomisation was done by one odds ratio www.postgradmedj.com Rofecoxib v ibuprofen for treatment of migraine 721 Postgrad Med J: first published as 10.1136/pgmj.2003.017160 on 3 December 2004. Downloaded from Figure 1 Profile of randomised Registered/eligible patients (n = 124) controlled trial. Not randomised (n = 0) Reasons (n = 0) Randomisation (n = 124) Rofecoxib Ibuprofen Placebo Received standard intervention Received standard intervention Received placebo as allocated as allocated (n = 42) as allocated (n = 40) (n = 42) Did not receive standard Did not receive standard Did not receive placebo as intervention as allocated (n = 0) intervention as allocated (n = 0) allocated (n = 0) Followed up (n = 33) Followed up (n = 35) Followed up (n = 33) Timing of primary and Timing of primary and Timing of primary and secondary outcome: 2 attacks secondary outcome: 2 attacks secondary outcome: 2 attacks or 1 month or 1 month or 1 month Withdrawn (n = 0) Withdrawn (n = 1) Withdrawn (n = 0) Intervention ineffective (n = 18) Intervention ineffective (n = 16) Placbo ineffective (n = 30) Lost to follow up (n = 9) Lost to follow up (n = 6) Lost to follow up (n = 8) Other (n = 0) Other (n = 0) Other (n = 0) Completed trial (n = 33) Completed trial (n = 35) Completed trial (n = 33) patients with pain relief at two hours, (2) percentage of patients 99% of the patients. Vomiting in these patients, however, did free of associated symptoms—that is, absence of nausea, vomit- not exceed 20% of the time of the migraine attack. ing, photophobia, or phonophobia, and (3) percentage of patients with 24 hours of sustained pain relief—that is, absence Efficacy analysis of recurrence of headache and lack of requirement of antimi- In the 101 patients included in this study, active drugs more graine medication for 24 hours. Headache recurrence was frequently aborted the migraine attack compared with defined as the recurrence of moderate to severe headache placebo at two hours. In the rofecoxib group 45.5% of the within 24 hours of dosing in patients who initially had relief of patients were relieved of pain and 39.4% were free of pain two hours after medication. Any side effects of the drugs associated symptoms at two hours. In the ibuprofen group up to 24 hours after ingestion were also noted. 55.6% patients were relieved of pain and 50% were free of http://pmj.bmj.com/ This study was designed as a non-inferiority trial expecting associated symptoms, while in the placebo group it was 9.1% rofecoxib to be as good as ibuprofen and superior to placebo. for both measures. In the rofecoxib group, sustained pain In order to detect the difference between the two drugs alpha relief was present in 36.4% patients, in the ibuprofen group risk was taken as 5%, critical difference in the drugs was 41.7%, and in control group only 6.1%. Two hour pain relief taken as 10%, and the power calculation was done according 5 was significantly superior in rofecoxib (odds ratio (OR) 8.33, to the method described by Agresti. Sample size was based 95% confidence interval (CI) 2.12 to 32.65, power 0.83) and on the response rate. Pain relief at two hours was considered ibuprofen (OR 12.50, 95% CI 3.22 to 48.55, power 0.82) on September 30, 2021 by guest. Protected copyright. important (efficacy of the drug) and the standard deviation compared with placebo. In relieving associated symptoms ¡ was taken as 2. Based on this criterion the sample size was rofecoxib (OR 6.5, 95% CI 1.64 to 25.76, power 0.83) and calculated to be at least 30 in each group.
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