Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study

Abstract

Aims and methods: In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets.

Results: Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57-1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82-1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated.

Conclusion: The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf.

Figure 1

Profile of subject disposition during the course of the study and inclusion in the analysis data sets: safety population (SP), intention-to-treat sample (ITT), per-protocol sample (PP)*. *Four patients treated with Indoprocaf, three with TBS (adverse event = 2 and withdrew consent = 1) and one with EFFE (adverse event), and three patients treated with sumatriptan (adverse event = 1, withdrew consent = 1 and lost to follow-up = 1) discontinued at any time during the study

Figure 2

Cumulative pain-free rates without use of rescue medication in the total attacks (A) with Indoprocaf or sumatriptan and (B) with Indoprocaf-coated tablets (tbs) or Indoprocaf-effervescent tablets (effe) (intention-to-treat sample)

Figure 3

Total pain-free rate: percentage of attacks pain-free at 5 h after first dose of Indoprocaf or sumatriptan, or after second dose of study drug used as rescue medication (χ²-test; intention-to-treat sample)

Figure 4

Summary of results obtained treating the total attacks with Indoprocaf (n = 276 attacks) or sumatriptan (n = 264 attacks) (intention-to-treat sample)

Figure 5

(A) Percentage of attacks pain-free at 2 h postdose with Indoprocaf-coated tablets (tbs) or Indoprocaf-effervescent tablets (effe) without use of rescue medication; (B) total pain-free rate: percentage of attacks pain-free at 5 h after first dose of Indoprocaf-coated tablets (tbs) or Indoprocaf-effervescent tablets (effe) or after second dose of study drug used as rescue medication (χ²-test; intention-to-treat sample)