OTC analgesics in headache treatment: open-label phase vs randomized double-blind phase of a large clinical trial.

Objective: To compare the superior efficacy of the fixed combination of acetylsalicylic acid, paracetamol, and caffeine over the single substances, which was observed in the randomized, double-blind phase of the clinical trial, with the efficacy of the respective usual nonprescription medication taken by the patients in the open-label pre-phase of the same study.

Background: The "Thomapyrin Study" showed significant superiority of the fixed combination containing acetylsalicylic acid, paracetamol, and caffeine over the combination without caffeine, the single preparations, and placebo in the treatment of headache.

Methods: Prior to the randomized treatment phase, a headache episode treated with the patient's usual nonprescription medication was recorded (open-label pre-phase). Patients assessed their pain intensity on a 100-mm visual analog scale. For the 1734 patients included in the efficacy analysis, we compared the time course of the pain intensity difference (PID) to baseline after the patients took their usual medication with the time course of the PID after intake of the randomized study medication.

Results: Time course of PID after intake of the patient's usual medication was very similar to the time course of PID after intake of the randomized study medication. After 2 hours, pain reduction was on average 43.0, 38.2, 38.1, and 37.7 mm as assessed on the visual analog scale in the group of patients who took their usual triple combination containing acetylsalicylic acid, paracetamol, and caffeine, the single agents acetylsalicylic acid, paracetamol, and ibuprofen, respectively, in the open-label phase. The corresponding mean pain reduction was 44.7, 40.7, and 39.5 mm in patients allocated to the triple combination containing acetylsalicylic acid, paracetamol, and caffeine, the single agents acetylsalicylic acid, and paracetamol, respectively, in the randomized, double-blind phase.