OTC Analgesics in Headache Treatment: Open-Label Phase vs Randomized Double-Blind Phase of a Large Clinical Trial

Authors

  • Volker Pfaffenrath MD,

    1. From Neurological Practice, Leopoldstrasse, Munich, Germany (V. Pfaffenrath); Department of Neurology, University Duisburg-Essen, Essen, Germany (H-C. Diener); Department of Neurology, Cologne City Hospitals, Cologne, Germany (L. Pageler); Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany (H. Peil and B. Aicher).
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  • Hans-Christoph Diener MD, PhD,

    1. From Neurological Practice, Leopoldstrasse, Munich, Germany (V. Pfaffenrath); Department of Neurology, University Duisburg-Essen, Essen, Germany (H-C. Diener); Department of Neurology, Cologne City Hospitals, Cologne, Germany (L. Pageler); Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany (H. Peil and B. Aicher).
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  • Lutz Pageler MD,

    1. From Neurological Practice, Leopoldstrasse, Munich, Germany (V. Pfaffenrath); Department of Neurology, University Duisburg-Essen, Essen, Germany (H-C. Diener); Department of Neurology, Cologne City Hospitals, Cologne, Germany (L. Pageler); Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany (H. Peil and B. Aicher).
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  • Hubertus Peil PhD,

    1. From Neurological Practice, Leopoldstrasse, Munich, Germany (V. Pfaffenrath); Department of Neurology, University Duisburg-Essen, Essen, Germany (H-C. Diener); Department of Neurology, Cologne City Hospitals, Cologne, Germany (L. Pageler); Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany (H. Peil and B. Aicher).
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  • Bernhard Aicher PhD

    1. From Neurological Practice, Leopoldstrasse, Munich, Germany (V. Pfaffenrath); Department of Neurology, University Duisburg-Essen, Essen, Germany (H-C. Diener); Department of Neurology, Cologne City Hospitals, Cologne, Germany (L. Pageler); Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany (H. Peil and B. Aicher).
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  • Conflict of Interest: Dr. Volker Pfaffenrath received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: Addex Pharma, Allergan, Almirall, AstraZeneca, Bayer Vital, Berlin Chemie, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen-Cilag, Lilly, 3M Medica, MSD, Novartis, Pfizer, Schaper and Brümmer, Sanofiaventis, Weber & Weber. Dr. Volker Pfaffenrath has no ownership interest and does not own stocks of any pharmaceutical company.
    Prof. Hans-Christoph Diener received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: Addex Pharma, Allergan, Almirall, AstraZeneca, Bayer Vital, Berlin Chemie, CoLucid, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Grünenthal, Janssen-Cilag, Lilly, La Roche, 3M Medica, MSD, Novartis, Johnson & Johnson, Pierre Fabre, Pfizer, Schaper and Brümmer, Sanofiaventis, Weber & Weber. Financial support for research projects was provided by Allergan, Almirall, AstraZeneca, Bayer, GSK, Janssen-Cilag, Pfizer. Headache research at the Department of Neurology in Essen is supported by the German Research Council (DFG), the German Ministry of Education and Research (BMBF), and the European Union. Dr. H-C. Diener has no ownership interest and does not own stocks of any pharmaceutical company.
    Dr. Lutz Pageler has no conflict of interest.
    Drs. Hubertus Peil and Bernhard Aicher are employees of Boehringer Ingelheim Pharma GmbH & Co. KG.

V. Pfaffenrath, Neurological Practice, Leopoldstrasse 59, D 80802 Munich, Germany.

Abstract

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.

Conclusions.— The efficacy results from double-blind, randomized clinical trials with nonprescription analgesics can be generalized and applied to everyday conditions provided patients and study design are selected carefully.

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