Efficacy and tolerability of DHEP-heparin plaster in reducing pain in mild-to-moderate muscle contusions: a double-blind, randomized trial

Abstract

Objectives:

To investigate if the 180-mg diclofenac epolamine and heparin sodium 5600 IU medicated plaster (DHEP-heparin) is more effective for pain reduction in mild-to-moderate contusions than the reference diclofenac epolamine 180 mg plaster (DHEP).

Research design and methods:

This multicenter, multinational, prospective, double-blind versus reference comparator and versus placebo, controlled trial had balanced random assignment in three parallel treatment groups. The DHEP-heparin medicated plaster was compared to the DHEP medicated plaster and a placebo medicated plaster. A total of 331 outpatients, aged ≥18 and ≤65 years, with unilateral mild-to-moderate muscle contusion, pain on standardized movement of ≥50 mm, and superficial hematoma of ≤10 × 14 cm² completed the study. Plasters were applied each morning, for ≥20 hours daily for 14 consecutive days. Outcomes were assessed in three visits, over 14 days, plus patients’ daily self-assessment.

Clinical trial registration:

05DCz/FHp11 – Eudra CT n: 2005-003829-31

Main outcome measures:

Primary efficacy endpoint was mean change from baseline in pain on movement after 3 days of treatment, compared between groups. Secondary efficacy endpoints included mean daily change from baseline in pain on movement during treatment, pain level as assessed at control visits after 7 and 14 days, time (days) to hematoma disappearance based on patients’ daily evaluations, rescue medication use, and overall treatment efficacy as judged by both patients and investigators.

Results:

Pain progressively declined in all groups, more rapidly in DHEP-heparin recipients, compared to DHEP, and in both active treatment groups compared to placebo. Adverse events were recorded in 24 of the 355 (6.7%) exposed patients, and generally resolved without need to interrupt treatment.

Conclusion:

The DHEP-heparin plaster is superior to the reference DHEP plaster in reducing pain associated with mild-to-moderate muscle contusion. Both active treatments were significantly more effective than placebo, and each showed a comparably favorable, placebo-like safety profile.

Keywords::

• Contusion
• DHEP-heparin
• Diclofenac epolamine
• Drug therapy
• Hematoma
• Heparin
• Pain
• Pain on movement

Transparency

Declaration of funding

This study was sponsored by IBSA, Institut Biochimique SA, Pambio-Noranco, Switzerland.

Declaration of financial/other relationships

S.R. and B.G. are employees of IBSA. The other authors have no conflicts of interest that are directly relevant to the content of this study. CMRO peer reviewers on this manuscript have no relevant financial relationships to disclose.

Acknowledgments

Editorial assistance for the preparation of this manuscript was provided by inScience Communications, a Wolters Kluwer business; this assistance was funded by IBSA.

Study management and monitoring activities were carried out by the Contract Research Organization ECRON ACUNOVA, Breitenbachstraße 23, 13509 Berlin, Germany (formerly ECRON Gmbh, at the time the study was conducted).

Statistical analysis was carried out by CROS NT s.r.l., Via Germania 2, 37135 Verona, Italy.

The authors thank all the investigators involved in the study: MUDr. Martin Bocek (Brno – CZ), MUDr. Pavel Brejla (Melník – CZ), MUDr. Aleš Chaloupka (Hradec Králové – CZ), Dr. med. Volker Erben (Asperg – D), Dr. med. Matthias Eyck (Berlin – D), MUDr. Jan Filipinsky (Brno – CZ), Dr. med. Stefan Jünger (Berlin – D), Dr. med. Friedhelm Heber (Neu-Ulm – D), Dr. med. Robert Heger (Leonberg – D), MUDr. Jirí Holubár (Praha – CZ), Dr. med. Werner Kneer (Stockach - D), MUDr. Alexandr Kučera (Praha – CZ), Dr. med. Dieter Marx (Berlin – D), Dr. med. Bernd Metscher (Berlin – D), MUDr. Jirí Neumann (Hradec Králové – CZ), MUDr. Pavel Pacák (Ceské Budejovice – CZ), MUDr. František Picek (Praha – CZ), Dr. med. Dieter Veith (Emmendingen – D).

Notes

*Flector and Flectoparin Tissugel are registered trademarks of IBSA Institut Biochimique SA, Pambio-Noranco, Switzerland

†Mild muscle contusion: retains near normal-associated joint range of movement; localised tenderness; no gait alteration. Moderate muscle contusion: retention of 75% of the affected joint range of movement; swollen, tender muscle mass; antalgic gait.