Extended-release tramadol/paracetamol in moderate-to-severe pain: a randomized, placebo-controlled study in patients with acute low back pain

Abstract

Objective:

Combinations of oral analgesics may offer several potential benefits compared with an individual agent. The objective of this study was to investigate the efficacy and safety of an extended-release, twice-daily fixed combination of 75 mg tramadol/650 mg paracetamol (DDS-06C) in the treatment of moderate-to-severe pain, using acute low back pain as a model.

Research design and methods:

In this phase III study, 277 patients with moderate-to-severe acute low back pain were randomized to 1–2 tablets of DDS-06C or placebo every 10–12 h for 2.5 days during the double-blind phase. Following the double-blind phase, patients had the option to continue for a 2.5-day open-label phase.

Clinical trial registration:

Clinicaltrials.gov (Identifier: NCT00643383)

Main outcome measures:

The primary end point was the sum of pain intensity differences (SPID) over the 50-h double-blind phase (SPID50). Secondary end points included total pain relief score over the 50-h double-blind phase (TOTPAR50), patient’s global impression of medication, and SPID over the first 4 h.

Results:

A statistically significant (p = 0.038) greater decrease in pain intensity was observed in the DDS-06C group (median SPID50: −6.0) versus placebo (median SPID50: −4.0). Greater pain relief was also observed in patients randomized to DDS-06C: the median TOTPAR50 was 13.0 for the DDS-06C group and 11.0 for placebo (p = 0.026). DDS-06C demonstrated statistically significant superior efficacy compared with placebo for the majority of the other secondary end points. Overall, 38% of patients treated with DDS-06C experienced at least one adverse event; the intensity was mild-to-moderate in 81% of cases. The most commonly reported adverse events (>5% of patients receiving DDS-06C) were nausea, dizziness, vomiting, and somnolence.

Conclusions:

Using acute low back pain, a model with a high degree of heterogeneity and intrinsic variability, DDS-06C was superior to placebo on measures of pain intensity and relief, and was well-tolerated.

Key words::

• Acute low back pain
• Analgesic
• Combination
• Extended-release
• Paracetamol
• Placebo-controlled trial
• Tramadol

Transparency

Declaration of funding

This study was supported by Labopharm Inc.

Declaration of financial/other relationships

B.L. was an investigator for this study. R.J.L. is an employee of Labopharm Inc. K.D.R. was a consultant for Labopharm Inc. S.B. is a former employee of Labopharm Inc. and consultant on this study. A.R. and S.R. were employees at Labopharm Inc. at the time that this study was conducted.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors wish to convey our deepest thanks to the patients who participated in this clinical study. We also thank INC Research, Inc. for their implementation of the study protocol and Peter Treasure, PhD, CStat (Peter Treasure Statistical Services Ltd, King's Lynn, UK) for his statistical expertise. Thanks also to Nancy Vermette for her assistance in creating tables and figures for this publication.

We are grateful for the hard work and dedication of the following principal investigators and their staff: Pierre Arsenault, MD; Armen Arslanian, MD; Richard L. Beasley, MD; Stephanie Berg, MD; Guy Chouinard, MD; Shane Christensen, MD; Lisa Cohen, DO; David Damian, MD; Pierre Dauth, MD; Waymon Drummond, MD; Didier Fay, MD; Benoit Gervais, MD; Anil Gupta, MD; Sam Henein, MD; Dan C. Henry, MD; Louise Laberge, MD; Ken Lai, MD; Ben Lasko, MD; Vaughn H. Mancha, MD; Pierre Martin, MD; Giuseppe Mazza, MD; James Miner, MD; Dennis O'Keefe, MD; Michael O'Mahony, MD; Armando Perez, MD; Alan Reichman, MD; Paul Rheault, MD; John Sutherland, MD; Guy Tellier, MD; Anthony Wade, MD; Daniel Whittington, MD.

This article was previously presented as a poster at the 13th World Congress on Pain (Montreal, Canada; August 29 – September 2, 2010).