Safety and efficacy of oxycodone/naloxone vs. oxycodone vs. morphine for the treatment of chronic low back pain: results of a 12 week prospective, randomized, open-label blinded endpoint streamlined study with prolonged-release preparations

Abstract

Background:

Opioid-induced constipation (OIC) is the most prevalent patient complaint associated with opioid use and interferes with analgesic efficacy.

Objectives:

This PROBE trial compares the overall safety and tolerability of oxycodone/naloxone (OXN) with those of traditional opioid therapy with oxycodone (OXY) or morphine (MOR) in the setting of the German healthcare system.

Research design and methods:

This was a prospective, randomized, open-label, blinded endpoint (PROBE) streamlined study (German pain study registry: 2012-0012-05; EudraCT: 2012-001317-16), carried out in 88 centers in Germany, where a total of 453 patients, requiring WHO step III opioids to treat low back pain, were randomized to OXN, OXY or MOR (1:1:1) for 3 months. The primary outcome was the percentage of patients without adverse event-related study discontinuations who presented with a combination of a ≥50% improvement of pain intensity, disability and quality-of-life and a ≤50% worsening of bowel function at study end.

Results:

Significantly more OXN patients met the primary endpoint (22.2%) vs. OXY (9.3%; OR: 2.80; p < 0.001) vs. MOR (6.3%; OR: 4.23; p < 0.001), with insignificant differences between OXY vs. MOR (p = 0.155). A ≥50% improvement of pain intensity, functional disability and quality-of-life has been found for OXN in 75.0/61.1/66.0% of patients and thus for all parameters significantly more than with OXY (58.9/49.0/48.3; p < 0.001 for each) or MOR (52.5/46.2/37.3; p < 0.001 for each). A total of 86.8% of OXN patients kept normal BFI scores during treatment, vs. 63.6% for OXY (p < 0.001) vs. 53.8% for MOR (p < 0.001). Overall 189 TEAEs (OXN: 45, OXY: 69, MOR: 75) in 92 patients (OXN: 21, OXY: 44, MOR: 37) occurred, most gastrointestinal (50.8%). One limitation is the open-label design, which presents the possibility of interpretive bias.

Conclusion:

Under the conditions of this PROBE design, OXN was associated with a significantly better tolerability, a lower risk of OIC and a significantly better analgesic efficacy than OXY or MOR.

Keywords: :

• Bowel function
• Chronic pain
• Constipation
• Naloxone
• Oxycodone
• PROBE
• Quality-of-life

Transparency

Declaration of funding

This study was sponsored by an unrestricted scientific grant from Mundipharma, Germany.

Authors’ contributions: The concept for this PROBE study was developed by the Institute for Neurological Sciences (IFNAP) on behalf of the German Pain Association (Deutsche Gesellschaft für Schmerzmedizin, DGS) and the German Pain League (Deutsche Schmerzliga, DSL). The study was realized by an independent CRO and partly (<49%) sponsored by an unrestricted scientific grant from Mundipharma, Germany. Neither the study sponsor, nor any of its employees exerted any influence on the conduct of the study, or on analyses, interpretation and publication of the results. Both authors were involved in drafting the article or revising it critically for important intellectual content, and both authors read and approved the final manuscript to be published.

Declaration of financial/other relationships

M.A.U. and G.H.H.M.-S. have disclosed that they are physicians and independent of any significant/relevant financial or other relationship to the sponsor, except for minor reimbursements for occasional lecture or consulting fees.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgments

Data of this study have been presented at the World Pain Congress of the International Association for the Study of Pain (IASP), 6–11 October 2014, Buenos Aires, Argentina.