Meissner, W., Leyendecker, P., Mueller-Lissner, S., Nadstawek, J., Hopp, M., Ruckes, C., . . . Reimer, K. (2009). A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation. European Journal of Pain (London, England), 13, 56-64.

DOI Link

Study Purpose

To assess the impact of orally administered prolonged-release (PR) naloxone on the analgesic effectiveness of PR oxycodone and on constipation in patients with severe chronic pain.

Intervention Characteristics/Basic Study Process

The study comprised three phases:

  1. Patients entered either a two-week titration or a seven-day run-in period. Patients were individually titrated and stabilized on an oxycodone PR dose of 40, 60, or 80 mg/day.
  2. Patients were randomized to four study groups, each comprising a balanced ratio of 40-, 60-, or 80-mg PR oxycodone with placebo or 10- to 40-mg naloxone. Rescue pain medication (up to five 10-mg oxycodone doses per week) was allowed during the maintenance phase.
  3. In a two-week open-label phase, patients stopped naloxone therapy and continued PR oxycodone.

Sample Characteristics

  • The study reported on a sample of 202 patients aged older than 18 years, with a mean age of 53.8 years.
  • The sample comprised 75 men (37.1%) and 127 women (62.9%).
  • Only 2.5% of the original 202 screened patients had cancer.
  • Most common pain-causing diseases or conditions were back pain (24.3%) and postoperative complications (15.3%).
  • Mean duration of pain was 149.3 months.

Setting

  • Multi-site
  • 28 sites in Germany

Study Design

This was a prospective, placebo-controlled, randomized, double-blind, parallel-group, phase II study.

Measurement Instruments/Methods

  • Bowel Function Index (BFI)
  • Numerical Analog Scale (NAS) for pain assessment

Results

  • At week 6, BFI score was statistically significantly different between the 40-mg naloxone and placebo control groups, showing a decrease of severity in bowel dysfunction with naloxone (p = 0.004). 
  • At the end of week 8, both 20- and 40-mg naloxone groups had significant differences in BFI scores compared with placebo (p < 0.05).
  • No differences existed in mean pain scores between treatment groups at any study time points.
  • Titration of participants off of PR oxycodone/naloxone back to single PR oxycodone regimens during the open-label phase resulted in decreased bowel function, and BFI scores returned almost to baseline.
  • The incidence of adverse events (AEs), most of which were mild to moderate, was comparable across all treatment groups, although the number of AEs increased along with naloxone dosage.

Conclusions

The study provided evidence that a combination of PR oxycodone/PR naloxone in a 2:1 ratio could enable patients with chronic pain to achieve both adequate pain control and bowel evacuation function.

Limitations

The study only looked at oxycodone for pain control and did not include many patients with cancer.

Nursing Implications

An oral combination of PR oxycodone/PR naloxone in a 2:1 ratio seems to improve bowel function without compromising analgesia in patients with chronic pain. Additional study should include patients with cancer and a variety of other opioids.