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


OBJECTIVE
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.


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.


CONCLUSIONS
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.
Institute for Neurological Sciences , Nuernberg , Germany.
Michael A
MA
Ueberall
Gerhard H H
GH
Mueller-Schwefe
D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003248:Constipation / Q000139:chemically induced; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D005260:Female; D005858:Germany; D006801:Humans; D017116:Low Back Pain / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects / Q000627:therapeutic use*; D009270:Naloxone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010098:Oxycodone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D055815:Young Adult
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D009270:Naloxone; D009020:Morphine; D010098:Oxycodone
Bowel function; Chronic pain; Constipation; Naloxone; Oxycodone; PROBE; Quality-of-life