The ACTION study: A randomized, open-label, multicenter trial comparing once-a-day extended-release morphine sulfate capsules (AVINZA®) to twice-a-day controlled-release oxycodone hydrochloride tablets (OxyContin®) for the treatment of chronic, moderate to severe low back pain

Abstract

This large, open-label, randomized, parallel-group, multicenter study compared two oral sustained-release opioids (SROs)—AVINZA® (A-MQD), morphine sulfate extended-release capsules given once a day, and OxyContin® (O-ER), oxycodone modified-release tablets given twice a day—in SRO-naive subjects ages 30 to 70 with chronic, moderate to severe low back pain. Of the 392 subjects enrolled and randomized, 266 (132 in the AMQD group and 134 in the O-ER group) completed the opioid dose titration phase and entered an eight-week evaluation phase. During the evaluation phase, A-MQD achieved significantly better pain control than O-ER, as demonstrated by a greater decrease from baseline in pain scores obtained four times daily during weeks one, four, and eight (p = 0.002). The number of breakthrough-pain rescue medication doses adjusted for the number of patient days was significantly lower in the A-MQD group (p < 0.0001). Better pain control with A-MQD was achieved with a significantly lower daily opioid dose than with O-ER (mean 69.9 mg and 91 mg morphine equivalents, respectively; p = 0.0125). Quality of sleep was significantly better with A-MQD for the entire evaluation phase (p = 0.0026). The incidence and severity of elicited opioid side effects were similar in the two groups. This trial demonstrated that once-daily A-MQD provides consistent around-the-clock pain relief in patients with low back pain. In patients who completed opioid dose titration, A-MQD was significantly better than O-ER for reducing pain and improving sleep, while requiring a lower daily opioid dose.

Pharmacotherapy for Chronic Low Back Pain

“…All patients, including opioid-experienced patients, were started on oxycodone 10 mg. The maximum dose of 50 mg is much less than the maximum doses reported in oxycodone trials (Rauck et al, 2006a). Nonetheless, if patients were underdosed with respect to analgesia, they also would be expected to have more adverse events at higher, more effective doses.…”

“…As in the previous trials, use of a flexible titration schedule allowed 67.9% of patients (morphine extended release, 65.0%; oxycodone controlled release, 70.9%) to be titrated successful. Once-daily morphine extended-release capsules provided significantly better analgesia with a lower morphineequivalent daily dose compared with oxycodone twice daily (Rauck et al, 2006a). Sleep quality was significantly better with once-daily morphine, and rescue ibuprofen use was significantly less compared with twice-daily oxycodone.…”

“…Of note, the use of fentanyl transdermal patch for opioid-naïve patients in this study is contrary to the products' approved use. (Duragesic ® , 2009) In contrast, studies of oxymorphone (Hale et al, 2007), oxycodone controlled release, and morphine extended release (Rauck et al, 2006a), and hydromorphone OROS (Wallace et al, 2007) have demonstrated efficacy in patients with chronic low back pain that was moderate to severe despite previous opioid therapy. Fentanyl may offer advantages over oral opioids for patients with compliance issues, including those with problems chewing or swallowing.…”

“…Approximately one quarter of patients discontinue clinical trials owing to adverse events (Kalso et al, 2004). Flexible titration reduces adverse events and allows the majority of patients to be titrated to an effective dose (Peniston & Gould, 2009;Rauck et al, 2006a). In 2 trials of oxymorphone extended release, nearly two thirds (348 of 575; 60.5%) of patients were successfully titrated to a well-tolerated oxymorphone extended release dose.…”

“…In a randomized, open-label trial, 392 patients with chronic low back pain were randomized to an effective, generally well-tolerated dose of once-daily morphine extended release or twice-daily oxycodone controlled release (Rauck et al, 2006a). Patients then entered an 8-week evaluation phase comparing the 2 treatments.…”