Grosset, A.B., Roberts, M.S., Woodson, M.E., Shi, M., Swanton, R.E., Reder, R.F., & Buckley, B.J. (2005). Comparative efficacy of oral extended-release hydromorphone and immediate-release hydromorphone in patients with persistent moderate to severe pain: Two randomized controlled trials. Journal of Pain and Symptom Management, 29, 584–594.

To compare the efficacy of oral extended-release hydromorphone (HHER) administered every 24 hours with that of immediate-release hydromorphone (HHIR) administered four times daily

Patients were titrated to a stable HHER dose and randomized to individualized doses of HHER or HHIR for three to seven days before crossover to the second treatment. Nonrandomized, open-label titration phase for HHER occurred before double-blind phase.

• The sample was composed of 344 enrolled patients. Investigators analyzed data relative to 217 patients.
• Mean patient age was 58.3 years. Seventy-six patients were age 65 or older; 21 patients were age 75 or older.
• All patients had persistent moderate to severe pain related or unrelated to cancer.

The study was conducted in 37 sites in the United States.

Multicenter, randomized double-blind, crossover study

Mean of average pain intensity (API) scores, rated on a 0–10 scale, for the last two days before the pharmacokinetics/pharmacodynamics day of each double-blind period

Difference in treatments (HHER versus HHIR) in study 1 was 0.17 with a 90% CI. The difference in study 2 was 0.07 with a 90% CI. Authors noted no significant treatment-related difference in API scores or the amount of breakthrough medication used. Adverse events were opioid-related.

• The study was designed without a washout period between the crossover phases.
• Extended-release hydromorphone is no longer available in the United States.