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Dose Equivalence of Immediate-Release Hydromorphone and Once-Daily Osmotic-Controlled Extended-Release Hydromorphone: A Randomized, Double-Blind Trial Incorporating a Measure of Assay Sensitivity

  • Ricardo A. Cruciani
    Correspondence
    Address reprint requests to Ricardo A. Cruciani, MD, PhD, Department of Pain Medicine and Palliative Care, Beth Israel Medical Center, New York, NY 10003.
    Affiliations
    Department of Pain Medicine and Palliative Care, Beth Israel Medical Center, New York, New York

    Departments of Neurology and Anesthesiology, Albert Einstein College of Medicine, Bronx, New York
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  • Nathaniel Katz
    Affiliations
    Analgesic Solutions, Natick, Massachusetts

    Tufts University School of Medicine, Boston, Massachusetts
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  • Russell K. Portenoy
    Affiliations
    Department of Pain Medicine and Palliative Care, Beth Israel Medical Center, New York, New York

    Departments of Neurology and Anesthesiology, Albert Einstein College of Medicine, Bronx, New York
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      Abstract

      Dose selection of a once-daily, osmotic-controlled extended-release (ER) hydromorphone assumes that this drug and immediate-release (IR) hydromorphone are dose equivalent. This trial evaluated dose equivalence using a measure of assay sensitivity. Patients were converted to open-label IR hydromorphone, underwent dose titration, and those on a satisfactory dose entered a randomized, double-blind phase receiving 7 days of: 1) hydromorphone IR 5 times/day at approximately this dose; 2) once-daily hydromorphone ER at this dose; or 3) once-daily hydromorphone ER at one-half this dose. Efficacy was measured using breakthrough medication use, pain, sleep, and global assessments. Of 148 patients, 113 (76%) were randomized. IR and full-dose ER groups produced comparable effects on all measures. Although the prespecified primary analysis of the difference in total daily dose of breakthrough medication between the full-dose ER and half-dose ER groups was not significant, more patients in the half-dose ER group required an increase in breakthrough medication (P = .026) and the half-dose ER group both increased the number of breakthrough doses (P = .026) and had greater percent change in the total daily dose of breakthrough medication (P = .037) than the full-dose group, suggesting that switching from IR to ER hydromorphone at the same daily dose provides equivalent analgesia.

      Perspective

      In a randomized, double-blind trial, the same total daily dose of immediate-release hydromorphone and once-daily osmotic-controlled extended-release hydromorphone had comparable effects. Detection of different effects between blinded dose levels was used as a measure of assay sensitivity. The measure of assay sensitivity can enhance the interpretation of dose equivalence or noninferiority trials.

      Key words

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