Analgesic Efficacy and Tolerability of Intravenous Morphine Versus Combined Intravenous Morphine and Oxycodone in a 2-Center, Randomized, Double-Blind, Pilot Trial of Patients With Moderate to Severe Pain After Total Hip Replacement Robin Joppich, MD 1, *; Patricia Richards, MD, PhD 2, *; Robin Kelen, MS, RN 2 ; Warren Stern, PhD 2 ; Kourosh Zarghooni, MD 4 ; Christina Otto, MD 4,† ; Andreas Böhmer, MD 1,† ; Frank Petzke, MD 5 ; Tilman Treptau, PhD 6 ; Rolf Lefering, PhD 6 ; Holger Bäthis, MD 3 ; and Edmund Neugebauer, MD, PhD 6 1 Department of Anaesthesia/Operative Intensive Care, Witten/Herdecke University, Cologne, Germany; 2 QRxPharma, Inc, Bedminster, New Jersey; 3 Department of Trauma/Orthopaedic Surgery, Witten/Herdecke University, Cologne, Germany; 4 Department of Orthopaedic and Trauma Surgery, ZKS, University of Cologne, Cologne, Germany; 5 Department of Anaesthesiology and Postoperative Intensive Care, University of Cologne, Cologne, Germany; and 6 Institute for Research in Operative Medicine, Witten/Herdecke University, Cologne, Germany ABSTRACT Background: Results from studies with a combina- tion of oral morphine and oxycodone in postsurgical patients demonstrate significant analgesia and a toler- ability profile comparable to other pain medications at morphine-equivalent doses. However, an intravenous (IV) combination has not previously been studied. Objective: This study evaluated the efficacy and tol- erability of IV morphine versus a combination of IV morphine and IV oxycodone in a 1:1 ratio. Methods: This was a 2-center, randomized, double- blind, active-controlled pilot trial of 40 patients who had undergone total hip replacement. After surgery, when pain levels reached 4 (on the 11-point Numerical Pain Rating Scale), patients were randomized to 1 of 2 treat- ment groups. In part 1 of the study, patients were dosed every 5 minutes for the first 65 minutes (up to 13 doses) with study drug, provided that vital signs criteria were met. After an initial loading dose of either morphine 1.5 mg coadministered with oxycodone 1.5 mg or morphine 3 mg alone, patients received IV morphine 1.5 mg or IV morphine 0.75 mg/IV oxycodone 0.75 mg every 5 min- utes. If patients achieved a pain score of 2 or experienced intolerable adverse events to drug when stable, they were permitted to enter part 2. In part 2, patients received blinded study medication (IV morphine plus IV oxy- codone [0.5 mg/0.5 mg] or 1 mg IV morphine alone) via patient-controlled analgesia (PCA) for 47 hours. Results: At baseline, treatment groups were compa- rable except for a higher proportion of females in the IV morphine group. Baseline pain intensity averaged 7 on the Numerical Pain Rating Scale of 0 to 10. One patient in the morphine group and 2 patients in the morphine/oxycodone group discontinued the study. The sum of the pain intensity differences from baseline to 65 minutes during the dose-titration phase was 1.8 for morphine alone versus 2.7 for morphine/oxy- codone (P = 0.12); these values occurred at the same median number of doses (12) for each group. In part 2 (PCA dosing) of the study, similar levels of analgesia were achieved. During the study, 24% of the IV mor- phine/oxycodone group and 37% of the IV morphine group experienced nausea, and 10% of the IV mor- phine/oxycodone group and 16% of the IV morphine group had emesis. Two patients in the IV morphine/ oxycodone group and 4 in the IV morphine alone group experienced oxygen desaturation. *These authors contributed equally to this work. † Dual Opioid Study Group: Thomas Kaulhausen, Nicolas Knobbe, Peter Knöll, Ulrich Limper, Martin Lützerath, Annika Sayar, Jan Siewe, Stefan Wegener, Gabriele Werner, and Ayla Yagdiran. Accepted for publication June 22, 2012. http://dx.doi.org/10.1016/j.clinthera.2012.06.023 0149-2918/$ - see front matter © 2012 Elsevier HS Journals, Inc. All rights reserved. Clinical Therapeutics/Volume 34, Number 8, 2012 August 2012 1751