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Reduction in Opioid-Related Adverse Events and Improvement in Function with Parecoxib followed by Valdecoxib Treatment after Non-Cardiac Surgery

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial

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Abstract

Background: Multimodal pain therapy including cyclo-oxygenase-2 inhibitors can result in optimal pain management with decreased opioid use and fewer opioid-related adverse events. Patient reported outcomes (PROs) help identify benefits in reduced opioid use and increased pain control.

Methods: In this randomized, double-blind trial, patients (n=1062) undergoing major non-cardiac elective surgery received either parenteral parecoxib for 3 days or placebo then oral valdecoxib or placebo for a total of 10 days, with both arms being allowed additional opioid analgesia. Clinically meaningful opioid-related adverse events were assessed daily using the Opioid-Related Symptom Distress Scale (OR-SDS). Pain severity and interference with function were evaluated daily using the modified Brief Pain Inventory exploratory form (mBPI-e). Additional validation work was undertaken to understand the psychometric properties of the two PROs. Detailed clinical results were reported elsewhere.

Results: Patients receiving parecoxib/valdecoxib achieved significantly better pain control and consumed 37% and 28% less opioid medication than the placebo group on day 2 and day 3, respectively. Over the 10-day treatment period, patients receiving parecoxib/valdecoxib consumed 31% less opioid medication. This coincided with significantly fewer (p < 0.0001) OR-SDS clinically meaningful events (CMEs) and lower mBPI-e scores from days 2–10 in the parecoxib/valdecoxib group compared with the placebo group. On day 3, the percentage of patients reporting one, two or three CMEs in the parecoxib/valdecoxib versus placebo group was 11.6% versus 13.0%, 2.3% versus 5.1%, and 0.8% versus 2.3%, respectively. The mean (± standard error) mBPI-e pain severity scores over days 2–10 were 2.47 ± 0.04 for the parecoxib/valdecoxib group and 3.01 ±0.04 for the placebo group, and the mean mBPI-e pain interference scores were 1.73±0.04 and 2.19 ± 0.04, respectively.

Conclusions: Patients receiving parecoxib/valdecoxib had less pain interference on physical functioning, required less opioid medication and experienced fewer clinically meaningful opioid-related adverse events than patients receiving placebo.

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References

  1. Wheeler M, Oderda GM, Ashburn MA, et al. Adverse events associated with postoperative opioid analgesia: a systematic review. J Pain 2002 Jun; 3(3): 159–80

    Article  PubMed  Google Scholar 

  2. Stephens J, Laskin B, Pashos C, et al. The burden of acute postoperative pain and the potential role of the COX-2-specific inhibitors. Rheumatology (Oxford) 2003 Nov; 42Suppl. 3: iii40–52

    CAS  Google Scholar 

  3. Joshi GP. Multimodal analgesia techniques and postoperative rehabilitation. Anesthesiol Clin North America 2005 Mar; 23(1): 185–202

    Article  PubMed  CAS  Google Scholar 

  4. White PF. The changing role of non-opioid analgesic techniques in the management of postoperative pain. Anesth Analg 2005 Nov; 101(5 Suppl.): S5–22

    Article  PubMed  Google Scholar 

  5. Ketorolac. Summary of product characteristics. EMC Medicines; 2008 [online]. Available from URL: http://emc.medi cines.org.uk/emc/assets/c/html/displaydoc.asp?documentid= 1737 [Accessed 2008 Apr]

  6. Macario A, Lipman AG. Ketorolac in the era of cyclooxygenase-2 selective nonsteroidal anti-inflammatory drugs: a systematic review of efficacy, side effects, and regulatory issues. Pain Med 2001 Dec; 2(4): 336–51

    Article  PubMed  CAS  Google Scholar 

  7. Noveck RJ, Hubbard RC. Parecoxib sodium, an injectable COX-2-specific inhibitor, does not affect unfractionated heparin-regulated blood coagulation parameters. J Clin Pharmacol 2004 May; 44(5): 474–80

    Article  PubMed  CAS  Google Scholar 

  8. Peura DA. Gastrointestinal safety and tolerability of non-selective nonsteroidal anti-inflammatory agents and cyclo-oxygenase-2-selective inhibitors. Cleve Clin J Med 2002; 69Suppl. 1: SI31–9

    Article  PubMed  Google Scholar 

  9. Cheer SM, Goa KL. Parecoxib (parecoxib sodium). Drugs 2001; 61(8): 1133–141; discussion 42-3

    Article  PubMed  CAS  Google Scholar 

  10. Hubbard RC, Naumann TM, Traylor L, et al. Parecoxib sodium has opioid-sparing effects in patients undergoing total knee arthroplasty under spinal anaesthesia. Br J Anaesth 2003 Feb; 90(2): 166–72

    Article  PubMed  CAS  Google Scholar 

  11. Camu F, Beecher T, Recker DP, et al. Valdecoxib, a COX-2-specific inhibitor, is an efficacious, opioid-sparing analgesic in patients undergoing hip arthroplasty. Am J Ther 2002 Jan–Feb; 9(1): 43–51

    Article  PubMed  Google Scholar 

  12. Gan TJ, Joshi GP, Viscusi E, et al. Preoperative parenteral parecoxib and follow-up oral valdecoxib reduce length of stay and improve quality of patient recovery after laparoscopic cholecystectomy surgery. Anesth Analg 2004 Jun; 98(6): 1665–173, table of contents

    Article  PubMed  CAS  Google Scholar 

  13. Joshi GP, Viscusi ER, Gan TJ, et al. Effective treatment of laparoscopic cholecystectomy pain with intravenous followed by oral COX-2 specific inhibitor. Anesth Analg 2004 Feb; 98(2): 336–42

    Article  PubMed  CAS  Google Scholar 

  14. Malan Jr TP, Marsh G, Hakki SI, et al. Parecoxib sodium, a parenteral cyclooxygenase 2 selective inhibitor, improves morphine analgesia and is opioid-sparing following total hip arthroplasty. Anesthesiology 2003 Apr; 98(4): 950–6

    Article  PubMed  CAS  Google Scholar 

  15. Reynolds LW, Hoo RK, Brill RJ, et al. The COX-2 specific inhibitor, valdecoxib, is an effective, opioid-sparing analgesic in patients undergoing total knee arthroplasty. J Pain Symptom Manage 2003 Feb; 25(2): 133–41

    Article  PubMed  CAS  Google Scholar 

  16. Barton SF, Langeland FF, Snabes MC, et al. Efficacy and safety of intravenous parecoxib sodium in relieving acute postoperative pain following gynecologic laparotomy surgery. Anesthesiology 2002 Aug; 97(2): 306–14

    Article  PubMed  CAS  Google Scholar 

  17. Bikhazi GB, Snabes MC, Bajwa ZH, et al. A clinical trial demonstrates the analgesic activity of intravenous parecoxib sodium compared with ketorolac or morphine after gynecologic surgery with laparotomy. Am J Obstet Gynecol 2004 Oct; 191(4): 1183–91

    Article  PubMed  CAS  Google Scholar 

  18. Rasmussen GL, Steckner K, Hogue C, et al. Intravenous parecoxib sodium for acute pain after orthopedic knee surgery. Am J Orthop 2002 Jun; 31(6): 336–43

    PubMed  Google Scholar 

  19. Noveck RJ, Laurent A, Kuss M, et al. Parecoxib sodium does not impair platelet function in healthy elderly and non-elderly individuals: two randomised, controlled trials. Clin Drug Invest 2001; 21(7): 465–76

    Article  CAS  Google Scholar 

  20. Nussmeier NA, Whelton AA, Brown MT, et al. Safety and efficacy of the cyclooxygenase-2 inhibitors parecoxib and valdecoxib after noncardiac surgery. Anesthesiology 2006 Mar; 104(3): 518–26

    Article  PubMed  CAS  Google Scholar 

  21. Keats AS. The ASA classification of physical status: a recapitulation. Anesthesiology 1978 Oct; 49(4): 233–6

    Article  PubMed  CAS  Google Scholar 

  22. Twycross R. Opioids. In: Melzak R, Wall PD, editors. Textbook of pain. 4th ed. New York: Churchill Livingstone, 1999: 1202

    Google Scholar 

  23. Apfelbaum JL, Gan TJ, Zhao S, et al. Reliability and validity of the perioperative opioid-related symptom distress scale. Anesth Analg 2004 Sep; 99(3): 699–709

    Article  PubMed  CAS  Google Scholar 

  24. Chan K, Chen W, Gan T, et al. Development and validity of a composite clinically meaningful events (CMEs) score based on the opioid-related symptom distress scale (OR-SDS) [poster no. 880]. Presented at the American Pain Society Annual Meeting; 2007 May 2–5; Washington, DC

  25. Chen W, Chan K, Gan T, et al. Development and validation of the modified Brief Pain Inventory short form (mBPI-sf) in CABG and general surgery patients [poster no. 889]. Presented at the American Pain Society Annual Meeting; 2007 May 2–5; Washington, DC

  26. Cleeland C. Research in cancer pain. What we know and what we need to know. Cancer 1991 Feb 1; 67(3 Suppl.): 823–7

    Article  PubMed  CAS  Google Scholar 

  27. Mendoza TR, Chen C, Brugger A, et al. The utility and validity of the Modified Brief Pain Inventory in a multipledose postoperative analgesic trial. Clin J Pain 2004 Sep–Oct; 20(5): 357–62

    Article  PubMed  Google Scholar 

  28. Nussmeier NA, Whelton AA, Brown MT, et al. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. NEngl J Med 2005 Mar 17; 352(11): 1081–91

    Article  CAS  Google Scholar 

  29. Ott E, Nussmeier NA, Duke PC, et al. Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surg 2003 Jun; 125(6): 1481–92

    Article  PubMed  CAS  Google Scholar 

  30. Borgdorff P, Tangelder GJ, Paulus WJ. Cyclooxygenase-2 inhibitors enhance shear stress-induced platelet aggregation. J Am Coll Cardiol 2006 Aug 15; 48(4): 817–23

    Article  PubMed  CAS  Google Scholar 

  31. Gan TJ, Joshi GP, Zhao SZ, et al. Presurgical intravenous parecoxib sodium and follow-up oral valdecoxib for pain management after laparoscopic cholecystectomy surgery reduces opioid requirements and opioid-related adverse effects. Acta Anaesthesiol Scand 2004 Oct; 48(9): 1194–207

    Article  PubMed  CAS  Google Scholar 

  32. Prospect Working Group. Procedure-specific evidence-based recommendations for the management of postoperative pain, 2008 [online]. Available from URL: http://www.postoppain.org [Accessed 2008 Apr]

  33. Stubhaug A, Grimstad J, Breivik H. Lack of analgesic effect of 50 and 100 mg oral tramadol after orthopaedic surgery: a randomized, double-blind, placebo and standard active drug comparison. Pain 1995 Jul; 62(1): 111–18

    Article  PubMed  CAS  Google Scholar 

  34. Tarradell R, Pol O, Farre M, et al. Respiratory and analgesic effects of meperidine and tramadol in patients undergoing orthopedic surgery. Methods Find Exp Clin Pharmacol 1996 Apr; 18(3): 211–8

    PubMed  CAS  Google Scholar 

  35. Ferraz AA, Cowles VE, Condon RE, et al. Nonopioid analgesics shorten the duration of postoperative ileus. Am Surg 1995 Dec; 61(12): 1079–83

    PubMed  CAS  Google Scholar 

  36. Daniels SE, Grossman EH, Kuss ME, et al. A double-blind, randomized comparison of intramuscularly and intravenously administered parecoxib sodium versus ketorolac and placebo in a post-oral surgery pain model. Clin Ther 2001 Jul; 23(7): 1018–31

    Article  PubMed  CAS  Google Scholar 

  37. Ng A, Smith G, Davidson AC. Analgesic effects of parecoxib following total abdominal hysterectomy. Br J Anaesth 2003 Jun; 90(6): 746–9

    Article  PubMed  CAS  Google Scholar 

  38. Malan Jr TP, Gordon S, Hubbard R, et al. The cyclooxy-genase-2-specific inhibitor parecoxib sodium is as effective as 12 mg of morphine administered intramuscularly for treating pain after gynecologic laparotomy surgery. Anesth Analg 2005 Feb; 100(2): 454–60

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This study was sponsored by Pfizer Inc., New York, NY, USA. The authors would like to thank Raymond Cheung from Pfizer for his detailed review and input. Girish P. Joshi received research grants and honoraria from Pfizer. Connie Chen and Gergana Zlateva are employees and own stock in Pfizer Inc. The other authors have no conflicts of interest that are directly relevant to the content of this study. Editorial support was provided by R. Passmore, PhD, of PAREXEL, and was funded by Pfizer Inc.

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Authors and Affiliations

  1. Pain and Anaesthesia Research Centre, St Bartholomew’s Hospital, West Smithfield, London, EC1A 7BE, UK

    Richard M. Langford

  2. Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Girish P. Joshi

  3. Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, USA

    Tong J. Gan

  4. Center for Health Outcomes Research, United BioSource Corporation, Bethesda, Maryland, USA

    Maria Stoeckl Mattera, Wen-Hung Chen & Dennis A. Revicki

  5. Pfizer Inc., New York, New York, USA

    Connie Chen & Gergana Zlateva

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  1. Richard M. Langford
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  2. Girish P. Joshi
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Correspondence to Richard M. Langford.

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Langford, R.M., Joshi, G.P., Gan, T.J. et al. Reduction in Opioid-Related Adverse Events and Improvement in Function with Parecoxib followed by Valdecoxib Treatment after Non-Cardiac Surgery. Clin. Drug Investig. 29, 577–590 (2009). https://doi.org/10.2165/11317570-000000000-00000

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