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.
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.
Langford
Richard M
RM
Pain and Anaesthesia Research Group, St Bartholomew's Hospital, West Smithfield, London, EC1A 7BE, UK. r.m.langforf@qmul.ac.uk
Joshi
Girish P
GP
Gan
Tong J
TJ
Mattera
Maria Stoeckl
MS
Chen
Wen-Hung
WH
Revicki
Dennis A
DA
Chen
Connie
C
Zlateva
Gergana
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D001291:Attitude of Health Personnel; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D017558:Elective Surgical Procedures / Q000009:adverse effects; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy*; D017060:Patient Satisfaction; D010919:Placebos; D011594:Psychometrics / Q000379:methods; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects*; D000096926:Benzenesulfonamides
D000701:Analgesics, Opioid; D016861:Cyclooxygenase Inhibitors; D007555:Isoxazoles; D010919:Placebos; D013449:Sulfonamides; C406224:valdecoxib; D000096926:Benzenesulfonamides; C409945:parecoxib