Postoperative intravenous parecoxib sodium followed by oral celecoxib post total knee arthroplasty in osteoarthritis patients (PIPFORCE): a multicentre, double-blind, randomised, placebo-controlled trial

Abstract

ObjectivesTo evaluate the morphine-sparing effects of the sequential treatment versus placebo in subjects undergoing total knee arthroplasty (TKA), the effects on pain relief, inflammation control and functional rehabilitation after TKA and safety.DesignDouble-blind, pragmatic, randomised, placebo-controlled trial.SettingFour tertiary hospitals in China.Participants246 consecutive patients who underwent elective unilateral TKA because of osteoarthritis (OA).InterventionsPatients were randomised 1:1 to the parecoxib/celecoxib group or the control group. The patients in the parecoxib/celecoxib group were supplied sequential treatment with intravenous parecoxib 40 mg (every 12 hours) for the first 3 days after surgery, followed by oral celecoxib 200 mg (every 12 hours) for up to 6 weeks. The patients in the control group were supplied with the corresponding placebo under the same instructions.Primary and secondary outcome measuresThe primary endpoint was the cumulative opioid consumption at 2 weeks post operation (intention-to-treat analysis). Secondary endpoints included the Knee Society Score, patient-reported outcomes and the cumulative opioid consumption.ResultsThe cumulative opioid consumption at 2 weeks was significantly smaller in the parecoxib/celecoxib group than in the control group (median difference, 57.31 (95% CI 34.66 to 110.33)). The parecoxib/celecoxib group achieving superior Knee Society Scores and EQ-5D scores and greater Visual Analogue Scale score reduction during 6 weeks. Interleukin 6, erythrocyte sedation rate and C-reactive protein levels were reduced at 72 hours, 2 weeks and 4 weeks and prostaglandin E2 levels were reduced at 48 hours and 72 hours in the parecoxib/celecoxib group compared with the placebo group. The occurrence of adverse events (AEs) was significantly lower in the parecoxib/celecoxib group.ConclusionsThe sequential intravenous parecoxib followed by oral celecoxib regimen reduces morphine consumption, achieves better pain control and functional recovery and leads to less AEs than placebo after TKA for OA.Trial registration numberClinicalTrials.gov (ID:NCT02198924).

An opioid-sparing protocol with intravenous parecoxib can effectively reduce morphine consumption after simultaneous bilateral total knee arthroplasty

“…The MME was not significantly different in the two Bain groups with parecoxib vs. placebo (48.86 vs. 51.33 mg, respectively 18 . In two other RCTs comparing multiple doses of parecoxib versus placebo, the opioid-sparing effects appeared to be significant 16 , 20 . Hubbard observed a dose-dependent opioid-sparing effect of parecoxib after TKA as the MME decreased from approximately 60 mg in the placebo group to approximately 40 mg in the parecoxib group, at postoperative 48 hours 20 .…”

“…The efficacy of parecoxib for pain relief after total joint arthroplasty has been validated in several studies 16 – 20 . The efficacy of each multimodal pain management protocol can be difficult to assess.…”

“…Although it has been validated that pain intensity following SBTKA and unilateral TKA procedures are similar, the narcotics required to relieve the pain during the perioperative period can be 20% higher in patients that underwent SBTKA 15 . Current studies regarding opioid-sparing protocols consisting of intravenous parecoxib assessed patients that had undergone a unilateral TKA procedure 16 – 19 . As anticipated, intravenous parecoxib was associated with lower pain scores in the postoperative period, compared with the placebo group 16 – 18 .…”

“…Current studies regarding opioid-sparing protocols consisting of intravenous parecoxib assessed patients that had undergone a unilateral TKA procedure 16 – 19 . As anticipated, intravenous parecoxib was associated with lower pain scores in the postoperative period, compared with the placebo group 16 – 18 . However, the postoperative cumulative opioid doses in the parecoxib group were relatively higher (28.93–48.86 mg) at postoperative 72 h 16 , 18 , 20 , which did not meet the expectation of an “opioid-sparing” effect.…”

The antifibrinolytic and anti‐inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty patients: a randomized controlled trial

“…Patients were offered the usual standardized anesthesia, consisting of periarticular injection of ropivacaine (0.2%) perioperatively and oral administration of celecoxib (200 mg twice daily; Pfizer, New York, USA) and enteric‐coated diclofenac sodium (50 mg twice daily; Novartis, Basel, Switzerland) at the same time (i.e. 8:00 a.m. and 5:00 p.m.) postoperatively during hospitalization .…”