Efficacy and Safety of Postoperative Intravenous Parecoxib Sodium Followed by Oral Celecoxib in Osteoarthritis Patients
Condition: Pain; Inflammation
MeSH terms: Osteoarthritis; Inflammation
Study type: Interventional
Phase: Phase 4

Summary: 
      In mainland China, knee Osteoarthritis (OA) is the leading cause of disability in older
      persons. Total knee arthroplasty (TKA) is now generally regarded by orthopaedic surgeons and
      patients as an effective treatment for end-stage knee OA in order to relieve pain, correct
      joint deformity and improve the life quality of patients.However, TKA has been called as one
      of the most painful Orthopedics surgery due to the weight bearing characteristics of knee
      joint and the high demand of functional exercise within the 6-8 weeks post operation. The
      targeted application of selective cyclooxygenase (COX) -2 inhibitor, such as Parecoxib or
      Celecoxib, can significantly reduce the level of inflammatory reaction one and two days
      postoperation . In addition, the perioperative administration of Celecoxib can directly or
      indirectly relieve postoperative pain, improve articular function and eventually augment life
      quality of the patients . Recently, effective treatment of post-operative pain with
      intravenous followed by oral COX-2 specific inhibitor has been demonstrated in many
      post-operative pain models . Significant morphine sparing effect and reduction of opioid
      distressed symptoms were also observed. In China, many surgeons have accept it as a routine
      strategy for controlling pain post TKA to sequentially give parecoxib 40 mg intravenously
      twice daily for the first 3 days post surgery and then Celecoxib 200mg orally twice daily.
      Although satisfactory results of this combination treatment on short-term pain reduction and
      functional improvement has been observed in clinical practice, high quality evidence is still
      lacking to prove its effect on the medium or long-term functionality recovery. This study is
      being conducted to investigate the combination regimen with intravenous parecoxib followed by
      oral celecoxib for post-surgical analgesic treatment in osteoarthritis patients undergoing
      total knee arthroplastic (TKA) surgery. Subjects will receive double-blinded study medication
      consisting of parecoxib injection in analgesic doses or matching placebo followed by oral
      celecoxib in acute pain doses or matching placebo in a double-blinded fashion. The hypothesis
      is subjects treated with parecoxib/celecoxib will consume less morphine over the first 24
      hours of postoperation period, achieve improved pain control over study period, a quicker
      return to functionality, and has less opioid adverse events than those treated with opioids
      alone over 6-week recovery phase.
    

Detailed description: 
      Total knee arthroplasty (TKA), though generally regarded as an effective treatment for
      end-stage knee OA, has been called as "one of the most painful orthopedics surgeries" due to
      the weight bearing characteristics of knee joint and the high demand of functional exercise
      within the 6-8 weeks post operation.

      Parecoxib and Celecoxib have been found to be able to relieve postoperative pain, spare
      opioid use, improve articular function and eventually augment life quality of the patients
      after TKA. In China, therefore, many surgeons have accept it as a routine strategy for
      controlling pain post TKA to sequentially use Parecoxib and then Celecoxib. However, high
      quality evidence is still lacking to prove its effect on the medium or long-term
      functionality recovery.

      This multicenter, double blind, parallel-group randomized study, therefore, is aiming to
      evaluate efficacy and safety of postoperative intravenous Parecoxib sodium followed by oral
      Celecoxib in OA patients undergoing TKA. The hypothesis is that compared to placebo with
      opioids as rescue treatment, sequential use of Parecoxib/Celecoxib can achieve not only less
      morphine consumption over postoperatively 2 weeks, but also better pain control, quicker
      functional recovery, and less opioid related adverse events over 6-week recovery phase.

      The primary objective of this study is to evaluate the morphine-sparing effects of the
      combination treatment with Parecoxib and Celecoxib versus placebo in subjects undergoing TKA.
      The secondary objective is to compare the effects of the combination treatment versus placebo
      on pain relief, inflammation control and functional rehabilitation after TKA. Total 86
      subjects per group would have 90% power in detecting 100 mg or more in mean difference of
      morphine use on Day 14 between the two groups, assuming a common standard deviation of 200,
      and a two-sided alpha level of 0.05. This would result in a total 172 subjects. In
      consideration of 30% drop outs, 246 subjects would be adequate for the study. All subjects
      who meet the study inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio
      to either Parecoxib/Celecoxib group or placebo group. The allocation or randomization will be
      study site based.Data will be collected using an Electronic Data Capture (EDC) under a strict
      intent-to-treat methodology, i.e., all the data of any Inform Consent Form signed subjects
      will be included in the study database.All subjects will be recruited from 4 study centers in
      China. The study will consist of 3 phases: an initial screening phase which must be completed
      within 30 days prior to randomization; a 6-week double blind treatment phase; and a 6 week
      follow up phase. A two-week wash-out procedure will be required before randomization for the
      patients with previous use of nonsteroidal antiinflammatory drug (NSAID) or COX-2 specific
      inhibitors.Variables considered continuous will be presented by descriptive statistics:
      number, mean, standard deviation, median, minimum, and maximum; and analyzed using parametric
      or non-parametric ANOVA, as appropriate. Variables considered categorical will be tabulated
      by frequency counts and percentages; and analyzed using Chi-square test or Fisher's exact
      tests. All the statistical tests will be two-sided with alpha=0.05, i.e., a p value <= 0.05
      would be considered statistically significant.
    

Intervention name(s): Parecoxib and Celecoxib; placebo
Intervention type(s): Drug; Drug
Intervention description(s): Patients in the study group are supplied sequential treatment with Parecoxib 40 mg intravenously (IV) twice daily (Q12h) for the first 3 days post-surgery followed by Celecoxib 200mg orally twice daily (Q12h) up to 6 weeks post-surgery.; control patients are supplied with the corresponding placebo with the same instructions.
Intervention MeSH terms: Celecoxib; Parecoxib
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: sequential administration; pain control; inflammation control; function recovery