Efficacy and Safety of Postoperative Intravenous Parecoxib Sodium Followed by Oral Celecoxib in Osteoarthritis Patients
Information source: Peking Union Medical College Hospital
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pain; Inflammation
Intervention: Parecoxib and Celecoxib (Drug); placebo (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Peking Union Medical College Hospital Official(s) and/or principal investigator(s): Xisheng Weng, M.D., Principal Investigator, Affiliation: Peking Union Medical College Hospital
Overall contact: Xisheng Weng, M.D., Phone: 0+8613366200018, Email: xshweng@medmail.com.cn
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.
Clinical Details
Official title: A Study to Evaluate Efficacy and Safety of Postoperative Intravenous Parecoxib Sodium Followed by Oral Celecoxib Post Total Knee Arthroplasty in Osteoarthritis Patients
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Total narcotic use
Secondary outcome: Knee Society ScoreWestern Ontario and McMaster Universities Arthritis(WOMAC) Index Knee Society Score Total Morphine use Total narcotic use Visual Analogue Scale EuroQol (EQ-5D) Score
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 90 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. The subject is scheduled to undergo elective unilateral total knee arthroplasty
because of OA, performed under a standardized regimen of spinal or general
anesthesia, as specified in this protocol.
2. Evidence of a personally signed and dated informed consent document indicating that
the subject has been informed of all pertinent aspects of the study.
3. The subject is a male or female over 18 years of age.
4. Subjects of childbearing potential must agree to use an effective method of
contraception throughout the study and for 42 days after the last dose of assigned
treatment.
5. Total duration of the surgical procedure is four hours or less.
6. ASA grade 1-3 subjects.
7. Subjects who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, standardized rehabilitation scheme, and other study procedures.
8. The subject is in satisfactory health as determined by the investigator on the basis
of medical history and physical exam.
9. The subject must demonstrate sufficient psychomotor dexterity and cognitive capacity
to use intravenous (IV) patient-controlled analgesia(PCA).
10. The subject who live near to the hospital may be considered prior for the concern of
convenient and sufficient follow-up.
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Exclusion Criteria:
1. The subject requires a revision to previous knee arthroplasty and/or is having a
bilateral knee arthroplasties.
2. The subject requires an emergency knee arthroplasty.
3. Subject uses opioids more than three days/ week prior to operation unless they
discontinue the opioids two months prior to screen.
4. Subject has a known hypersensitivity to COX-2 specific inhibitors, sulfonamides,
lactose, NSAIDs, opioids or acetaminophen/paracetamol.
5. The subject has a history of arthritis:, chronic pain, metastasis, and Paget's
disease.
6. The subject received any investigational medication within 30 days prior to the first
dose of study medication.
7. The subject has any known laboratory abnormality, which in the opinion of the
investigator, would contraindicate study participation ≧1. 5 times the upper limit of
the normal reference range.
8. The subject has an active malignancy of any type, or history of a malignancy
(Subjects who have a history of basal cell carcinoma that has been successfully
treated can be entered into the study.
9. Subject had any condition, which could preclude use of NSAIDs or COX-2 specific
inhibitors.
10. The subject has active or suspected esophageal, gastric, pyloric channel, or duodenal
ulceration history.
11. The subject has received warfarin or other anticoagulants during the 30 days
preceding the first dose of study medication.
12. Subject is anticipated to require or requires treatment with lithium.
13. Subject is American Society of Anesthesiologists(ASA) grade 4-5.
14. The subject has a history of a psychiatric disorder requiring new or changing
treatment
15. The subject has a history of uncontrolled chronic disease or a concurrent clinically
significant illness, medical condition.
16. The subject has any cognitive impairment or other characteristics that would in the
investigator's opinion preclude study participation or compliance with protocol
mandated procedures.
17. Subject has a history of asthma or bronchospasm, which requires treatment with
glucocorticoids.
18. Subject had a history of alcohol, analgesic or narcotic abuse.
19. Subject has been previously randomized into the study
20. Subjects who are investigational site staff members or relatives of those site staff
21. Participation in other studies within 3 months before the current study begins and/or
during study participation
22. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation.
23. Pregnant females, breastfeeding females, or males and females of childbearing
potential not using effective contraception.
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Locations and Contacts
Xisheng Weng, M.D., Phone: 0+8613366200018, Email: xshweng@medmail.com.cn
Peking Union Medical College Hospital, Beijing 100730, China; Recruiting weng xi sheng, doctor, Phone: 0+8613366200018, Email: xshweng@medmail.com.cn Xisheng Weng, M.D., Principal Investigator
Additional Information
Related publications: Carr AJ, Robertsson O, Graves S, Price AJ, Arden NK, Judge A, Beard DJ. Knee replacement. Lancet. 2012 Apr 7;379(9823):1331-40. doi: 10.1016/S0140-6736(11)60752-6. Epub 2012 Mar 6. Review. Du Q, Ge HJ, Zhu PF. Effects of perioperative analgesia on postoperative inflammatory response. Int J Anesth Resus., 2007, 28(1):48-53. Holm B, Kristensen MT, Bencke J, Husted H, Kehlet H, Bandholm T. Loss of knee-extension strength is related to knee swelling after total knee arthroplasty. Arch Phys Med Rehabil. 2010 Nov;91(11):1770-6. doi: 10.1016/j.apmr.2010.07.229. Honsawek S, Deepaisarnsakul B, Tanavalee A, Sakdinakiattikoon M, Ngarmukos S, Preativatanyou K, Bumrungpanichthaworn P. Relationship of serum IL-6, C-reactive protein, erythrocyte sedimentation rate, and knee skin temperature after total knee arthroplasty: a prospective study. Int Orthop. 2011 Jan;35(1):31-5. doi: 10.1007/s00264-010-0973-0. Epub 2010 Feb 21. Erratum in: Int Orthop. 2011 Nov;35(11):1749. Rasmussen GL, Steckner K, Hogue C, Torri S, Hubbard RC. Intravenous parecoxib sodium foracute pain after orthopedic knee surgery. Am J Orthop (Belle Mead NJ). 2002 Jun;31(6):336-43. Hubbard RC, Naumann TM, Traylor L, Dhadda S. Parecoxib sodium has opioid-sparing effects in patients undergoing total knee arthroplasty under spinal anaesthesia. Br J Anaesth. 2003 Feb;90(2):166-72. Nussmeier NA, Whelton AA, Brown MT, Joshi GP, Langford RM, Singla NK, Boye ME, Verburg KM. Safety and efficacy of the cyclooxygenase-2 inhibitors parecoxib and valdecoxib after noncardiac surgery. Anesthesiology. 2006 Mar;104(3):518-26.
Starting date: December 2013
Last updated: July 21, 2014
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