Efficacy and Safety of Postoperative Intravenous Parecoxib Sodium Followed by Oral Celecoxib in Osteoarthritis Patients

• Status: Completed
• Trial end date: 2016-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Peking Union Medical College Hospital
• Treatments: Celecoxib; Parecoxib; Tramadol

Criteria

Inclusion Criteria:

1. The subject is scheduled to undergo elective unilateral total knee arthroplasty because of OA, performed under a standardized regimen of 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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