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

NCT02198924 | Completed Phase 4 DMC

• 1 other identifier: WI1180091
• Study Type: interventional
• Target: 246
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pain; Inflammation

Keywords

sequential administration; pain control; inflammation control; function recovery

Outcome Measures

Primary Outcomes (1)

• Total narcotic use

  The sum of the cumulative Morphine consumption over the first 24 hours postsurgical period and the narcotic drug consumption till 72h, 2w post operation will be converted to morphine equivalents. The converting of tramadol to Morphine equivalents is estimated as 150mg Tramadol equals to 10mg of Morphine injection.

  Post-operative 2 WEEKS

Secondary Outcomes (7)

• Knee Society Score

  post-operation 6 weeks

• Western Ontario and McMaster Universities Arthritis(WOMAC) Index

  prior to operation and at 2w,4w and 6w post operation

• Knee Society Score

  prior to operation and at 2w and 4w post operation

• Total Morphine use

  over the first 24 hours postsurgical period

• Total narcotic use

  72h, 4w, 6w post operation

Other Outcomes (19)

• Knee circumference

  prior to operation and at 72h, 2w, 4w and 6w post operation

• skin temperature

  prior to operation and at 72h, 2w, 4w and 6w post operation

• Erythrocyte sedimentation rate(ESR)

  prior to operation and at 72h, 2w, 4w and 6w post operation

Study Arms (2)

Parecoxib and Celecoxib

EXPERIMENTAL

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. Patient-controlled intravenous analgesia (PCIA) with Morphine is administrated to all the subjects starting immediately post-anesthesia and ending at 24h after operation. As long as oral intake is feasible, both the two groups may receive centrally-acting analgesic Tramadol Hydrochloride Sustained release tablets (TRAMCONTIN) as rescue analgesia if VAS score≧3.

Drug: Parecoxib and Celecoxib

placebo

PLACEBO COMPARATOR

Patients in the control group are supplied with the corresponding placebo with the same instructions. Patient-controlled intravenous analgesia (PCIA) with Morphine is administrated to all the subjects starting immediately post-anesthesia and ending at 24h after operation. As long as oral intake is feasible, both the two groups may receive centrally-acting analgesic TRAMCONTIN (Tramadol Hydrochloride Sustained release tablets) as rescue analgesia if VAS score≧3.

Drug: placebo

Interventions

Parecoxib and Celecoxib DRUG

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.

Parecoxib and Celecoxib

placebo DRUG

control patients are supplied with the corresponding placebo with the same instructions.

placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• The subject is a male or female over 18 years of age.
• 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.
• Total duration of the surgical procedure is four hours or less.
• ASA grade 1-3 subjects.
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, standardized rehabilitation scheme, and other study procedures.
• The subject is in satisfactory health as determined by the investigator on the basis of medical history and physical exam.
• The subject must demonstrate sufficient psychomotor dexterity and cognitive capacity to use intravenous (IV) patient-controlled analgesia(PCA).
• The subject who live near to the hospital may be considered prior for the concern of convenient and sufficient follow-up.

You may not qualify if:

• The subject requires a revision to previous knee arthroplasty and/or is having a bilateral knee arthroplasties.
• The subject requires an emergency knee arthroplasty.
• Subject uses opioids more than three days/ week prior to operation unless they discontinue the opioids two months prior to screen.
• Subject has a known hypersensitivity to COX-2 specific inhibitors, sulfonamides, lactose, NSAIDs, opioids or acetaminophen/paracetamol.
• The subject has a history of arthritis:, chronic pain, metastasis, and Paget's disease.
• The subject received any investigational medication within 30 days prior to the first dose of study medication.
• 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.
• 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.
• Subject had any condition, which could preclude use of NSAIDs or COX-2 specific inhibitors.
• The subject has active or suspected esophageal, gastric, pyloric channel, or duodenal ulceration history.
• The subject has received warfarin or other anticoagulants during the 30 days preceding the first dose of study medication.
• Subject is anticipated to require or requires treatment with lithium.
• Subject is American Society of Anesthesiologists(ASA) grade 4-5.
• The subject has a history of a psychiatric disorder requiring new or changing treatment
• The subject has a history of uncontrolled chronic disease or a concurrent clinically significant illness, medical condition.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, 100730, China

Location

Related Publications (9)

• 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.

  PMID: 22398175 BACKGROUND

• Du Q, Ge HJ, Zhu PF. Effects of perioperative analgesia on postoperative inflammatory response. Int J Anesth Resus., 2007, 28(1):48-53.

  BACKGROUND

• 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.

  PMID: 21044725 BACKGROUND

• 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.

  PMID: 21203883 BACKGROUND

• 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.

  PMID: 12083587 BACKGROUND

• 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. doi: 10.1093/bja/aeg038.

  PMID: 12538372 BACKGROUND

• 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. doi: 10.1097/00000542-200603000-00020.

  PMID: 16508400 BACKGROUND

• Zhuang Q, Tao L, Lin J, Jin J, Qian W, Bian Y, Li Y, Dong Y, Peng H, Li Y, Fan Y, Wang W, Feng B, Gao N, Sun T, Lin J, Zhang M, Yan S, Shen B, Pei F, Weng X. Postoperative intravenous parecoxib sodium followed by oral celecoxib post total knee arthroplasty in osteoarthritis patients (PIPFORCE): a multicentre, double-blind, randomised, placebo-controlled trial. BMJ Open. 2020 Jan 9;10(1):e030501. doi: 10.1136/bmjopen-2019-030501.

  PMID: 31924632 DERIVED

• Zhuang Q, Bian Y, Wang W, Jiang J, Feng B, Sun T, Lin J, Zhang M, Yan S, Shen B, Pei F, Weng X. Efficacy and safety of Postoperative Intravenous Parecoxib sodium Followed by ORal CElecoxib (PIPFORCE) post-total knee arthroplasty in patients with osteoarthritis: a study protocol for a multicentre, double-blind, parallel-group trial. BMJ Open. 2016 Sep 8;6(9):e011732. doi: 10.1136/bmjopen-2016-011732.

  PMID: 27609846 DERIVED

MeSH Terms

Conditions

Pain; Inflammation; Agnosia

Interventions

parecoxib; Celecoxib

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Xisheng Weng, M.D.

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Orthopedics

Study Record Dates

• First Submitted: July 17, 2013
• First Posted: July 24, 2014
• Study Start: December 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 19, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)