PainPhase 4NCT02198924
Efficacy and Safety of Postoperative Intravenous Parecoxib Sodium Followed by Oral Celecoxib in Osteoarthritis Patients
A Phase 4 study testing Parecoxib and Celecoxib in people with Pain and Inflammation, run by Peking Union Medical College Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Pain, Inflammation
- What is being tested?
- Parecoxib and Celecoxib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 246 participants
- Where
- 1 siteChina
- Study dates
- Dec 2014to Dec 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
- -
Who cannot join
- 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.
Show all 24Show fewer
- 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.
- 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.
- Subject has a history of asthma or bronchospasm, which requires treatment with glucocorticoids.
- Subject had a history of alcohol, analgesic or narcotic abuse.
- Subject has been previously randomized into the study
- Subjects who are investigational site staff members or relatives of those site staff
- Participation in other studies within 3 months before the current study begins and/or during study participation
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation.
- Pregnant females, breastfeeding females, or males and females of childbearing potential not using effective contraception.
- -
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Pain, Inflammation
- Being tested
- Parecoxib and Celecoxib, placebo
- Keywords
- sequential administration, pain control, inflammation control, function recovery
- Medical subject headings
- Pain, Inflammation, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Parecoxib and CelecoxibDrug
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.
placeboDrug
control patients are supplied with the corresponding placebo with the same instructions.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Post-operative 2 WEEKS
Secondary outcomes (7)
Knee Society Score
For more than 20 years, The Knee Society's Knee Scoring System (KSS) has served as a simple, objective way to measure a patient's functional ability before and after total knee arthroplasty (TKA). KSS questionnaire generates three domain scores: KSS function score (walking, stairs and use of knee supports), range of motion and KSS score (pain, range of motion and stability) scores.
Measured: post-operation 6 weeks
Western Ontario and McMaster Universities Arthritis(WOMAC) Index
The WOMAC is a widely used, proprietary set of standardized questionnaires to evaluate the condition of patients with knee osteoarthritis , including pain, stiffness, and physical functioning of the joints. A WOMAC test takes about 12 minutes, and is among the most widely used assessments in arthritis research.
Measured: prior to operation and at 2w,4w and 6w post operation
Knee Society Score
For more than 20 years, The Knee Society's Knee Scoring System (KSS) has served as a simple, objective way to measure a patient's functional ability before and after total knee arthroplasty (TKA). KSS questionnaire generates three domain scores: KSS function score (walking, stairs and use of knee supports), range of motion and KSS score (pain, range of motion and stability) scores.
Measured: prior to operation and at 2w and 4w post operation
Total Morphine use
The cumulative Morphine consumption over the first 24 hours postsurgical period.
Measured: over the first 24 hours postsurgical period
Total narcotic use
The cumulative Morphine consumption and opioid drug over the first 24 hours postsurgical period.
Measured: 72h, 4w, 6w post operation
Visual Analogue Scale
A Visual Analogue Scale (VAS) is a measurement instrument that tries to measure a characteristic or attitude that is believed to range across a continuum of values and cannot easily be directly measured.
Operationally a VAS is usually a horizontal line, 100 mm in length, anchored by word descriptors at each end. The patient marks on the line the point that they feel represents their perception of their current state. The VAS score is determined by measuring in millimetres from the left hand end of the line to the point that the patient marks.
Measured: prior to operation and at 24h, 48h, 72h, 2w, 4w and 6w post operation
EuroQol (EQ-5D) Score
EQ-5D is a standard instrument for use as a measure of health outcome. EQ-5D is primarily designed for self-completion by respondents and is ideally suited for use in postal surveys, in clinics and face-to-face interviews. It is cognitively simple, taking only a few minutes to complete. Instructions to respondents are included in the questionnaire.
Measured: prior to operation and 72h, 2w, 4w and 6w post operation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2014 (estimated)
- Study startDec 2014
- Primary completionNov 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 246 participants (actual)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xisheng Weng, Peking Union Medical College Hospital
- Investigators
- Xisheng Weng, M.D., Principal investigator, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02198924
- Sponsor's protocol ID
- WI1180091
- Status last verified
- Apr 2019
- First submitted
- 17 Jul 2013
- Last updated
- 19 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
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.
PubMed 22398175Du 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.
PubMed 21044725Honsawek 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.
PubMed 21203883Rasmussen 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.
PubMed 12083587Hubbard 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.
PubMed 12538372Nussmeier 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.
PubMed 16508400Zhuang 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.
PubMed 31924632Zhuang 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.
PubMed 27609846
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02198924
- Acronym / sponsor ID
- WI1180091
- Conditions
- Pain, Inflammation
- Keywords
- sequential administration, pain control, inflammation control, function recovery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 246 participants (actual)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- Dec 2014 (actual)
- Primary completion
- Nov 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 24 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Parecoxib and Celecoxib | Experimental | Drug: Parecoxib and CelecoxibPatients 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. |
| placebo | Placebo comparator | Drug: placeboPatients 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. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Parecoxib and CelecoxibPatients 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. | Drug | Parecoxib and Celecoxib |
| placebocontrol patients are supplied with the corresponding placebo with the same instructions. | Drug | placebo |
Primary outcome
Total narcotic use
Time frame: Post-operative 2 WEEKS
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.
7 secondary outcomes
Knee Society Score
Time frame: post-operation 6 weeks
Western Ontario and McMaster Universities Arthritis(WOMAC) Index
Time frame: prior to operation and at 2w,4w and 6w post operation
Knee Society Score
Time frame: prior to operation and at 2w and 4w post operation
Total Morphine use
Time frame: over the first 24 hours postsurgical period
Total narcotic use
Time frame: 72h, 4w, 6w post operation
Visual Analogue Scale
Time frame: prior to operation and at 24h, 48h, 72h, 2w, 4w and 6w post operation
EuroQol (EQ-5D) Score
Time frame: prior to operation and 72h, 2w, 4w and 6w post operation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2019.
- Background: PubMed 22398175Carr 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.
- BackgroundDu Q, Ge HJ, Zhu PF. Effects of perioperative analgesia on postoperative inflammatory response. Int J Anesth Resus., 2007, 28(1):48-53.
- Background: PubMed 21044725Holm 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.
- Background: PubMed 21203883Honsawek 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.
- Background: PubMed 12083587Rasmussen 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.
- Background: PubMed 12538372Hubbard 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.
- Background: PubMed 16508400Nussmeier 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.
- Derived from this study: PubMed 31924632Zhuang 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.
- Derived from this study: PubMed 27609846Zhuang 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xisheng Weng, M.D. principal investigator
Peking Union Medical College Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Parecoxib and Celecoxib in people with Pain and Inflammation, run by Peking Union Medical College Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total narcotic use (time frame: Post-operative 2 WEEKS). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02198924, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2019.