Parecoxib in Total Knee Arthroplasty

Knee Osteoarthritis Clinical Trial

Official title:

A Randomized Comparison Between Parecoxib and Placebo Added to a Standard Perioperative Analgesic Protocol for Total Knee Arthroplasty

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05924412
• Other study ID #: OAIC1308/22
• Status: Recruiting
• Phase: Phase 4
• Start date: July 6, 2023
• Est. completion date: April 2024

Study information

• Verified date: December 2023
• Source: University of Chile
• Contact: Julián Aliste
• Phone: +56229788209
• Email: julian.aliste[@]uchile.cl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Early mobilization and rehabilitation can be difficult after total knee arthroplasty (TKA) due to a high incidence of moderate to severe postoperative pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are important to multimodal analgesic protocols. Parecoxib is an NSAID that selectively inhibits the enzyme cyclooxygenase-2 (COX-2). Clinical trials have shown that it does not alter platelet function or gastric mucosa. A recent study, after comparing ketorolac and parecoxib used at the same time in infiltration and systemically, found no differences in perioperative analgesia with a tendency to less bleeding in the parecoxib group. This randomized study will compare the effectiveness of adding a COX-2 inhibitor in the pain management of patients undergoing TKA as part of a multimodal analgesia regimen. The morphine consumption was selected as the primary outcome. The study hypothesis is that patients receiving parecoxib would have a lower opioid consumption.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: April 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

ASA I - III BMI 20 - 35 (kg/m2)

Exclusion Criteria:

• Adults who are not capable of giving their own consent
• Pre-existing neuropathy (assessed in the history and physical examination)
• Coagulation disturbance (assessed on history and physical examination, if clinically necessary, by blood test, i.e. platelets = 100,000, international normalized ratio = 1.4 or prothrombin time = 50)
• Renal failure (assessed by history and physical examination, if considered clinically necessary, by blood test, i.e. creatinine = 1.04 mg/dl)
• Hepatic impairment (assessed by history and physical examination, if considered clinically necessary, by blood tests, i.e. transaminases (GGT = 50 u/lt)
• Allergy to local anesthetics, morphine, paracetamol, ketorolac or parecoxib
• Pregnancy
• Chronic pain syndromes that require the use of opioids at home
• Known history of sulfa allergy
• History of ischemic heart disease
• History of chronic gastritis or peptic ulcer

Related Conditions & MeSH terms

• Acute Pain
• Analgesia
• Analgesic Adverse Reaction
• Knee Osteoarthritis
• Pain, Acute
• Pain, Postoperative

Intervention

Drug:
• Intravenous study drug
40mg parecoxib will be administered intravenously after general anesthesia induction and before tourniquet inflation and surgical incisión

Other:
• Intravenous saline solution
Saline solution (same volume as the study drug) will be administered intravenously after general anesthesia induction and before tourniquet inflation and surgical incision

Locations

Country	Name	City	State
Chile	Hospital Clinico Universidad de Chile	Santiago	Metropolitan

Sponsors (1)

Lead Sponsor	Collaborator
University of Chile

Country where clinical trial is conducted

Chile, 

References & Publications (13)

Affas F, Eksborg S, Wretenberg P, Olofsson C, Stephanson N, Stiller CO. Plasma concentration of ketorolac after local infiltration analgesia in hip arthroplasty. Acta Anaesthesiol Scand. 2014 Oct;58(9):1140-5. doi: 10.1111/aas.12371. Epub 2014 Jul 31. — View Citation

Andersen LO, Kehlet H. Analgesic efficacy of local infiltration analgesia in hip and knee arthroplasty: a systematic review. Br J Anaesth. 2014 Sep;113(3):360-74. doi: 10.1093/bja/aeu155. Epub 2014 Jun 17. — View Citation

Aso K, Izumi M, Sugimura N, Okanoue Y, Kamimoto Y, Yokoyama M, Ikeuchi M. Additional benefit of local infiltration of analgesia to femoral nerve block in total knee arthroplasty: double-blind randomized control study. Knee Surg Sports Traumatol Arthrosc. — View Citation

Bai JW, An D, Perlas A, Chan V. Adjuncts to local anesthetic wound infiltration for postoperative analgesia: a systematic review. Reg Anesth Pain Med. 2020 Aug;45(8):645-655. doi: 10.1136/rapm-2020-101593. Epub 2020 May 30. — View Citation

Chan E, Howle R, Onwochei D, Desai N. Infiltration between the popliteal artery and the capsule of the knee (IPACK) block in knee surgery: a narrative review. Reg Anesth Pain Med. 2021 Sep;46(9):784-805. doi: 10.1136/rapm-2021-102681. Epub 2021 May 14. — View Citation

Chou R, Gordon DB, de Leon-Casasola OA, Rosenberg JM, Bickler S, Brennan T, Carter T, Cassidy CL, Chittenden EH, Degenhardt E, Griffith S, Manworren R, McCarberg B, Montgomery R, Murphy J, Perkal MF, Suresh S, Sluka K, Strassels S, Thirlby R, Viscusi E, W — View Citation

Harris SI, Kuss M, Hubbard RC, Goldstein JL. Upper gastrointestinal safety evaluation of parecoxib sodium, a new parenteral cyclooxygenase-2-specific inhibitor, compared with ketorolac, naproxen, and placebo. Clin Ther. 2001 Sep;23(9):1422-8. doi: 10.1016 — View Citation

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. — View Citation

Laoruengthana A, Rattanaprichavej P, Reosanguanwong K, Chinwatanawongwan B, Chompoonutprapa P, Pongpirul K. A randomized controlled trial comparing the efficacies of ketorolac and parecoxib for early pain management after total knee arthroplasty. Knee. 20 — View Citation

Sankineani SR, Reddy ARC, Eachempati KK, Jangale A, Gurava Reddy AV. Comparison of adductor canal block and IPACK block (interspace between the popliteal artery and the capsule of the posterior knee) with adductor canal block alone after total knee arthro — View Citation

Seangleulur A, Vanasbodeekul P, Prapaitrakool S, Worathongchai S, Anothaisintawee T, McEvoy M, Vendittoli PA, Attia J, Thakkinstian A. The efficacy of local infiltration analgesia in the early postoperative period after total knee arthroplasty: A systemat — View Citation

Stoltz RR, Harris SI, Kuss ME, LeComte D, Talwalker S, Dhadda S, Hubbard RC. Upper GI mucosal effects of parecoxib sodium in healthy elderly subjects. Am J Gastroenterol. 2002 Jan;97(1):65-71. doi: 10.1111/j.1572-0241.2002.05265.x. — View Citation

Summers S, Mohile N, McNamara C, Osman B, Gebhard R, Hernandez VH. Analgesia in Total Knee Arthroplasty: Current Pain Control Modalities and Outcomes. J Bone Joint Surg Am. 2020 Apr 15;102(8):719-727. doi: 10.2106/JBJS.19.01035. No abstract available. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Morphine consumption	Morphine consumed postoperatively during the first 24 hrs utilizing a patient-controlled analgesia device programmed 1mg/ml morphine solution, no infusion, 1ml dose, 8 minutes lockout.	24 hours
Secondary	Basal quadriceps strength in the operative side	Leg extension strength measured with a handheld dynamometer	1 hour before surgery
Secondary	Basal level of pain during leg extension in the operative side	Pain level measured with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain)	1 hour before surgery
Secondary	Basal plasmatic creatinine	Plasmatic creatinine level measured in mg/dL from a blood sample	1 hour before surgery
Secondary	Nerve block performance time	Time elapsed between skin disinfection and the end of local anesthetic injection in femoral triangle and posterior capsule blocks.	5 minutes after anesthesia induction (before surgical incision)
Secondary	Incidence of Block complications	Report of vascular puncture, hematoma, local anesthetic systemic toxicity symptoms	5 minutes after anesthesia induction and before surgical incision
Secondary	Time to first morphine dose request	Time in minutes between arrival to post anesthesia care unit arrival and first request of morphine with the patient controlled analgesia device	24 hours
Secondary	Morphine consumption during first 48 hours	Morphine consumed postoperatively during the first 48 hrs utilizing a patient-controlled analgesia device programmed 0.01mg/Kg/ml morphine solution, no infusion, 1ml dose, 8 minutes lockout.	48 hours
Secondary	Incidence of opioid related side effects	Report of nausea, vomitus, pruritus, urinary retention, respiratory depression	48 hours
Secondary	Incidence of NSAIDs related clinical side effects	Report of allergic reactions, pyrosis, evident gastrointestinal bleeding, hematoma	48 hours
Secondary	Postoperative static pain level at 3 hours	Pain level measured at rest with an 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain)	3 hours
Secondary	Postoperative dynamic pain level at 3 hours	Pain level measured during leg extension with an 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain)	3 hours
Secondary	Postoperative static pain level at 6 hours	Pain level measured at rest with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain)	6 hours
Secondary	Postoperative dynamic pain level at 6 hours	Pain level measured during leg extension with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain)	6 hours
Secondary	Postoperative static pain level at 12 hours	Pain level measured at rest with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain)	12 hours
Secondary	Postoperative dynamic pain level at 12 hours	Pain level measured during leg extension with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain)	12 hours
Secondary	Postoperative static pain level at 24 hours	Pain level measured at rest with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain)	24 hours
Secondary	Postoperative dynamic pain level at 24 hours	Pain level measured during leg extension with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain)	24 hours
Secondary	Postoperative static pain level at 48 hours	Pain level measured at rest with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain)	48 hours
Secondary	Postoperative dynamic pain level at 48 hours	Pain level measured during leg extension with a 11-points numeric rating scale (from 0 to 10 where 0 means absence of pain and 10 the worst imaginable pain)	48 hours
Secondary	Medial malleolus sensory block level	0 to 2 points for Sensory block to cold and touch in the medial malleolus. 0 point= can feel cold and touch; 1= can feel touch but not cold; 2= cannot feel cold or touch	3 hours
Secondary	Lateral malleolus sensory block level	0 to 2 points for Sensory block to cold and touch in the medial malleolus. 0 point= can feel cold and touch; 1= can feel touch but not cold; 2= cannot feel cold or touch	3hours
Secondary	Medial malleolus sensory block level	0 to 2 points for Sensory block to cold and touch in the medial malleolus. 0 point= can feel cold and touch; 1= can feel touch but not cold; 2= cannot feel cold or touch	24 hours
Secondary	Lateral malleolus sensory block level	0 to 2 points for Sensory block to cold and touch in the medial malleolus. 0 point= can feel cold and touch; 1= can feel touch but not cold; 2= cannot feel cold or touch	24 hours
Secondary	Postoperative quadriceps strength	Leg extension strength measured with a handheld dynamometer	3 hours
Secondary	Postoperative quadriceps strength	Leg extension strength measured with a handheld dynamometer	24 hours
Secondary	Incidence of restriction to perform physiotherapy	Inability to perform physiotherapy secondary to pain or motor blockade	6 hours
Secondary	Incidence of restriction to perform physiotherapy	Inability to perform physiotherapy secondary to pain or motor blockade	24 hours
Secondary	Incidence of restriction to perform physiotherapy	Inability to perform physiotherapy secondary to pain or motor blockade	48 hours
Secondary	Postoperative plasmatic creatinine level	Plasmatic creatinine level measured in mg/dL from a blood sample	48 hours