Clinical trial NCT05924412: Parecoxib in Total Knee Arthroplasty
Official title: A Randomized Comparison Between Parecoxib and Placebo Added to a Standard Perioperative Analgesic Protocol for Total Knee Arthroplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pain, Postoperative
Pain, Acute
Analgesia
Analgesic Nephropathy
Analgesic Adverse Reaction
Knee Osteoarthritis
Lead sponsor: University of Chile
Sponsor class: OTHER
First posted: 2023-06-29
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Morphine consumption
timeFrame: 24 hours
Secondary outcomes:
measure: Basal quadriceps strength in the operative side
timeFrame: 1 hour before surgery
measure: Basal level of pain during leg extension in the operative side
timeFrame: 1 hour before surgery
measure: Basal plasmatic creatinine
timeFrame: 1 hour before surgery
measure: Nerve block performance time
timeFrame: 5 minutes after anesthesia induction (before surgical incision)
measure: Incidence of Block complications
timeFrame: 5 minutes after anesthesia induction and before surgical incision
measure: Time to first morphine dose request
timeFrame: 24 hours
measure: Morphine consumption during first 48 hours
timeFrame: 48 hours
measure: Incidence of opioid related side effects
timeFrame: 48 hours
measure: Incidence of NSAIDs related clinical side effects
timeFrame: 48 hours
measure: Postoperative static pain level at 3 hours
timeFrame: 3 hours
measure: Postoperative dynamic pain level at 3 hours
timeFrame: 3 hours
measure: Postoperative static pain level at 6 hours
timeFrame: 6 hours
measure: Postoperative dynamic pain level at 6 hours
timeFrame: 6 hours
measure: Postoperative static pain level at 12 hours
timeFrame: 12 hours
measure: Postoperative dynamic pain level at 12 hours
timeFrame: 12 hours
measure: Postoperative static pain level at 24 hours
timeFrame: 24 hours
measure: Postoperative dynamic pain level at 24 hours
timeFrame: 24 hours
measure: Postoperative static pain level at 48 hours
timeFrame: 48 hours
measure: Postoperative dynamic pain level at 48 hours
timeFrame: 48 hours
measure: Medial malleolus sensory block level
timeFrame: 3 hours
measure: Lateral malleolus sensory block level
timeFrame: 3hours
measure: Medial malleolus sensory block level
timeFrame: 24 hours
measure: Lateral malleolus sensory block level
timeFrame: 24 hours
measure: Postoperative quadriceps strength
timeFrame: 3 hours
measure: Postoperative quadriceps strength
timeFrame: 24 hours
measure: Incidence of restriction to perform physiotherapy
timeFrame: 6 hours
measure: Incidence of restriction to perform physiotherapy
timeFrame: 24 hours
measure: Incidence of restriction to perform physiotherapy
timeFrame: 48 hours
measure: Postoperative plasmatic creatinine level
timeFrame: 48 hours
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Hospital Clinico Universidad de Chile
state: Metropolitan
Study officials:
References:
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. 2019 Jul;27(7):2368-2374. doi: 10.1007/s00167-018-5322-7. Epub 2018 Dec 8.
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, Walco GA, Warner L, Weisman SJ, Wu CL. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016 Feb;17(2):131-57. doi: 10.1016/j.jpain.2015.12.008.
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.
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.
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.
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/s0149-2918(01)80117-x.
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.
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 systematic review and meta-analysis. Eur J Anaesthesiol. 2016 Nov;33(11):816-831. doi: 10.1097/EJA.0000000000000516.
citation: 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.
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. 2020 Dec;27(6):1708-1714. doi: 10.1016/j.knee.2020.10.005. Epub 2020 Nov 13.
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.
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.
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 arthroplasty: a prospective control trial on pain and knee function in immediate postoperative period. Eur J Orthop Surg Traumatol. 2018 Oct;28(7):1391-1395. doi: 10.1007/s00590-018-2218-7. Epub 2018 May 2.