Clinical trial NCT06740214: Analgesic Efficacy of Different Liposomal Bupivacaine Doses in the Adductor Canal Block for Total Knee Arthroplasty
Official title: Analgesic Efficacy of Different Liposomal Bupivacaine Doses in the Adductor Canal Block for Total Knee Arthroplasty: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Pain, Postoperative
Analgesic Effect
Total Knee Arthroplasty
Liposomal Bupivacaine
Dose Response Relationship, Drug
Keywords: adductor canal block
local infiltration analgesia
liposomal bupivacaine
opioid consumption
total knee arthroplasty
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2024-12-18
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Total knee arthroplasty is a commonly performed orthopaedic surgery for the treatment of end-stage osteoarthritis when conservative management becomes ineffective. TKA is associated with significant acute postoperative pain and many patients experience severe postoperative pain despite the use of multimodal analgesia. Poor acute postoperative pain control impacts rehabilitation, prolongs recovery and increases opioid consumption and chronic post-surgical pain.

Liposomal bupivacaine (Exparel, Pacira Pharmaceuticals Inc, Parsippany, New Jersey, USA) is a multivesicular formulation of bupivacaine that prolongs drug release and can extend the duration of analgesia. The adductor canal block (ACB) has been shown to reduce pain intensity and opioid consumption after total knee arthroplasty. The use of liposomal bupivacaine in the adductor canal block has recently been FDA-approved. However, the results of its efficacy from existing clinical trials have been mixed. In addition, the doses in the clinical trials have been different, and the optimal dose for perineural application of liposomal bupivacaine is unclear, including for the adductor canal block.

In this project, the investigators propose to conduct a randomized controlled trial to investigate the effect of different doses of liposomal bupivacaine in the adductor canal block on acute postoperative pain intensity and opioid consumption after total knee arthroplasty. The investigators will also assess secondary outcomes including knee functional scores, chronic pain and quality of recovery.


Eligibility criteria: Inclusion Criteria:

* ASA I-III
* Age 18-80 years old
* Scheduled for elective primary unilateral total knee arthroplasty (TKA)
* Able to speak and understand Cantonese or Mandarin or English
* Able to provide informed oral and written consent

Exclusion Criteria:

* Revision TKA
* Single-stage bilateral TKA
* Complex primary TKA requiring use of stem/augment/constrained liner
* Surgeries with significant intraoperative complications which may alter rehabilitation protocol eg collateral ligament injury, fracture requiring fixation
* Known allergy to opioids, local anaesthetic drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDS) including COX-2 inhibitors
* History of chronic pain other than chronic knee pain
* History of immunosuppression
* Chronic use of glucocorticoids
* Chronic opioid use (morphine, fentanyl, hydromorphone, ketobemidone, methadone, nicomorphine, oxycodone, or meperidine)
* History of congestive heart failure (NYHA 2)
* Alcohol or drug abuse
* Impaired renal function (defined as effective glomerular filtration rate \< 30ml/min/1.73m2
* Impaired liver function (defined as plasma bilirubin over 34mol/L; international normalized ratio \[INR\] \>= 1.7, alanine aminotransferase \[ALT\] over 100U/L, aspartate aminotransferase \[AST\] over 100U/L)
* Coagulopathy (platelet count \<100,000/ml and/or INR \>= 1.5) or the use of anticoagulants (not including aspirin) that precludes the use of adductor canal blocks
* Pre-existing neurological or muscular disorders
* Psychiatric illness
* Impaired mental state
* Pregnancy
* Local infection
* On immunosuppressants
* High body mass index (BMI) (\>=40)
* Patient refusal for regional nerve blocks or to conduct clinical trial

Primary outcomes:
measure: Weighted area under curve (AUC) pain score
timeFrame: The first 48 hours after surgery when the patient is at rest
Secondary outcomes:
measure: NRS pain scores
timeFrame: from after surgery to postoperative day 7
measure: Oxynorm consumption
timeFrame: Postoperative day 1-7
measure: Overall Benefit of Analgesic Score (OBAS)
timeFrame: Postoperative day (POD) 1-7
measure: Plasma level of bupivacaine and ropivacaine
timeFrame: Blood will be collected during induction, at 2 hours, 8 hours, 24 hours, and 48 hours after ACB.
measure: Quality of Recovery Questionnaire (QoR-9)
timeFrame: Postoperative day 1
measure: Rehabilitation parameters (range of maximal active knee flexion)
timeFrame: While the patient is in hospital from postoperative day 0, day 1, and day 2.
measure: Rehabilitation parameters (quadricep power)
timeFrame: While the patient is in hospital from postoperative day 0, day 1, and day 2.
measure: Rehabilitation parameters (ability to perform straight leg raising)
timeFrame: While the patient is in hospital from postoperative day 0, day 1, and day 2.
measure: Rehabilitation parameters (walking distance)
timeFrame: While the patient is in hospital from postoperative day 0, day 1, and day 2.
measure: Rehabilitation parameters (Duration of hospital stay)
timeFrame: estimated on average of postoperative day 7 at the date of discharge from hospital
measure: Rehabilitation parameters (discharge location)
timeFrame: estimated on average of postoperative day 7 at the date of discharge from hospital
measure: Opioid-related side effects
timeFrame: While the patient is in hospital from postoperative day 0, 1, and 2.
measure: Potential side effects related to adductor canal block (ACB)
timeFrame: While the patient is in hospital from postoperative day 0, 1, and 2.
measure: Analgesic block duration
timeFrame: While the patient is in hospital at postoperative day 1
measure: Sensory and motor assessment
timeFrame: While the patient is in hospital from post-block 2 hours, 6 hours, 12 hours, and 24 hours.
measure: quality of life (SF12v2)
timeFrame: at 6 weeks and at 3 and 6 months after surgery
measure: Identification Pain Questionnaire for Neuropathic Pain (ID-NeP)
timeFrame: at 6 weeks, 3 months and 6 months postoperatively
measure: Knee Society Knee Function Score
timeFrame: at 6 weeks, 3 months and 6 months postoperatively
measure: Chronic post-surgical pain
timeFrame: at 6 weeks, 3 months and 6 months postoperatively
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong
Study officials:
References:
citation: Culliton SE, Bryant DM, MacDonald SJ, Hibbert KM, Chesworth BM. Validity and Internal Consistency of the New Knee Society Knee Scoring System. Clin Orthop Relat Res. 2018 Jan;476(1):77-84. doi: 10.1007/s11999.0000000000000014.
citation: Portenoy R. Development and testing of a neuropathic pain screening questionnaire: ID Pain. Curr Med Res Opin. 2006 Aug;22(8):1555-65. doi: 10.1185/030079906X115702.
citation: Chan MT, Lo CC, Lok CK, Chan TW, Choi KC, Gin T. Psychometric testing of the Chinese quality of recovery score. Anesth Analg. 2008 Oct;107(4):1189-95. doi: 10.1213/ane.0b013e318184b94e.
citation: Lam ET, Lam CL, Fong DY, Huang WW. Is the SF-12 version 2 Health Survey a valid and equivalent substitute for the SF-36 version 2 Health Survey for the Chinese? J Eval Clin Pract. 2013 Feb;19(1):200-8. doi: 10.1111/j.1365-2753.2011.01800.x. Epub 2011 Nov 29.
citation: Lehmann N, Joshi GP, Dirkmann D, Weiss M, Gulur P, Peters J, Eikermann M. Development and longitudinal validation of the overall benefit of analgesia score: a simple multi-dimensional quality assessment instrument. Br J Anaesth. 2010 Oct;105(4):511-8. doi: 10.1093/bja/aeq186. Epub 2010 Aug 6.
citation: Cohen, J., Statistical power analysis for the behavioral sciences. 2013: routledge.
citation: Quaye A, McAllister B, Garcia JR, Nohr O, Laduzenski SJ, Mack L, Kerr CR, Kerr DA, Razafindralay CN, Richard JM, Craig WY, Rodrigue S. A prospective, randomized trial of liposomal bupivacaine compared to conventional bupivacaine on pain control and postoperative opioid use in adults receiving adductor canal blocks for total knee arthroplasty. Arthroplasty. 2024 Feb 1;6(1):6. doi: 10.1186/s42836-023-00226-y.
citation: Malige A, Pellegrino AN, Kunkle K, Konopitski AK, Brogle PJ, Nwachuku CO. Liposomal Bupivacaine in Adductor Canal Blocks Before Total Knee Arthroplasty Leads to Improved Postoperative Outcomes: A Randomized Controlled Trial. J Arthroplasty. 2022 Aug;37(8):1549-1556. doi: 10.1016/j.arth.2022.03.073. Epub 2022 Mar 26.
citation: Hungerford M, Neubauer P, Ciotola J, Littleton K, Boner A, Chang L. Liposomal Bupivacaine vs Ropivacaine for Adductor Canal Blocks in Total Knee Arthroplasty: A Prospective Randomized Trial. J Arthroplasty. 2021 Dec;36(12):3915-3921. doi: 10.1016/j.arth.2021.08.017. Epub 2021 Aug 21.
citation: Hubler CP, Bevil KM, Greiner JJ, Hetzel SJ, Borden SB, Cios HA. Liposomal Bupivacaine Versus Standard Bupivacaine in the Adductor Canal for Total Knee Arthroplasty: A Randomized, Controlled Trial. Orthopedics. 2021 Jul-Aug;44(4):249-255. doi: 10.3928/01477447-20210621-01. Epub 2021 Jul 1.
citation: Lv J, Huang C, Wang Z, Ou S. Adductor canal block combined with local infiltration analgesia versus isolated adductor canal block in reducing pain and opioid consumption after total knee arthroplasty: a systematic review and meta-analysis. J Int Med Res. 2020 Aug;48(8):300060520926075. doi: 10.1177/0300060520926075.
citation: Li Y, Li A, Zhang Y. The efficacy of combined adductor canal block with local infiltration analgesia for pain control after total knee arthroplasty: A meta-analysis. Medicine (Baltimore). 2018 Dec;97(49):e13326. doi: 10.1097/MD.0000000000013326.
citation: Zuo W, Guo W, Ma J, Cui W. Dose adductor canal block combined with local infiltration analgesia has a synergistic effect than adductor canal block alone in total knee arthroplasty: a meta-analysis and systematic review. J Orthop Surg Res. 2019 Apr 11;14(1):101. doi: 10.1186/s13018-019-1138-5.
citation: Ilfeld BM, Eisenach JC, Gabriel RA. Clinical Effectiveness of Liposomal Bupivacaine Administered by Infiltration or Peripheral Nerve Block to Treat Postoperative Pain. Anesthesiology. 2021 Feb 1;134(2):283-344. doi: 10.1097/ALN.0000000000003630.
citation: Jiang X, Wang QQ, Wu CA, Tian W. Analgesic Efficacy of Adductor Canal Block in Total Knee Arthroplasty: A Meta-analysis and Systematic Review. Orthop Surg. 2016 Aug;8(3):294-300. doi: 10.1111/os.12268.
citation: Rawal N. Current issues in postoperative pain management. Eur J Anaesthesiol. 2016 Mar;33(3):160-71. doi: 10.1097/EJA.0000000000000366.
citation: Lavand'homme PM, Kehlet H, Rawal N, Joshi GP; PROSPECT Working Group of the European Society of Regional Anaesthesia and Pain Therapy (ESRA). Pain management after total knee arthroplasty: PROcedure SPEcific Postoperative Pain ManagemenT recommendations. Eur J Anaesthesiol. 2022 Sep 1;39(9):743-757. doi: 10.1097/EJA.0000000000001691. Epub 2022 Jul 20.