Analgesic Efficacy of Different Liposomal Bupivacaine Doses in the Adductor Canal Block for Total Knee Arthroplasty

NCT06740214 | Recruiting Phase 3

• 1 other identifier: UW24-691
• Study Type: interventional
• Target: 177
• Locations: 1 country
• Sites: 1

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 robotic assisted total knee arthroplasty. The investigators will also assess secondary outcomes including knee functional scores, chronic pain and quality of recovery.

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

Outcome Measures

Primary Outcomes (1)

• Weighted area under curve (AUC) pain score

  Pain severity would be rated at rest after surgery using numerical rating scale (NRS) with 0 to 10 where 0=no pain and 10=the worst possible pain

  The first 48 hours after surgery when the patient is at rest

Secondary Outcomes (19)

• NRS pain scores

  from after surgery to postoperative day 7

• Oxynorm consumption

  Postoperative day 1-7

• Overall Benefit of Analgesic Score (OBAS)

  Postoperative day (POD) 1-7

• Plasma level of bupivacaine and ropivacaine

  Blood will be collected during induction, at 12 hours, 24 hours, 48 hours, and 72 hours after ACB.

• Quality of Recovery Questionnaire (QoR-9)

  Postoperative day 1

Study Arms (3)

ACB using 20ml 0.5% standard bupivacaine (SB-ACB)

ACTIVE COMPARATOR

adductor canal block with 20ml 0.5% standard bupivacaine only

Drug: 0.5% standard bupivacaine only

ACB using 10ml 1.33% liposomal bupivacaine with 10 ml 0.5% standard bupivacaine (LB10-ACB)

EXPERIMENTAL

adductor canal block with 10ml 1.33% liposomal bupivacaine (133mg) plus 10ml 0.5% standard bupivacaine

Drug: 1.33% liposomal bupivacaine with 0.5% standard bupivacaine

ACB using 20ml 1.33% liposomal bupivacaine only (LB20-ACB)

EXPERIMENTAL

adductor canal block with 20ml 1.33% liposomal bupivacaine (266mg)

Drug: 1.33% liposomal bupivacaine only

Interventions

1.33% liposomal bupivacaine with 0.5% standard bupivacaine DRUG

10ml 1.33% liposomal bupivacaine (133mg) plus 10ml 0.5% standard bupivacaine

ACB using 10ml 1.33% liposomal bupivacaine with 10 ml 0.5% standard bupivacaine (LB10-ACB)

0.5% standard bupivacaine only DRUG

20ml 0.5% standard bupivacaine only

ACB using 20ml 0.5% standard bupivacaine (SB-ACB)

1.33% liposomal bupivacaine only DRUG

20ml 1.33% liposomal bupivacaine (266mg)

ACB using 20ml 1.33% liposomal bupivacaine only (LB20-ACB)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

The University of Hong Kong

Hong Kong, Hong Kong, Hong Kong

RECRUITING

Related Publications (17)

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  PMID: 18806027 RESULT

• 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.

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  RESULT

• 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.

  PMID: 38297390 RESULT

• 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.

  PMID: 35351553 RESULT

• 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.

  PMID: 34556382 RESULT

• 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.

  PMID: 34292820 RESULT

• 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.

  PMID: 32776794 RESULT

• 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.

  PMID: 30544393 RESULT

• 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.

  PMID: 30971284 RESULT

• 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.

  PMID: 33372949 RESULT

• 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.

  PMID: 27627711 RESULT

• Rawal N. Current issues in postoperative pain management. Eur J Anaesthesiol. 2016 Mar;33(3):160-71. doi: 10.1097/EJA.0000000000000366.

  PMID: 26509324 RESULT

• 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.

  PMID: 35852550 RESULT

MeSH Terms

Conditions

Pain, Postoperative

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Central Study Contacts

Stanley S.C. WONG, MD (HKU)

CONTACT

(852) 2255 3303; wongstan@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: November 29, 2024
• First Posted: December 18, 2024
• Study Start: September 4, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: November 24, 2025

Record last verified: 2025-11

Locations

HK (1)