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

Phase 3

Not yet recruiting

• Conditions: Pain, Postoperative; Analgesic Effect; Total Knee Arthroplasty; Liposomal Bupivacaine; Dose Response Relationship, Drug
• Interventions: Drug: 0.5% standard bupivacaine only; Drug: 1.33% liposomal bupivacaine with 0.5% standard bupivacaine; Drug: 1.33% liposomal bupivacaine only

• Registration Number: NCT06740214
• Lead Sponsor: The University of Hong Kong

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-29
• Study First Submitted QC: 2024-12-13
• Status Verified: 2025-03
• Study First Posted: 2025-03-25
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-26
• Study Start: 2025-07-01
• Primary Completion: 2027-06-30
• Study Completion: 2028-06-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 177

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ACB using 20ml 0.5% standard bupivacaine (SB-ACB)	0.5% standard bupivacaine only	adductor canal block with 20ml 0.5% standard bupivacaine only
ACB using 10ml 1.33% liposomal bupivacaine with 10 ml 0.5% standard bupivacaine (LB10-ACB)	1.33% liposomal bupivacaine with 0.5% standard bupivacaine	adductor canal block with 10ml 1.33% liposomal bupivacaine (133mg) plus 10ml 0.5% standard bupivacaine
ACB using 20ml 1.33% liposomal bupivacaine only (LB20-ACB)	1.33% liposomal bupivacaine only	adductor canal block with 20ml 1.33% liposomal bupivacaine (266mg)

Primary Outcome Measures

Name	Time	Method
Weighted area under curve (AUC) pain score	The first 48 hours after surgery when the patient is at rest	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

Secondary Outcome Measures

Name	Time	Method
NRS pain scores	from after surgery to postoperative day 7	NRS pain scores at rest and with movement (active knee flexion) from after surgery to postoperative day (POD) 7, ranging 0-10, with higher scores indicating more severe pain.
Oxynorm consumption	Postoperative day 1-7	Oxynorm consumption from postoperative day (POD) 1-7
Overall Benefit of Analgesic Score (OBAS)	Postoperative day (POD) 1-7	Overall Benefit of Analgesic Score (OBAS) from postoperative day (POD) 1-7 (range, 0 \[best\] to 28 \[worst\])
Plasma level of bupivacaine and ropivacaine	Blood will be collected during induction, at 2 hours, 8 hours, 24 hours, and 48 hours after ACB.	Plasma level of bupivacaine and ropivacaine before and after surgery
Quality of Recovery Questionnaire (QoR-9)	Postoperative day 1	Quality of Recovery Questionnaire (QoR-9) on postoperative day 1, ranging from 0 to 18, with higher scores indicating good recovery after anaesthesia.
Rehabilitation parameters (range of maximal active knee flexion)	While the patient is in hospital from postoperative day 0, day 1, and day 2.	Range of maximal active knee flexion will be assessed by the physiotherapists while the patient is in hospital.
Rehabilitation parameters (quadricep power)	While the patient is in hospital from postoperative day 0, day 1, and day 2.	Quadricep power will be assessed by the physiotherapists while the patient is in hospital.; Ratings: 0 - no muscle contraction; 1. - Move w/o gravity; 2. - Raise then drop down immediately; 3. - Raise against gravity w/o resistance; 4. - Raise against gravity w/some resistance; 5. - Raise against gravity w/ full resistance
Rehabilitation parameters (ability to perform straight leg raising)	While the patient is in hospital from postoperative day 0, day 1, and day 2.	Ability to perform straight leg raising will be assessed by the physiotherapists while the patient is in hospital. Ratings (Yes/ No).
Rehabilitation parameters (walking distance)	While the patient is in hospital from postoperative day 0, day 1, and day 2.	Walking distance (in metres) will be assessed by the physiotherapists while the patient is in hospital.
Rehabilitation parameters (Duration of hospital stay)	estimated on average of postoperative day 7 at the date of discharge from hospital	No. of hospitalization days from admission to discharge
Rehabilitation parameters (discharge location)	estimated on average of postoperative day 7 at the date of discharge from hospital	Home or rehabilitation center
Opioid-related side effects	While the patient is in hospital from postoperative day 0, 1, and 2.	Presence or absence of pruritus, dizziness, nausea, and vomiting will be recorded.
Potential side effects related to adductor canal block (ACB)	While the patient is in hospital from postoperative day 0, 1, and 2.	Presence or absence of local anaesthetic toxicity, neurological injury, and intravascular injection will be recorded.
Analgesic block duration	While the patient is in hospital at postoperative day 1	Measured in time to return of pain (When did your pain relief from the block completely wear off?), time to sensory resolution (When did your numbness completely resolve and return to normal?), and time to motor resolution (When did your arm or hand weakness resolve and return to normal?)
Sensory and motor assessment	While the patient is in hospital from post-block 2 hours, 6 hours, 12 hours, and 24 hours.	The affected lower limb will be measured.; Sensory assessment (Sensation to pin prick), rating from 0 (no sensation) to 10 (normal sensation); Motor assessment; * Straight leg raising achieved Ratings (Yes/ No); * Quadriceps power; Ratings: 0 - no muscle contraction; 1. - Move w/o gravity; 2. - Raise then drop down immediately; 3. - Raise against gravity w/o resistance; 4. - Raise against gravity w/some resistance; 5. - Raise against gravity w/ full resistance
quality of life (SF12v2)	at 6 weeks and at 3 and 6 months after surgery	Eight domains of SF-12v2 (HK) are measured on a scale ranging from 0 to 100. A higher domain score indicates a better HRQoL.
Identification Pain Questionnaire for Neuropathic Pain (ID-NeP)	at 6 weeks, 3 months and 6 months postoperatively	Neuropathic pain will be assessed using Identification Pain Questionnaire for Neuropathic Pain (ID-NeP), consisting of six items: "Yes" answers to questions 1-5 were given a score of 1, while "yes" answer to question 6 scored -1. "No" answers to questions 1-5 were given a score of 0, while "yes" answer to question 6 scored 0.
Knee Society Knee Function Score	at 6 weeks, 3 months and 6 months postoperatively	Knee Society Knee Function Score at 6 weeks, 3 months and 6 months postoperatively, from 0 to 100 with lower scores being indicative of worse knee conditions and higher scores being indicative of better knee conditions.
Chronic post-surgical pain	at 6 weeks, 3 months and 6 months postoperatively	The presence or absence of chronic post-surgical pain, pain scores if present.

Trial Locations

Locations (1)

The University of Hong Kong; 🇭🇰 Hong Kong, Hong Kong