Clinical Observation of Bupivacaine Liposome for Lower Extremity Nerve Block

Clinical Observation of Bupivacaine Liposome for Lower Extremity Femoral Nerve Block

This prospective, sequential dose-finding clinical observational study aims to estimate the median effective concentration (EC50) and the 95% effective concentration (EC95) of liposomal bupivacaine for ultrasound-guided femoral nerve block. Sensory and motor block endpoints are evaluated separately at 30 minutes after block placement using a modified up-and-down (sequential allocation) design, with trial termination after eight reversal points.

Study Overview

• Status: Completed
• Conditions: Knee Arthroscopic Surgery; Patients Eligible for Elective Lower Extremity Femoral Nerve Surgery
• Intervention / Treatment: Drug: Liposomal bupivacaine, 266mg

Detailed Description

This prospective clinical observational, sequential dose-finding study is designed to determine the effective concentrations of liposomal bupivacaine for ultrasound-guided femoral nerve block in patients undergoing lower limb surgery or related procedures.

All patients receive ultrasound-guided femoral nerve block performed by an experienced anesthesiologist using a standardized technique. A fixed injection volume of liposomal bupivacaine is administered, while the drug concentration is adjusted according to a modified up-and-down sequential method. The concentration for each subsequent participant is determined based on the response of the preceding participant. Following a positive response, the concentration is decreased; following a negative response, the concentration is increased by a pre-specified step size. The study is terminated after eight reversal points (crossovers) are observed.

To independently characterize sensory and motor block dose-response relationships, participants are allocated into two endpoint-specific observation groups:

Sensory block group

Sensory function in the femoral nerve distribution is assessed 30 minutes after block placement using standardized sensory testing. Complete loss of sensation at 30 minutes is defined as a positive response, while preserved sensation is defined as a negative response.

Motor block group

Motor function of the quadriceps muscle is evaluated 30 minutes after block placement using a standardized motor strength assessment. The successful (positive) quadriceps motor block is defined as a decrease of ≥1 grade in the muscle strength of the quadriceps compared with that before the block.

The primary objective of this study is to estimate the EC50 and EC95 of liposomal bupivacaine for:femoral nerve sensory blockade, and femoral nerve motor blockade, based on sequential allocation data and appropriate dose-response modeling.

Secondary objectives include describing the differential sensory-motor block profile of liposomal bupivacaine and evaluating its clinical feasibility and safety for femoral nerve block applications. All patients are monitored for block-related adverse events, including signs of local anesthetic systemic toxicity, nerve injury, and other complications throughout the perioperative period.

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hainan
    • Haikou, Hainan, China
      • Department of Anesthesiology,the Second Affiliated Hospital of Hainan Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 18 to 85 years
• Scheduled for elective unilateral lower limb surgery
• Unilateral ultrasound-guided femoral nerve block clinically indicated as part of routine perioperative anesthesia and analgesia management
• Ability to clearly distinguish between the blocked (operated) limb and the contralateral (non-blocked) limb for sensory and pain assessments
• Ability to understand the study procedures and provide written informed consent
• Ability to cooperate with sensory and motor assessments, including visual analog scale (VAS) scoring and quadriceps muscle strength testing

Exclusion Criteria:

• Known allergy or hypersensitivity to bupivacaine, amide-type local anesthetics, or any component of liposomal bupivacaine
• Infection at or near the planned injection site
• Coagulopathy or clinically significant bleeding disorder, or anticoagulant/antiplatelet therapy incompatible with peripheral nerve block
• Pre-existing neurological deficits, neuropathy, or motor weakness affecting either lower limb that could interfere with sensory or motor assessments
• Severe hepatic dysfunction or other conditions that increase the risk of local anesthetic systemic toxicity
• Pregnancy or breastfeeding
• Emergency surgery
• Inability to complete study assessments or comply with study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ultrasound-guided femoral nerve block with liposomal bupivacaine; Participants receive ultrasound-guided femoral nerve block with liposomal bupivacaine administered at varying concentrations using a modified up-and-down sequential dose-finding design. Sensory and motor block responses are assessed 30 minutes after block placement to estimate EC50 and EC95.	Drug: Liposomal bupivacaine, 266mg; Liposomal bupivacaine administered for ultrasound-guided femoral nerve block at varying concentrations using a modified up-and-down sequential dose-finding design.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EC50 and EC95 for femoral nerve sensory block	The median effective concentration (EC50) and the 95% effective concentration (EC95) of liposomal bupivacaine for ultrasound-guided femoral nerve sensory blockade are estimated using a modified up-and-down sequential dose-finding design. Sensory block is assessed 30 minutes after block placement in the femoral nerve distribution on the blocked side, including the anterior thigh (anterior femoral cutaneous nerve territory) and the medial aspect of the lower leg (saphenous nerve territory). Sensory testing is performed using pinprick testing and/or cold stimulation with an ether-soaked cotton swab, with the contralateral non-blocked limb used as an internal control. Sensory block is graded as follows: 0 = no block (sensation identical to the non-blocked limb); 1 = partial block (reduced sensation); 2 = complete block (absence of pain sensation). A positive sensory response is defined as a sensory block score of 2.	30 minutes after femoral nerve block placement
EC50 and EC95 for femoral nerve motor block	The median effective concentration (EC50) and the 95% effective concentration (EC95) of liposomal bupivacaine for ultrasound-guided femoral nerve motor blockade, estimated using a modified up-and-down sequential dose-finding design. Motor function is evaluated immediately by assessing quadriceps muscle strength. Patients are instructed to perform a straight leg raise in the supine position or actively extend the knee. Muscle strength is graded using the Medical Research Council (MRC) scale (0-5). The successful (positive) quadriceps motor block is defined as a decrease of ≥1 grade in the muscle strength of the quadriceps compared with that before the block.	30 minutes after femoral nerve block placement

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative movement-evoked pain assessed by VAS	Movement-evoked pain is assessed using the Visual Analog Scale (VAS, 0-10). VAS scores are recorded during active movement of the operated limb on postoperative day 1 and postoperative day 2 to evaluate pain associated with mobilization following femoral nerve block.	Postoperative day 1 and day 2
Quadriceps muscle strength after surgery	Quadriceps muscle strength on the operated side is evaluated using the Medical Research Council (MRC) muscle strength scale (0-5). Assessments are performed on postoperative day 1 and postoperative day 2 to evaluate recovery of motor function following femoral nerve block.	Postoperative day 1 and day 2
Length of hospital stay	Length of hospital stay is defined as the number of days from the date of surgery to the date of hospital discharge.	From the date of surgery until hospital discharge, assessed up to 30 days postoperatively.
Time to first ambulation after surgery	Time to first ambulation is defined as the time interval from the end of surgery to the patient's first out-of-bed ambulation with or without assistance.	From the end of surgery until the first out-of-bed ambulation, assessed up to 72 hours postoperatively.
Intraoperative heart rate	Intraoperative heart rate is continuously monitored and recorded during surgery to assess intraoperative physiological stability.	From skin incision to the end of surgery, assessed continuously during the intraoperative period.
Intraoperative mean arterial pressure	Intraoperative mean arterial pressure is continuously monitored and recorded during surgery to assess intraoperative hemodynamic stability.	From skin incision to the end of surgery, assessed continuously during the intraoperative period.
Postoperative Resting pain intensity assessed by VAS	Postoperative Resting pain intensity is assessed using the Visual Analog Scale (VAS, 0-10, where 0 indicates no pain and 10 indicates the worst imaginable pain). VAS scores will be recorded while the patient is at rest on postoperative day 1 and postoperative day 2 to evaluate pain at rest following femoral nerve block. A higher score indicates more severe pain.	postoperative day 1 and day 2

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events related to femoral nerve block	Adverse events potentially related to ultrasound-guided femoral nerve block or liposomal bupivacaine administration are monitored and recorded. These include, but are not limited to, local anesthetic systemic toxicity, nerve injury, infection, hematoma, and other block-related or drug-related complications.	From femoral nerve block placement until hospital discharge, assessed up to 30 days postoperatively.

Collaborators and Investigators

• Sponsor: Hainan Medical College
• Collaborators: The Second Affiliated Hospital of Hainan Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2026
• Primary Completion (Actual): March 31, 2026
• Study Completion (Actual): April 1, 2026

Study Registration Dates

• First Submitted: January 8, 2026
• First Submitted That Met QC Criteria: January 16, 2026
• First Posted (Actual): January 26, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: HUMU2H-DCOEOP-CN-2025; No.823RC592 (Other Grant/Funding Number: Hainan Provincial Natural Science Foundation of China)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No