Combined Local Anesthetic Blockade and Neuromodulation vs Local Anesthetic Blockade Only for Analgesia After Below-knee Amputation: RCT

A Randomized Clinical Trial Comparing the Analgesic Efficacy of Combined Local Anesthetic Blockade and Neuromodulation (Hybrid Technique) Versus Local Anesthetic Blockade Only for Analgesia After Below-knee Amputation

This multi-site clinical trial aims to assess the efficacy and safety of combining peripheral nerve stimulation with local anesthetic nerve blockade compared to the standard of care, i.e., local anesthetic blockade only using safe stimulation parameters in a condition associated with high postoperative pain state, i.e. a patient undergoing lower limb amputation.

Study Overview

• Status: Not yet recruiting
• Conditions: Amputation
• Intervention / Treatment: Device: Ropivacaine 0.2% + nerve stimulator set; Drug: Ropivacaine 0.2%

Detailed Description

The primary aim of this pilot trial is to evaluate the feasibility, safety, and analgesic efficacy of the hybrid technique (combined PNS and LA-based PNB) compared to that of PNB during the hospital course in patients undergoing below-knee amputations. The secondary aims are to estimate analgesia and opioid-sparing effects at later timepoints of 3, 6, and 12 months following the surgery.

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ksenia (kasimova), MD; Phone Number: 6507889458; Email: kasimova@stanford.edu
• Study Contact Backup: Name: Ban CH Tsui, MD; Phone Number: 6502009107; Email: bantsui@stanford.edu

Study Locations

• Canada
  • Edmonton, Canada
    • University of Alberta
    • Contact: Vivian Ip, MD
• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University
      • Contact: Ban CH Tsui, MD; Phone Number: 650-200-9107; Email: bantsui@stanford.edu
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
      • Contact: Hari Kalagara, MD
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
      • Contact: Rakesh Sondekoppam, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients at least 18 years of age
• Undergoing below-knee amputation

Exclusion Criteria:

• Chronic opioid use (daily use within the two weeks before surgery and duration of use of more than four weeks of > 30 mg of oxycodone per day or > 50 of morphine milligrams per day)
• Neuromuscular deficit of the target nerve(s)
• Compromised immune system or concurrent risk of infection based on medical history (e.g., immunosuppressive therapies such as chemotherapy, radiation, sepsis, infection).
• Implanted spinal cord stimulator, cardiac pacemaker/defibrillator, deep brain stimulator, or another implantable neurostimulator whose stimulus current pathway may overlap
• History of bleeding disorder or chronic antiplatelet or anticoagulation therapies (other than aspirin) that require to be restarted within the first three postoperative days
• Allergy to study medications or devices (including occlusive dressings, bandages, tape, etc.)
• Incarceration
• Pregnancy
• Chronic pain for more than three months of any severity in an anatomic location other than the surgical site
• Anxiety disorder
• History of substance abuse
• Inability to consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group Hybrid block; Continuous local anesthetic infusion through the nerve block catheter and peripheral nerve stimulation.	Device: Ropivacaine 0.2% + nerve stimulator set; Patients will receive a continuous local anesthetic (LA) infusion through the popliteal sciatic nerve block catheter using an infusion of ropivacaine 0.2% at a rate of 8-12 ml/h for at least 3 postoperative days. In addition, patients will receive a low-frequency peripheral nerve stimulation (PNS) via a nerve stimulator set to the pre-determined setting of adequate clinical response (determined in the preoperative area).
Active Comparator: Group LA block; Continuous local anesthetic infusion through the nerve block catheter.	Drug: Ropivacaine 0.2%; Patients will receive a continuous local anesthetic infusion through the popliteal sciatic nerve block catheter using an infusion of ropivacaine 0.2% at a rate of 8-12 ml/h for at least 3 postoperative days. In addition, patients will have an inactive PNS button for the purposes of blinding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain scores	Decrease in the proportional incidence of severe or intolerable pain scores (11-point numerical rating scale (NRS) from 0-10, 0 signifying no pain, 10 signifying the worse pain)	First 24 postoperative hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analgesic consumption	Cumulative rescue and breakthrough analgesic consumption	At 24, 48, and 72 postoperative hours
Quality of recovery (QoR-15)	Survey based on patient-reported outcomes. There are 15 questions based on a scale of 0-10, 0 signifying the worst outcome, 10 signifying the best, for a score range of 0-150.	At postoperative clinic visit (around 1-2 weeks)
Pain scores	Static and dynamic pain scores (11-point numerical rating scale (NRS) from 0-10, 0 signifying no pain, 10 signifying the worse pain)	At 12 hour time intervals over the 72 hours
Brief Pain Inventory - short form	A self-reported scale that assesses both the severity of pain and impact of pain on daily functioning, each question assessed on an 11-point scale, where 0 represents the best outcome and 10 - the worst outcome. The score range is 0-110.	During the preoperative assessment and at the 3 and 6 months postoperative assessments.
Phantom limb pain	The incidence of phantom limb and residual limb pain in both groups	At 1 week, three months, 6 months and 1 year
Adverse events	Block and opioid-related adverse events	Duration of postoperative recovery (typically 1-2 weeks)
Time to ambulation	Number of post-operative days until ambulation	Duration of postoperative recovery (typically 1-2 weeks)
Hospital length of stay	Number of post-operative days spent in hospital	Duration of postoperative recovery (typically 1-2 weeks)

Collaborators and Investigators

• Sponsor: Stanford University

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 9, 2024
• First Submitted That Met QC Criteria: April 30, 2025
• First Posted (Actual): May 9, 2025

Study Record Updates

• Last Update Posted (Actual): May 9, 2025
• Last Update Submitted That Met QC Criteria: April 30, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: neuromodulation; peripheral nerve stimulation; post-amputation pain; peripheral nerve block; below-knee amputation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Ropivacaine
• Other Study ID Numbers: 73646

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: Yes