Liposomal Bupivacaine vs Continuous Nerve Catheters for Below the Knee Amputations

NCT05140499 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: 1807862-1
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Through this pilot prospective trial, we aim to obtain preliminary data investigating the effectiveness of perineural catheters and liposomal bupivacaine, both currently accepted as standard care at Maine Medical Center, for the management of post-limb amputation pain. We will use the data that we collect to inform the design of a larger, appropriately powered study.

Conditions

Pain, Postoperative; Amputation

Outcome Measures

Primary Outcomes (1)

• Pain Assessed by Numerical Rating Scale (NRS)

  Average NRS pain scores (0-10, 0=no pain, 10=worst possible pain)

  72 hours post-operatively

Secondary Outcomes (4)

• Opioid Consumption

  72 hours post-operatively

• Post-operative Length of Stay

  Measured from surgical stop time to discharge time, an average of 5 days.

• Post-operative Pain Assessed by the Short Form McGill Pain Questionnaire-2 (SFMPQ-2)

  30 days following surgery

• Phantom Limb Pain Assessed Using Questions From the Trinity Amputation and Prosthesis Experiences Scales-Revised (TAPES-R)

  30 days following surgery

Study Arms (2)

Single Shot Perineural Popliteal Nerve Block

ACTIVE COMPARATOR

Single shot perineural popliteal nerve block injection of 10cc 13.3% liposomal bupivacaine combined with 15cc 0.50% bupivacaine hydrochloride within one hour prior to surgery

Drug: Liposomal bupivacaine

Continuous perineural popliteal nerve block catheter

ACTIVE COMPARATOR

Placement of continuous perineural popliteal nerve block catheter with injection of 30cc 0.5% bupivacaine within one hour prior to surgery, followed by continuous infusion of 10cc 0.3% ropivacaine (current standard practice) for at least 72 hours following surgery. Saphenous single shot 20cc 0.2

Drug: Bupivacaine Hydrochloride 0.5 % Injectable Solution

Interventions

Bupivacaine Hydrochloride 0.5 % Injectable Solution DRUG

Continuous nerve catheter

Also known as: conventional bupivacaine

Continuous perineural popliteal nerve block catheter

Liposomal bupivacaine DRUG

Popliteal nerve block

Also known as: Exparel

Single Shot Perineural Popliteal Nerve Block

Eligibility Criteria

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

You may qualify if:

• American Society of Anesthesiologists Physical Status Classification I-IV
• Scheduled for primary amputation or stump revision
• English speaking

You may not qualify if:

• Patients unable to cooperate or consent to the study
• Allergy to local anesthetics
• Existing infection at planned needle insertion site
• BMI \> 40kg/m2
• Patients with a history of coagulopathy
• Emergency amputations
• Contralateral amputations
• Patients with a substance use disorder diagnosis
• Patients on opioids \>90 morphine milligram equivalents (MME)/day

Sponsors & Collaborators

• Aurora Quaye: lead
• MaineHealth: collaborator

Study Sites (1)

Maine Medical Center

Portland, Maine, 04102, United States

Location

Related Publications (24)

• Neil MJE. Pain after amputation. BJA Education. 2016: 16(3):107-12.

  BACKGROUND

• Borg L, Howard SK, Kim TE, Steffel L, Shum C, Mariano ER. A comparison of strength for two continuous peripheral nerve block catheter dressings. Korean J Anesthesiol. 2016 Oct;69(5):506-509. doi: 10.4097/kjae.2016.69.5.506. Epub 2016 Jul 25.

  PMID: 27703632 BACKGROUND

• Borghi B, D'Addabbo M, White PF, Gallerani P, Toccaceli L, Raffaeli W, Tognu A, Fabbri N, Mercuri M. The use of prolonged peripheral neural blockade after lower extremity amputation: the effect on symptoms associated with phantom limb syndrome. Anesth Analg. 2010 Nov;111(5):1308-15. doi: 10.1213/ANE.0b013e3181f4e848. Epub 2010 Sep 29.

  PMID: 20881281 BACKGROUND

• Ilfeld BM. Continuous peripheral nerve blocks: a review of the published evidence. Anesth Analg. 2011 Oct;113(4):904-25. doi: 10.1213/ANE.0b013e3182285e01. Epub 2011 Aug 4.

  PMID: 21821511 BACKGROUND

• Ilfeld BM. Continuous peripheral nerve blocks in the hospital and at home. Anesthesiol Clin. 2011 Jun;29(2):193-211. doi: 10.1016/j.anclin.2011.04.003.

  PMID: 21620338 BACKGROUND

• Bergese SD, Ramamoorthy S, Patou G, Bramlett K, Gorfine SR, Candiotti KA. Efficacy profile of liposome bupivacaine, a novel formulation of bupivacaine for postsurgical analgesia. J Pain Res. 2012;5:107-16. doi: 10.2147/JPR.S30861. Epub 2012 May 1.

  PMID: 22570563 BACKGROUND

• Prabhakar A, Ward CT, Watson M, Sanford J, Fiza B, Moll V, Kaye RJ, Morgan Hall O, Cornett EM, Urman RD, Kaye AD. Liposomal bupivacaine and novel local anesthetic formulations. Best Pract Res Clin Anaesthesiol. 2019 Dec;33(4):425-432. doi: 10.1016/j.bpa.2019.07.012. Epub 2019 Jul 19.

  PMID: 31791561 BACKGROUND

• Davidovitch R, Goch A, Driesman A, Konda S, Pean C, Egol K. The Use of Liposomal Bupivacaine Administered With Standard Bupivacaine in Ankle Fractures Requiring Open Reduction Internal Fixation: A Single-Blinded Randomized Controlled Trial. J Orthop Trauma. 2017 Aug;31(8):434-439. doi: 10.1097/BOT.0000000000000862.

  PMID: 28430722 BACKGROUND

• Mazloomdoost D, Pauls RN, Hennen EN, Yeung JY, Smith BC, Kleeman SD, Crisp CC. Liposomal bupivacaine decreases pain following retropubic sling placement: a randomized placebo-controlled trial. Am J Obstet Gynecol. 2017 Nov;217(5):598.e1-598.e11. doi: 10.1016/j.ajog.2017.07.001. Epub 2017 Jul 8.

  PMID: 28694151 BACKGROUND

• Yan Z, Chen Z, Ma C. Liposomal bupivacaine versus interscalene nerve block for pain control after shoulder arthroplasty: A meta-analysis. Medicine (Baltimore). 2017 Jul;96(27):e7226. doi: 10.1097/MD.0000000000007226.

  PMID: 28682872 BACKGROUND

• Hussain N, Brull R, Sheehy B, Essandoh MK, Stahl DL, Weaver TE, Abdallah FW. Perineural Liposomal Bupivacaine Is Not Superior to Nonliposomal Bupivacaine for Peripheral Nerve Block Analgesia. Anesthesiology. 2021 Feb 1;134(2):147-164. doi: 10.1097/ALN.0000000000003651.

  PMID: 33372953 BACKGROUND

• Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006 May 13;367(9522):1618-25. doi: 10.1016/S0140-6736(06)68700-X.

  PMID: 16698416 BACKGROUND

• Richardson C, Glenn S, Nurmikko T, Horgan M. Incidence of phantom phenomena including phantom limb pain 6 months after major lower limb amputation in patients with peripheral vascular disease. Clin J Pain. 2006 May;22(4):353-8. doi: 10.1097/01.ajp.0000177793.01415.bd.

  PMID: 16691088 BACKGROUND

• Jensen TS, Krebs B, Nielsen J, Rasmussen P. Immediate and long-term phantom limb pain in amputees: incidence, clinical characteristics and relationship to pre-amputation limb pain. Pain. 1985 Mar;21(3):267-278. doi: 10.1016/0304-3959(85)90090-9.

  PMID: 3991231 BACKGROUND

• Madabhushi L, Reuben SS, Steinberg RB, Adesioye J. The efficacy of postoperative perineural infusion of bupivacaine and clonidine after lower extremity amputation in preventing phantom limb and stump pain. J Clin Anesth. 2007 May;19(3):226-9. doi: 10.1016/j.jclinane.2006.07.008.

  PMID: 17531734 BACKGROUND

• Jahangiri M, Jayatunga AP, Bradley JW, Dark CH. Prevention of phantom pain after major lower limb amputation by epidural infusion of diamorphine, clonidine and bupivacaine. Ann R Coll Surg Engl. 1994 Sep;76(5):324-6.

  PMID: 7979074 BACKGROUND

• Lambert Aw, Dashfield Ak, Cosgrove C, Wilkins Dc, Walker Aj, Ashley S. Randomized prospective study comparing preoperative epidural and intraoperative perineural analgesia for the prevention of postoperative stump and phantom limb pain following major amputation. Reg Anesth Pain Med. 2001 Jul-Aug;26(4):316-21. doi: 10.1053/rapm.2001.23934.

  PMID: 11464349 BACKGROUND

• Nikolajsen L, Ilkjaer S, Christensen JH, Kroner K, Jensen TS. Randomised trial of epidural bupivacaine and morphine in prevention of stump and phantom pain in lower-limb amputation. Lancet. 1997 Nov 8;350(9088):1353-7. doi: 10.1016/S0140-6736(97)06315-0.

  PMID: 9365449 BACKGROUND

• Nikolajsen L, Ilkjaer S, Jensen TS. Effect of preoperative extradural bupivacaine and morphine on stump sensation in lower limb amputees. Br J Anaesth. 1998 Sep;81(3):348-54. doi: 10.1093/bja/81.3.348.

  PMID: 9861117 BACKGROUND

• Morey TE, Giannoni J, Duncan E, Scarborough MT, Enneking FK. Nerve sheath catheter analgesia after amputation. Clin Orthop Relat Res. 2002 Apr;(397):281-9. doi: 10.1097/00003086-200204000-00032.

  PMID: 11953619 BACKGROUND

• Dworkin RH, Turk DC, Revicki DA, Harding G, Coyne KS, Peirce-Sandner S, Bhagwat D, Everton D, Burke LB, Cowan P, Farrar JT, Hertz S, Max MB, Rappaport BA, Melzack R. Development and initial validation of an expanded and revised version of the Short-form McGill Pain Questionnaire (SF-MPQ-2). Pain. 2009 Jul;144(1-2):35-42. doi: 10.1016/j.pain.2009.02.007. Epub 2009 Apr 7.

  PMID: 19356853 BACKGROUND

• Gallagher P, MacLachlan M. Development and psychometric evaluation of the Trinity Amputation and Prosthesis Experience Scales (TAPES). Rehabilitation Psychology. 2000: 45(2), 130-154.

  BACKGROUND

• Jensen MP, Castarlenas E, Tome-Pires C, de la Vega R, Sanchez-Rodriguez E, Miro J. The Number of Ratings Needed for Valid Pain Assessment in Clinical Trials: Replication and Extension. Pain Med. 2015 Sep;16(9):1764-72. doi: 10.1111/pme.12823. Epub 2015 Jul 14.

  PMID: 26178637 BACKGROUND

• Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharmaceutical Statistics. 2005;4(4):287-91.

  BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Bupivacaine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Results Point of Contact

• Title: Clinical Trials Director
• Organization: MaineHealth Institute for Research

MHIR_INFO@mainehealth.org

207-396-8100

Study Officials

• Aurora Quaye, MD

  MaineHealth

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Vice Chair of Research, Department of Anesthesiology and Perioperative Medicine, Maine Medical Center

Study Record Dates

• First Submitted: October 25, 2021
• First Posted: December 1, 2021
• Study Start: August 15, 2022
• Primary Completion: November 20, 2025
• Study Completion: December 23, 2025
• Last Updated: January 27, 2026
• Results First Posted: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)