Clinical trial NCT05140499: Liposomal Bupivacaine vs Continuous Nerve Catheters for Below the Knee Amputations
Official title: A Prospective, Randomized Trial of Liposomal Bupivacaine Compared to Continuous Nerve Catheters on Pain Control and Post-Operative Opioid Use in Receiving Popliteal Nerve Blocks for Below the Knee Amputation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Pain, Postoperative
Amputation
Lead sponsor: MaineHealth
Sponsor class: OTHER
Collaborators: name: MaineHealth
First posted: 2021-12-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Detailed description: Lower extremity amputation is a common surgical procedure often due to limb ischemia or complications related to diabetes mellitus. Managing postoperative pain can be quite challenging in this patient population and persistent post-surgical pain is not uncommon. Peripheral nerve catheters (PNCs) that deliver a continuous infusion of local anesthetic have been shown to provide analgesic benefit dependent upon infusion duration and in the absence of catheter malfunction. Unfortunately, PNCs can be difficult to place and rates of dislodgement are estimated at 30%. Single shot regional nerve blocks using liposomal bupivacaine are much easier to perform than PNCs and can provide up to 72 hours of pain relief, eliminating the need for catheter placement. To date, no study has investigated the effects of liposomal bupivacaine compared to PNCs for post-surgical pain control. In this pilot study, we intend to compare pain scores, opioid consumption, and length of stay in patients randomized to both treatment strategies. We also intend to conduct an exploratory analysis investigating incidence of phantom limb pain one month following surgery. Our results will inform the design of a larger powered study to investigate treatment effects.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Pain assessed by Numerical Rating Scale (NRS)
timeFrame: 72 hours post-operatively
Secondary outcomes:
measure: Opioid Consumption
timeFrame: 72 hours post-operatively
measure: Post-operative Length of Stay
timeFrame: Measured from surgical stop time to discharge time, an average of 5 days.
measure: Post-operative Pain assessed by the Short Form McGill Pain Questionnaire-2 (SFMPQ-2)
timeFrame: 30 days following surgery
measure: Phantom Limb Pain assessed using questions from the Trinity Amputation and Prosthesis Experiences Scales-Revised (TAPES-R)
timeFrame: 30 days following surgery
Other outcomes:
Locations:
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
Study officials:
affiliation: MaineHealth
name: Ryan Mountjoy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Neil MJE. Pain after amputation. BJA Education. 2016: 16(3):107-12.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Gallagher P, MacLachlan M. Development and psychometric evaluation of the Trinity Amputation and Prosthesis Experience Scales (TAPES). Rehabilitation Psychology. 2000: 45(2), 130-154.
citation: 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.
citation: Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharmaceutical Statistics. 2005;4(4):287-91.