Pain, PostoperativePhase 4NCT05140499
Liposomal Bupivacaine vs Continuous Nerve Catheters for Below the Knee Amputations
A Phase 4 study testing Liposomal bupivacaine and Bupivacaine Hydrochloride 0.5 % Injectable Solution in people with Pain, Postoperative and Amputation, run by Aurora Quaye at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain, Postoperative, Amputation
- What is being tested?
- Liposomal bupivacaine and Bupivacaine Hydrochloride 0.5 % Injectable Solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Aug 2022to 23 Dec 2025
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- American Society of Anesthesiologists Physical Status Classification I-IV
- Scheduled for primary amputation or stump revision
- English speaking
Who cannot join
- 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
Show all 9Show fewer
- Contralateral amputations
- Patients with a substance use disorder diagnosis
- Patients on opioids >90 morphine milligram equivalents (MME)/day
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Pain, Postoperative, Amputation
- Being tested
- Liposomal bupivacaine, Bupivacaine Hydrochloride 0.5 % Injectable Solution
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liposomal bupivacaineDrug
Also called Exparel
Popliteal nerve block
Bupivacaine Hydrochloride 0.5 % Injectable SolutionDrug
Also called conventional bupivacaine
Continuous nerve catheter
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Bupivacaine Hydrochloride 0.5 % Injectable Solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain Assessed by Numerical Rating Scale (NRS)
Average NRS pain scores (0-10, 0=no pain, 10=worst possible pain)
Measured: 72 hours post-operatively
Secondary outcomes (4)
Opioid Consumption
Total amount of opioid medication given, in morphine milligram equivalents
Measured: 72 hours post-operatively
Post-operative Length of Stay
Post-operative length of stay in hours
Measured: 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)
Total SFMPQ-2 score (low score of 0, no pain to a high score of 220, worst possible pain)
Measured: 30 days following surgery
Phantom Limb Pain Assessed Using Questions From the Trinity Amputation and Prosthesis Experiences Scales-Revised (TAPES-R)
Phantom Limb Pain was measured using questions 4 and 5 from Part II of the TAPES-R (scores can range from 0, no pain, to 22, severe pain)
Measured: 30 days following surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2021
- Study start15 Aug 2022
- Primary completion20 Nov 2025
- Study completion23 Dec 2025
Why it stopped: Difficulty with enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for Pain, PostoperativeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aurora Quaye
- Sponsor type
- University, hospital or other
- Collaborators
- MaineHealth
- Responsible party
- Sponsor-investigator, Aurora Quaye, MaineHealth
- Investigators
- Aurora Quaye, MD, Principal investigator, MaineHealth
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05140499
- Sponsor's protocol ID
- 1807862-1
- Status last verified
- Jan 2026
- First submitted
- 25 Oct 2021
- Last updated
- 27 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Neil MJE. Pain after amputation. BJA Education. 2016: 16(3):107-12.
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.
PubMed 27703632Borghi 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.
PubMed 20881281Ilfeld 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.
PubMed 21821511Ilfeld 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.
PubMed 21620338Bergese 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.
PubMed 22570563Prabhakar 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.
PubMed 31791561Davidovitch 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.
PubMed 28430722Mazloomdoost 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.
PubMed 28694151Yan 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.
PubMed 28682872Hussain 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.
PubMed 33372953Kehlet 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.
PubMed 16698416Richardson 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.
PubMed 16691088Jensen 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.
PubMed 3991231Madabhushi 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.
PubMed 17531734
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05140499
- Acronym / sponsor ID
- 1807862-1
- Conditions
- Pain, Postoperative, Amputation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty with enrollment
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Aurora QuayeUniversity, hospital or other
- Collaborators
- MaineHealth
- Study start
- 15 Aug 2022 (actual)
- Primary completion
- 20 Nov 2025 (actual)
- Study completion
- 23 Dec 2025 (actual)
- First posted
- 1 Dec 2021 (actual)
- Results
- Posted 27 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Single Shot Perineural Popliteal Nerve Block | Active comparator | Drug: Liposomal bupivacaineSingle 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 |
| Continuous perineural popliteal nerve block catheter | Active comparator | Drug: Bupivacaine Hydrochloride 0.5 % Injectable SolutionPlacement 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- American Society of Anesthesiologists Physical Status Classification I-IV
- Scheduled for primary amputation or stump revision
- English speaking
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liposomal bupivacaineAlso: ExparelPopliteal nerve block | Drug | Single Shot Perineural Popliteal Nerve Block |
| Bupivacaine Hydrochloride 0.5 % Injectable SolutionAlso: conventional bupivacaineContinuous nerve catheter | Drug | Continuous perineural popliteal nerve block catheter |
Primary outcome
Pain Assessed by Numerical Rating Scale (NRS)
Time frame: 72 hours post-operatively
Average NRS pain scores (0-10, 0=no pain, 10=worst possible pain)
4 secondary outcomes
Opioid Consumption
Time frame: 72 hours post-operatively
Post-operative Length of Stay
Time frame: 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)
Time frame: 30 days following surgery
Phantom Limb Pain Assessed Using Questions From the Trinity Amputation and Prosthesis Experiences Scales-Revised (TAPES-R)
Time frame: 30 days following surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundNeil MJE. Pain after amputation. BJA Education. 2016: 16(3):107-12.
- Background: PubMed 27703632Borg 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.
- Background: PubMed 20881281Borghi 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.
- Background: PubMed 21821511Ilfeld 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.
- Background: PubMed 21620338Ilfeld 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.
- Background: PubMed 22570563Bergese 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.
- Background: PubMed 31791561Prabhakar 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.
- Background: PubMed 28430722Davidovitch 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.
- Background: PubMed 28694151Mazloomdoost 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.
- Background: PubMed 28682872Yan 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.
- Background: PubMed 33372953Hussain 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.
- Background: PubMed 16698416Kehlet 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aurora Quaye, MD principal investigator
MaineHealth
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Liposomal bupivacaine and Bupivacaine Hydrochloride 0.5 % Injectable Solution in people with Pain, Postoperative and Amputation, run by Aurora Quaye at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain Assessed by Numerical Rating Scale (NRS) (time frame: 72 hours post-operatively). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05140499, which also lists 24 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2026.