LIBERATE - LIposomal Bupivacaine vERsus Adjuncts in Total shouldErs

NCT03887650 | Completed Phase 4 Results FDA Drug

• 1 other identifier: HHC-2018-0231
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a single-center, prospective, randomized controlled cross-sectional study comparing interscalene brachial plexus block with liposomal bupivacaine versus bupivacaine with epinephrine and PF dexamethasone in patients undergoing primary shoulder arthroplasty. Primary endpoint will be total opioid consumption in the first three post-operative days.

Conditions

Post-operative Pain; Total Shoulder Arthroplasty; Osteoarthritis of the Shoulder; Pain Management

Keywords

Brachial Plexus; Liposomal Bupivacaine; Dexamethasone; Interscalene; Bupivacaine; Shoulder Arthroplasty; Regional anesthesia; Exparel

Outcome Measures

Primary Outcomes (1)

• Total Opioid Consumption

  Total opioids used for the first 120 postoperative hours after TSA, standardized to morphine milligram equivalents (MMEs)

  Up to 120 postoperative hours

Secondary Outcomes (8)

• Time to First Opioid Medication

  from the time of the block injection until discharge, assessed up to 72 postoperative hours.

• Pain Assessment at Post Anesthesia Care Unit (PACU)-96 Postoperative Hours

  24, 24-48, 48-72, and 72-96 hours postoperation, and at day 60

• Hospital Length-of-stay

  From the date of admission until discharge, assessed up to 72 hours.

• Assessment of Patient Overall Satisfaction With Pain Control

  POD4 - 60 days

• Incidence of Distress From Block Numbness

  At PACU and Postoperative day 2

Other Outcomes (1)

• Total Amount of Opioid Consumed During the Indicated Time Periods

  0-24, 24-48, 48-72, and 72-120 postoperative hours.

Study Arms (2)

Liposomal Bupivacaine 1.3%

EXPERIMENTAL

10mL Liposomal Bupivacaine 1.3% (133 mg) mixed with 10mL of 0.5% Bupivacaine (total volume 20mL) in single injection interscalene brachial plexus block

Drug: Liposomal Bupivicaine 1.3%

Bupivacaine 0.5% with Adjuncts

ACTIVE COMPARATOR

20mL 0.5% Bupivacaine with 5 mg PF dexamethasone and 5 mcg epinephrine (total volume 20.5mL) in single injection interscalene brachial plexus block

Drug: Bupivacaine 0.5%

Interventions

Liposomal Bupivicaine 1.3% DRUG

10mL Liposomal Bupivacaine 1.3% (133 mg) mixed with 10mL of 0.5% Bupivacaine (total volume 20mL) in single injection interscalene brachial plexus block

Liposomal Bupivacaine 1.3%

Bupivacaine 0.5% DRUG

20mL 0.5% Bupivacaine with 5 mg PF dexamethasone and 5 mcg epinephrine (total volume 20.5mL) in single injection interscalene brachial plexus block

Also known as: epinephrine, dexamethasone preservative-free

Bupivacaine 0.5% with Adjuncts

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient age \>18 years;
• Lack of language barrier;
• Informed consent obtained;
• Presenting for primary total shoulder arthroplasty (TSA), both anatomic and reverse, by a specialty-trained surgeon;
• American Society of Anesthesiology (ASA) physical status score I- III

You may not qualify if:

• Presence of a language barrier;
• Inability to complete telephone and/or paper questionnaire;
• Lack of consent;
• Allergy to local anesthetic;
• Chronic pain syndrome and/or preoperative opioid use \> 50 MME per day (including extended-release formulations and methadone);
• Preoperative consultation to chronic pain service;
• History of (\<3 months) or current substance abuse, including any illicit drugs or excessive alcohol consumption as defined by the Office of Disease Prevention and Health Promotion (4 or more drinks per day or 8 or more drinks per week for women and 5 or more drinks per day or 15 or more drinks per week for men);
• Baseline peripheral neuropathy of the brachial plexus;
• Contraindication to receiving single shot peripheral nerve blockade; including antithrombotic medications as per most recent American Society of Regional - - -Anesthesiology (ASRA) guidelines 17 , coagulopathy or coagulation disorder, or infection at injection site;
• Severe chronic obstructive pulmonary disease (COPD) or other significant pulmonary disease where interscalene nerve block would be contraindicated due to concern for respiratory failure from phrenic nerve palsy;
• Weight \< 45 kg, given concern for local anesthetic toxicity at dosages given for the study; ASA score IV-V;
• Revision arthroplasty;
• Anatomic abnormality that limits or prevents the patient from receiving an interscalene nerve block;
• Pregnant, nursing, or planning to become pregnant during the study or within 1 month after the shoulder replacement surgery

Sponsors & Collaborators

• Hartford Hospital: lead

Study Sites (1)

The Bone and Joint Institute at Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Related Publications (12)

• Brummett CM, Waljee JF, Goesling J, Moser S, Lin P, Englesbe MJ, Bohnert ASB, Kheterpal S, Nallamothu BK. New Persistent Opioid Use After Minor and Major Surgical Procedures in US Adults. JAMA Surg. 2017 Jun 21;152(6):e170504. doi: 10.1001/jamasurg.2017.0504. Epub 2017 Jun 21.

  PMID: 28403427 BACKGROUND

• Vieira PA, Pulai I, Tsao GC, Manikantan P, Keller B, Connelly NR. Dexamethasone with bupivacaine increases duration of analgesia in ultrasound-guided interscalene brachial plexus blockade. Eur J Anaesthesiol. 2010 Mar;27(3):285-8. doi: 10.1097/EJA.0b013e3283350c38.

  PMID: 20009936 BACKGROUND

• Movafegh A, Razazian M, Hajimaohamadi F, Meysamie A. Dexamethasone added to lidocaine prolongs axillary brachial plexus blockade. Anesth Analg. 2006 Jan;102(1):263-7. doi: 10.1213/01.ane.0000189055.06729.0a.

  PMID: 16368840 BACKGROUND

• Parrington SJ, O'Donnell D, Chan VW, Brown-Shreves D, Subramanyam R, Qu M, Brull R. Dexamethasone added to mepivacaine prolongs the duration of analgesia after supraclavicular brachial plexus blockade. Reg Anesth Pain Med. 2010 Sep-Oct;35(5):422-6. doi: 10.1097/AAP.0b013e3181e85eb9.

  PMID: 20814282 BACKGROUND

• Rasmussen SB, Saied NN, Bowens C Jr, Mercaldo ND, Schildcrout JS, Malchow RJ. Duration of upper and lower extremity peripheral nerve blockade is prolonged with dexamethasone when added to ropivacaine: a retrospective database analysis. Pain Med. 2013 Aug;14(8):1239-47. doi: 10.1111/pme.12150. Epub 2013 Jun 11.

  PMID: 23755801 BACKGROUND

• McLaughlin DC, Cheah JW, Aleshi P, Zhang AL, Ma CB, Feeley BT. Multimodal analgesia decreases opioid consumption after shoulder arthroplasty: a prospective cohort study. J Shoulder Elbow Surg. 2018 Apr;27(4):686-691. doi: 10.1016/j.jse.2017.11.015. Epub 2018 Jan 3.

  PMID: 29305103 BACKGROUND

• Candiotti K. Liposomal bupivacaine: an innovative nonopioid local analgesic for the management of postsurgical pain. Pharmacotherapy. 2012 Sep;32(9 Suppl):19S-26S. doi: 10.1002/j.1875-9114.2012.01183.x.

  PMID: 22956491 BACKGROUND

• Abildgaard JT, Lonergan KT, Tolan SJ, Kissenberth MJ, Hawkins RJ, Washburn R 3rd, Adams KJ, Long CD, Shealy EC, Motley JR, Tokish JM. Liposomal bupivacaine versus indwelling interscalene nerve block for postoperative pain control in shoulder arthroplasty: a prospective randomized controlled trial. J Shoulder Elbow Surg. 2017 Jul;26(7):1175-1181. doi: 10.1016/j.jse.2017.03.012. Epub 2017 May 4.

  PMID: 28479257 BACKGROUND

• Hannan CV, Albrecht MJ, Petersen SA, Srikumaran U. Liposomal Bupivacaine vs Interscalene Nerve Block for Pain Control After Shoulder Arthroplasty: A Retrospective Cohort Analysis. Am J Orthop (Belle Mead NJ). 2016 Nov/Dec;45(7):424-430.

  PMID: 28005096 BACKGROUND

• Wang K, Zhang HX. Liposomal bupivacaine versus interscalene nerve block for pain control after total shoulder arthroplasty: A systematic review and meta-analysis. Int J Surg. 2017 Oct;46:61-70. doi: 10.1016/j.ijsu.2017.08.569. Epub 2017 Aug 24.

  PMID: 28843463 BACKGROUND

• Schroer WC, Diesfeld PG, LeMarr AR, Morton DJ, Reedy ME. Does Extended-Release Liposomal Bupivacaine Better Control Pain Than Bupivacaine After Total Knee Arthroplasty (TKA)? A Prospective, Randomized Clinical Trial. J Arthroplasty. 2015 Sep;30(9 Suppl):64-7. doi: 10.1016/j.arth.2015.01.059. Epub 2015 Jun 3.

  PMID: 26117072 BACKGROUND

• Vandepitte C, Kuroda M, Witvrouw R, Anne L, Bellemans J, Corten K, Vanelderen P, Mesotten D, Leunen I, Heylen M, Van Boxstael S, Golebiewski M, Van de Velde M, Knezevic NN, Hadzic A. Addition of Liposome Bupivacaine to Bupivacaine HCl Versus Bupivacaine HCl Alone for Interscalene Brachial Plexus Block in Patients Having Major Shoulder Surgery. Reg Anesth Pain Med. 2017 May/Jun;42(3):334-341. doi: 10.1097/AAP.0000000000000560.

  PMID: 28157791 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative; Agnosia

Interventions

Epinephrine

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Limitations and Caveats

Opioid consumption was subjected to patient recall and reporting bias. Patients were advised by surgery clinics to limit opioid intake postoperatively, which might indirectly limit opioid use and made it more difficult to show a difference. The study was double-blinded, the anesthesiologists who performed the block, were unblinded due to the difference in the physical appearance of the study drugs.

Results Point of Contact

• Title: Dr. Kevin Finkel
• Organization: Hartford Hospital

Kevin.Finkel@hhchealth.org

860-972-1778

Study Officials

• Kevin Finkel, MD

  Hartford Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: single-center, prospective, randomized controlled cross-sectional study

Study Record Dates

• First Submitted: March 21, 2019
• First Posted: March 25, 2019
• Study Start: March 11, 2019
• Primary Completion: January 11, 2022
• Study Completion: March 8, 2022
• Last Updated: September 15, 2023
• Results First Posted: September 15, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)