Liposomal Bupivacaine in Simultaneous Bilateral Total Knee Arthroplasty

NCT ID: NCT02349542

Last Updated: 2017-08-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2016-11-21

Brief Summary

The purpose of this study is to evaluate the serum levels (pharmacokinetics) of bupivacaine in a series of patients undergoing simultaneous bilateral total knee arthroplasty with the use of a standardized periarticular injection containing free bupivacaine and liposomal bupivacaine.

Detailed Description

Total knee arthroplasty (TKA) is a commonly performed and successful surgical procedure that has been shown to dramatically decrease pain and improve patient's function and quality of life. Certain patients may present with significant pain and limitations due to pain in both knees and based on age, health and degree of deformity may be candidates for bilateral simultaneous total knee arthroplasty. The safety and efficacy of simultaneous bilateral total knee arthroplasty has been well documented in the literature.

Inadequate postoperative pain control following TKA has been one of the greatest sources of patient dissatisfaction following total knee arthroplasty. Traditionally, it has been managed with parenteral and oral narcotics. Recently, a number of studies have demonstrated the efficacy of multimodal analgesia following a variety of surgical procedures. These multimodal regimens vary and consist of any number of medications including non-steroidal anti-inflammatories, anti-epileptics, and peripheral nerve blocks among others. These multimodal regimens have been associated with a reduction in the use of opioid analgesics, leading to fewer opioid-associated adverse events.

One of the newest modalities introduced on the market is liposomal bupivacaine (Exparel). Liposomal bupivacaine is a lipid encapsulated bupivacaine that allows for depo administration of the medication into the soft tissue during a surgical procedure. The lipids are engineered to slowly release over an approximately 72 hour time period, resulting in the slow release of free bupivacaine in to the soft tissue of the surgical site. This has the proposed advantage of a longer duration of analgesia compared to standard bupivacaine injections.

Liposomal bupivacaine is applied in a periarticular injection at the conclusion of TKAs to aid in post-operative pain control. Due to the lipid encapsulation of the bupivacaine, only 3% free bupivacaine is released into the tissue at initial infiltration, with the remainder released slowly over approximately a 72 hour time frame. To cover, this gap period, the liposomal bupivacaine is mixed with standard bupivacaine to allow for an immediate analgesic effect.

A potential risk, although low, is the concern for bupivacaine toxicity. Toxicity from bupivacaine is associated with central nervous system issues (seizures) and cardiac toxicity. Toxicity is dose dependent and recommended levels should not exceed 400mg/24 hr period. With the use of bupivacaine into each surgical site, there is a theoretical risk, if administered intra-vascularly, of bupivacaine toxicity. To date, no study has evaluated the safety of liposomal bupivacaine when used in simultaneous bilateral total knee arthroplasty. The use of liposomal bupivacaine is FDA approved for infiltration of one vial into one surgical site. Other specialties have evaluated the use of one vial of liposomal bupivacaine into two surgical sites (breast augmentation) at one surgery without any adverse events.

To date, approximately 8-10 patients at the investigator's institution have undergone simultaneous bilateral total knee arthroplasty with the use of liposomal bupivacaine without a known adverse event. A recent study published by Bramlett (2012) used 2 vials (532mg) in one knee to evaluate efficacy. There were no changes in patient's vitals signs or cardiac events in those patients receiving liposomal bupivacaine at the highest dose. In addition, a study by Bergese looked at doses of up to 600mg of liposomal bupivacaine in a Phase 2 safety study and found no adverse cardiac events. The purpose of this study is to evaluate the serum levels (pharmacokinetics) of bupivacaine in a series of patients undergoing simultaneous bilateral total knee arthroplasty with the use of a standardize periarticular injection containing free bupivacaine and liposomal bupivacaine.

Conditions

Arthroplasty, Replacement, Knee; Pain

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

Liposomal bupivacaine

Patients will receive liposomal bupivacaine following simultaneous bilateral total knee arthroplasty.

Group Type: EXPERIMENTAL

Liposomal bupivacaine

Intervention Type: DRUG

One (1) 20 mL vial of 266 mg liposomal bupivacaine (3% (\~8mg free bupivacaine)) will be injected into each surgical (knee) site following simultaneous bilateral total knee arthroplasty. In addition, 30 mL of 0.25% bupivacaine (75 mg free bupivacaine) will be injected into each surgical (knee) site for a total of 83 mg free bupivacaine injected into each surgical (knee) site.

Interventions

Liposomal bupivacaine

One (1) 20 mL vial of 266 mg liposomal bupivacaine (3% (\~8mg free bupivacaine)) will be injected into each surgical (knee) site following simultaneous bilateral total knee arthroplasty. In addition, 30 mL of 0.25% bupivacaine (75 mg free bupivacaine) will be injected into each surgical (knee) site for a total of 83 mg free bupivacaine injected into each surgical (knee) site.

Intervention Type: DRUG

Other Intervention Names

Exparel

Eligibility Criteria

Inclusion Criteria

• Patients deemed appropriate candidates for simultaneous bilateral total knee arthroplasty.
• Patients receiving general anesthesia
• Understands the local language and is willing and able to follow the requirements of the protocol
• Understands the informed consent and signs the institutional review board/ independent ethics committee (IRB/IEC) approved informed consent form

Exclusion Criteria

• Patients less than 18 years of age
• Allergy to bupivacaine
• Allergy to epinephrine
• Patients who are not medically cleared to undergo bilateral total knee replacement surgery, or
• Patient-reported liver impairment (per investigator discretion)
• Patient-reported renal impairment (per investigator discretion)
• Patients receiving spinal anesthesia
• Females who are pregnant or lactating

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

OrthoCarolina Research Institute, Inc.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susan M Odum, PhD

Role: STUDY_DIRECTOR

Senior Research Scientist

Bryan D Springer, MD

Role: PRINCIPAL_INVESTIGATOR

Physician

Locations

OrthoCarolina, PA

Charlotte, North Carolina, United States

Countries

United States

References

Bosco JA 3rd, Slover JD, Haas JP. Perioperative strategies for decreasing infection: a comprehensive evidence-based approach. J Bone Joint Surg Am. 2010 Jan;92(1):232-9. No abstract available.

Reference Type: BACKGROUND

PMID: 20048118 (View on PubMed)

Zeni JA Jr, Snyder-Mackler L. Clinical outcomes after simultaneous bilateral total knee arthroplasty: comparison to unilateral total knee arthroplasty and healthy controls. J Arthroplasty. 2010 Jun;25(4):541-6. doi: 10.1016/j.arth.2009.02.016. Epub 2009 Apr 7.

Reference Type: BACKGROUND

PMID: 19356894 (View on PubMed)

Taylor BC, Dimitris C, Mowbray JG, Gaines ST, Steensen RN. Perioperative safety of two-team simultaneous bilateral total knee arthroplasty in the obese patient. J Orthop Surg Res. 2010 Jun 17;5:38. doi: 10.1186/1749-799X-5-38.

Reference Type: BACKGROUND

PMID: 20565781 (View on PubMed)

Shin YH, Kim MH, Ko JS, Park JA. The safety of simultaneous bilateral versus unilateral total knee arthroplasty: the experience in a Korean hospital. Singapore Med J. 2010 Jan;51(1):44-9.

Reference Type: BACKGROUND

PMID: 20200775 (View on PubMed)

Kim SY, An YJ, Kim SH, Kim HK, Park JS, Shin YS. The effect of postoperative pain on postoperative blood loss after sequential bilateral total knee arthroplasty. Korean J Anesthesiol. 2011 Feb;60(2):98-102. doi: 10.4097/kjae.2011.60.2.98. Epub 2011 Feb 25.

Reference Type: BACKGROUND

PMID: 21390164 (View on PubMed)

Parvizi J, Miller AG, Gandhi K. Multimodal pain management after total joint arthroplasty. J Bone Joint Surg Am. 2011 Jun 1;93(11):1075-84. doi: 10.2106/JBJS.J.01095.

Reference Type: BACKGROUND

PMID: 21655901 (View on PubMed)

Goyal N, McKenzie J, Sharkey PF, Parvizi J, Hozack WJ, Austin MS. The 2012 Chitranjan Ranawat award: intraarticular analgesia after TKA reduces pain: a randomized, double-blinded, placebo-controlled, prospective study. Clin Orthop Relat Res. 2013 Jan;471(1):64-75. doi: 10.1007/s11999-012-2596-9.

Reference Type: BACKGROUND

PMID: 23011843 (View on PubMed)

Hutchinson RW, Chon EH, Gilder R, Moss J, Daniel P. A comparison of a fentanyl, morphine, and hydromorphone patient-controlled intravenous delivery for acute postoperative analgesia: a multicenter study of opioid-induced adverse reactions. Hospital Pharmacy 41(7): 659-663, 2006.

Reference Type: BACKGROUND

Jin F, Chung F. Multimodal analgesia for postoperative pain control. J Clin Anesth. 2001 Nov;13(7):524-39. doi: 10.1016/s0952-8180(01)00320-8.

Reference Type: BACKGROUND

PMID: 11704453 (View on PubMed)

Busch CA, Shore BJ, Bhandari R, Ganapathy S, MacDonald SJ, Bourne RB, Rorabeck CH, McCalden RW. Efficacy of periarticular multimodal drug injection in total knee arthroplasty. A randomized trial. J Bone Joint Surg Am. 2006 May;88(5):959-63. doi: 10.2106/JBJS.E.00344.

Reference Type: BACKGROUND

PMID: 16651569 (View on PubMed)

Horlocker TT, Hebl JR, Kinney MA, Cabanela ME. Opioid-free analgesia following total knee arthroplasty--a multimodal approach using continuous lumbar plexus (psoas compartment) block, acetaminophen, and ketorolac. Reg Anesth Pain Med. 2002 Jan-Feb;27(1):105-8. doi: 10.1053/rapm.2002.27177.

Reference Type: BACKGROUND

PMID: 11799514 (View on PubMed)

Lombardi AV Jr, Berend KR, Mallory TH, Dodds KL, Adams JB. Soft tissue and intra-articular injection of bupivacaine, epinephrine, and morphine has a beneficial effect after total knee arthroplasty. Clin Orthop Relat Res. 2004 Nov;(428):125-30. doi: 10.1097/01.blo.0000147701.24029.cc.

Reference Type: BACKGROUND

PMID: 15534532 (View on PubMed)

Bramlett K, Onel E, Viscusi ER, Jones K. A randomized, double-blind, dose-ranging study comparing wound infiltration of DepoFoam bupivacaine, an extended-release liposomal bupivacaine, to bupivacaine HCl for postsurgical analgesia in total knee arthroplasty. Knee. 2012 Oct;19(5):530-6. doi: 10.1016/j.knee.2011.12.004. Epub 2012 Jan 28.

Reference Type: BACKGROUND

PMID: 22285545 (View on PubMed)

Minkowitz HS, Onel E, Patronella CK, Smoot JD. A two-year observational study assessing the safety of DepoFoam bupivacaine after augmentation mammaplasty. Aesthet Surg J. 2012 Feb;32(2):186-93. doi: 10.1177/1090820X11434524. Epub 2012 Jan 11.

Reference Type: BACKGROUND

PMID: 22238339 (View on PubMed)

Other Identifiers

11-14-10B

Identifier Type: -

Identifier Source: org_study_id