Clinical trial NCT02349542: Liposomal Bupivacaine in Simultaneous Bilateral Total Knee Arthroplasty
Official title: The Safety of Liposomal Bupivacaine in Simultaneous Bilateral Total Knee Arthroplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Arthroplasty, Replacement, Knee
Pain
Keywords: Liposomal Bupivacaine
Simultaneous Bilateral Total Knee Arthroplasty
Safety
Lead sponsor: OrthoCarolina Research Institute, Inc.
Sponsor class: OTHER
First posted: 2015-01-29
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: HEALTH_SERVICES_RESEARCH

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.

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

Primary outcomes:
measure: Adverse Events
timeFrame: Up to 72 hours following injection
Secondary outcomes:
measure: Plasma Bupivacaine Levels
timeFrame: Up to 72 hours following injection
Other outcomes:
Locations:
city: Charlotte
country: United States
facility: OrthoCarolina, PA
state: North Carolina
Study officials:
affiliation: Senior Research Scientist
name: Susan M Odum, PhD
role: STUDY_DIRECTOR
affiliation: Physician
name: Bryan D Springer, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
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