Periarticular Bupivacaine + Meloxicam ER Solution Versus Standard Practice During Total Knee Arthroplasty

Study Overview
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Brief Summary
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The purpose of this study is to compare an FDA-approved medication for post-operative pain control (HTX-011) to the standard of care institutional practice for periarticular analgesia after primary total knee arthroplasty (weight based dosing of Ropivacaine, epinephrine and ketorolac diluted with saline). We are doing this research study to find out if this new medication provides superior pain control within 72 hours following surgery.

Official Title
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Periarticular Bupivacaine + Meloxicam ER Solution Versus Standard Practice During Total Knee Arthroplasty: A Single Institution, Single-blinded, Randomized Clinical Trial

Conditions
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Total Knee Arthroplasty

Intervention / Treatment
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* Drug: HTX-011
* Drug: ropivacaine , epinephrine , ketorolac diluted in sodium chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ASA classification I to III, older than or equal to 18 years old. Presenting for primary total knee replacement for degenerative joint disease. Patient capable of providing their own informed consent. Exclusion Criteria: Vulnerable study populations including prisoners. Patients with a contralateral total knee arthroplasty < 2 years prior to the index procedure. Compromised health barring them from proceeding with surgery including acute or chronic kidney injury identified pre-operative. Patients unable to provide their own informed consent. Pregnancy. Patients with documented chronic pain syndromes. Patients with a history of prolonged daily opioids (more than 1 month) with an oral morphine equivalent of greater than 5mg/day. BMI > 45 kg/m^2. Allergies to any component of the study medications, including specific history of type 1 hypersensitivities to any NSAID. Patients with impaired cognitive function. Major systemic illnesses such as severe renal (estimated glomerular filtration rate less than 50ml/min), coronary artery disease requiring a bypass graft (CABG), other cardiac problems including congestive heart failure (CHF New York Heart Association class III to IV), or severe hepatic disorders defined as current or past diagnosis of acute/subacute liver necrosis, acute hepatic failure, chronic liver disease, liver abscess, hepatic coma, hepatorenal syndrome and other disorders of the liver.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HTX-011 Treatment Group<br>Subjects undergoing a total knee arthroplasty will receive HTX-011 (Zynrelef) for perioperative analgesia | Drug: HTX-011<br>* Single dose administration periarticular 400mg bupivacaine and 12mg meloxicam extended release solution<br>* Other names: Zynrelef;|
| Active Comparator: Standard Block Control Group<br>Subjects undergoing a total knee arthroplasty will receive standard of care arthroplasty block for perioperative analgesia | Drug: ropivacaine , epinephrine , ketorolac diluted in sodium chloride<br>* Single dose administration in 100cc of standard formulation, there is 225mg of ropivacaine 5mg/mL, 0.6mg epinephrine 1mg/mL, 30mg ketorolac 30mg/mL diluted in sodium chloride<br>* Other names: Mayo Clinic standard arthroplasty block;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain control at 72 hours | Mean patient reported (0-10) numeric rating scale (NRS) pain scores at 72 hours postoperative | 72-hours postoperative total knee arthroplasty | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain control at 48 hours | Mean patient reported (0-10) numeric rating scale (NRS) pain scores at 48 hours postoperative | 48-hours postoperative total knee arthroplasty | 
| Pain control at 24 hours | Mean patient reported (0-10) numeric rating scale (NRS) pain scores at 24 hours postoperative | 24-hours postoperative total knee arthroplasty | 
| Opioid consumption | Total postoperative opioid consumption standardized into morphine milligram equivalents (MMEs) | 72-hours postoperative total knee arthroplasty | 
| Hospital length of stay | Total number of days admitted to the hospital | approximately 3 days | 
| Distance walked at time of discharge with PT | Distance walked by the participate with physical therapist (PT) at the time of discharge measured in meters | approximately 3 days |