ZYNRELEF for Pain Management in Total Knee Arthroplasty

Study Overview
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Brief Summary
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The goal of this randomized controlled trial is to compare opioid medication consumption after surgery for patients who have a total knee replacement. The main questions it aims to answer are: How well does the study drug control pain in the days after surgery? Does the study drug reduce the amount of opioid analgesic consumed after surgery? Participants in the study group will undergo a total knee replacement as planned with their surgeon. In addition, be given the study drug, Zynrelef (combination of bupivacaine and meloxicam). Researchers will compare the above to a control group who will have a total knee replace only according to usual standards to see if there are any differences in the amount of a type of pain medication (opioid analgesic) consumed in the days following surgery.

Official Title
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A Randomized Controlled Trial of ZYNRELEF Versus Standard of Care for Pain Management Following Unilateral Total Knee Arthroplasty

Conditions
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Post Operative Pain, Osteoarthritis, Knee

Intervention / Treatment
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* Drug: Bupivacaine-Meloxicam 400 Mg-12 Mg/14 mL Injectable Solution, Extended Release


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients undergoing primary unilateral total knee arthroplasty [Current Procedural Terminology Code: 27447] Patients with a diagnosis of primary osteoarthritis [ICD-10 codes: M17.0, M17.10, M17.11, M17.12] Varus deformity less than 10 degrees Flexion contracture less than 10 degrees Age 35 - 70 years old BMI < 40 Patients who are discharged on the same day after the unilateral total knee arthroplasty procedure Exclusion Criteria: Inflammatory arthritis Post-traumatic arthritis Valgus deformity Severe varus (> 10 degrees) Severe flexion contracture (> 10 degrees) Overnight or longer hospital stay after surgery Prior surgery on affected knee other than knee arthroscopy for meniscal or cartilage debridement/repair Creatinine > 1.2 Chronic Kidney Disease (CKD) stage 3, 4, 5 or end stage renal disease Uncontrolled Diabetes mellitus (Glycated Hemoglobin > 8.0%) Current liver disease Personal history of depression or anxiety disorder Personal history of Deep Venous Thrombosis (DVT) or Pulmonary Embolism (PE) Narcotic or tramadol use within 2 weeks of the planned procedure Allergy to aspirin, NSAIDS, oxycodone, Tylenol, local anesthetics Walking aid for anything other than the operative joint Contraindication for use of the study drug (as specified by the manufacturer): Known hypersensitivity to local amide anesthetics, NSAIDs or study drug components History of asthma, urticaria or other allergic-type reactions to aspirin or other NSAIDs Patients taking the following medications: Amitriptyline Nortriptyline Gabapentin Pregabalin Duloxetine (SNRI) Des-Venlafaxine (SNRI) Cyclobenzaprine Baclofen Pregnant or lactating females Patients unable to provide informed consent Subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 70 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: Intervention<br>In addition to the standard-of-care arm description, single administration of Bupivacaine-Meloxicam 400 Mg-12 Mg/14 mL Injectable Solution, Extended Release in the surgical site before complete wound closure. | Drug: Bupivacaine-Meloxicam 400 Mg-12 Mg/14 mL Injectable Solution, Extended Release<br>* Instillation of the drug into the knee joint capsule and surrounding tissues after placing the knee prosthesis and before close of the surgical wound<br>* Other names: Zynrelef;|
| No Intervention: Standard-of-care<br>Usual standard of care procedure for knee replacement and pain management before, during and immediately following surgery. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total opioid analgesic consumption | Amount of opioid analgesic consumed in the time frame calculated as Morphine Milligram Equivalent (MME). | 5 days following surgical procedure | 
| Change in pain assessment scores | Pain assessment scores using the pain Numeric Rating Scale for pain (NRS). The NRS scale is measured on a scale of 0 - 10, where 0 is no pain and 10 is the most severe pain. | Baseline and every 24 hours for 120 hours following surgical procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of major complications | Number of procedure-related adverse events and medication-related adverse events. | 42 days following surgical procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Knee Arthroplasty, Postoperative pain management