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

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

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.

Study Overview

• Status: Completed
• Conditions: Total Knee Arthroplasty
• Intervention / Treatment: Drug: HTX-011; Drug: ropivacaine , epinephrine , ketorolac diluted in sodium chloride

• Study Type: Interventional
• Enrollment (Actual): 209
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HTX-011 Treatment Group; Subjects undergoing a total knee arthroplasty will receive HTX-011 (Zynrelef) for perioperative analgesia	Drug: HTX-011; Single dose administration periarticular 400mg bupivacaine and 12mg meloxicam extended release solution; Other Names: Zynrelef
Active Comparator: Standard Block Control Group; Subjects undergoing a total knee arthroplasty will receive standard of care arthroplasty block for perioperative analgesia	Drug: ropivacaine , epinephrine , ketorolac diluted in sodium chloride; 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; Other Names: Mayo Clinic standard arthroplasty block

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Control at 72 Hours Postoperatively	Area Under the Curve (AUC) of the graph for mean Numerical Rated Score (NRS) for pain (0-10) over time (0-72 hours) / NRS AUC 0-72. Pain scores were collected by patient self-report 15 times over the 72 hours after surgery, and averaged amongst the patients for each study arm. Lower values represent better pain control based on lower mean 0-10 pain scores over the 72 hour period after surgery. The minimum value is 0, meaning patients reported 0 pain on a 0-10 scale at all 15 time points within 72 hours. The maximum value would be 720, meaning patients reported a 10 for pain on a 0-10 scale at all 15 time points within 72 hours.	72-hours postoperatively after total knee arthroplasty

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Control at 48 Hours Postoperatively	Area Under the Curve (AUC) of the graph for mean Numerical Rated Score (NRS) for pain (0-10) over time (0-48 hours) / NRS AUC 0-48. Pain scores were collected by patient self-report 11 times over the 48 hours after surgery, and averaged amongst the patients for each study arm. Lower values represent better pain control based on lower mean 0-10 pain scores over the 48 hour period after surgery. The minimum value is 0, meaning patients reported 0 pain on a 0-10 scale at all 11 time points within 48 hours. The maximum value would be 480, meaning patients reported a 10 for pain on a 0-10 scale at all 11 time points within 48 hours	48-hours postoperative total knee arthroplasty
Opioid Consumption 72 Hours Postoperatively	Total postoperative opioid consumption standardized into morphine milligram equivalents (MMEs)	72-hours postoperative total knee arthroplasty
Opioid Consumption 48 Hours Postoperatively	Total postoperative opioid consumption standardized into morphine milligram equivalents (MMEs)	48 hours postoperative total knee arthroplasty

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Matthew P Abdel, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2022
• Primary Completion (Actual): April 18, 2024
• Study Completion (Actual): April 18, 2024

Study Registration Dates

• First Submitted: December 27, 2021
• First Submitted That Met QC Criteria: January 11, 2022
• First Posted (Actual): January 12, 2022

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 11, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antirheumatic Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Respiratory System Agents; Anti-Asthmatic Agents; Bronchodilator Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Ropivacaine; Ketorolac; Epinephrine
• Other Study ID Numbers: 21-010044

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No