Post-Operative Pain Relief: Zynrelef or Periarticular Injections in RATKA

Postoperative Pain Outcomes After Use of Bupivacaine-Meloxicam Extended-Release Solution in Robot Assisted Total Knee Arthroplasty: A Prospective Study

Prospective Cohort of patients who are scheduled for a Robot Assisted Total Knee Arthroplasty (RATKA). A prospective survey of patient reported outcome measures (Numeric Rating Scale) will be obtained postoperatively of 72 hours, as well as at the postoperative opioid consumption after 72 hours.

Study Overview

• Status: Not yet recruiting
• Conditions: Knee Arthroplasty, Total; Osteoarthritis (OA); Osteoarthritis (OA) of the Knee; Periarticular Block; Pain After Surgery
• Intervention / Treatment: Combination product: bupivacaine-meloxicam (extended release); Drug: Bupivacaine; Drug: Ketorolac; Drug: Lidocaine (drug)

Detailed Description

Opioid use is a well-discussed issue in the United States among orthopedic surgeons, as while these drugs are helpful and necessary, they pose the risk of addiction and ultimately should be used as sparingly as possible. By taking a multimodal approach to pain management, this can be successfully achieved. Periarticular injections are currently used to achieve this goal, and 2021 a bupivacaine-meloxicam extended-release periarticular injection (Zynrelef) was introduced and is regularly implemented into RATKAs. Randomized clinical trials found that Zynrelef's use in traditional total knee arthroplasties (TKA) was just as effective as standard periarticular injections in reducing opioid use and pain, but whether Zynrelef works just as well if not better in RATKA is not yet established.

Objectives: (primary and important secondary objectives)

To evaluate the improvement in pain and use of opioids of a patient who received Zynrelef after undergoing RATKA compared to the traditional periarticular injections commonly used. The secondary objective will be documentation of the patient's use of other oral (over-the-counter) OTC pain relievers, such as acetaminophen or NSAIDs (non-steroidal anti inflammatory drugs).

Study Design:

Prospective Cohort Study (double arm)

Setting/Participants:

Patients who have undergone a standard of care RATKA at any Allegheny Health Network facility who consent to filling out a survey addressing their reported outcomes.

Study Interventions and Measures:

Patients will be evaluated with the Numeric Rating Scale (NRS) on postoperative days 1-3. Patients will be given paper forms which will be collected by the physicians at their next postoperative visit. A retrospective review of Epic Electronic Medical Records (EMR) will also be conducted to describe basic demographic characteristics.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Obinna Ajah, MD; Phone Number: 877-660-6777; Email: obinna.ajah@ahn.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Males or females aged 18-89 years

Diagnosed with knee osteoarthritis requiring surgical intervention

Indicated for unilateral RATKA

Exclusion Criteria:

Pediatric, pregnant, or incarcerated patients

BMI of more than 45 kg/m2

Prolonged opioid use history of >5 mg/day for >1 month

History of contralateral TKA <2 years prior to the index TKA

Type 1 Hypersensitivity to NSAIDs or local anesthetics

Diagnosis of severe renal disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zynrelef; Periarticular injection of bupivacaine-meloxicam extended release	Combination product: bupivacaine-meloxicam (extended release); These surgeons will be using Zynrelef (bupivacaine-meloxicam extended release) as a form of periarticular analgesia.
Active Comparator: Control; Periarticular injection of bupivacaine, ketorolac, and lidocaine	Drug: Bupivacaine; These surgeons will be using the control injection (bupivacaine + ketorolac + lidocaine) as a form of periarticular analgesia.; Drug: Ketorolac; These surgeons will be using the control injection (bupivacaine + ketorolac + lidocaine) as a form of periarticular analgesia.; Drug: Lidocaine (drug); These surgeons will be using the control injection (bupivacaine + ketorolac + lidocaine) as a form of periarticular analgesia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of opioid medications used (measured in morphine milligrams equivalents)	Self-report of opioid medications	From completion of surgery to 3 days post-op
Patient reported outcome measure (Numeric Rating Scale)	Self-report of pain using numeric scale. Title: Numeric Rating Scale; Ranges from 0 to 10, where 10 is maximal pain and 0 is no pain at all.	From completion of surgery to 3 days post-op

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complications and Adverse Events	Report of adverse events	From completion of surgery to 3 days post-op
Amount of oral Over-the-counter (OTC) pain reliever medications used	Self-report of Over-the-counter (OTC) pain relievers	From completion of surgery to 3 days post-operation

Collaborators and Investigators

• Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
• Investigators: Principal Investigator: Andrew Waligora, MD, Allegheny Health Network

Publications and helpful links

General Publications

• Joo PY, Chen AF, Richards J, Law TY, Taylor K, Marchand K, Clark G, Collopy D, Marchand RC, Roche M, Mont MA, Malkani AL. Clinical results and patient-reported outcomes following robotic-assisted primary total knee arthroplasty : a multicentre study. Bone Jt Open. 2022 Aug;3(8):589-595. doi: 10.1302/2633-1462.37.BJO-2022-0076.R1.
• Salmons, Harold I. MD, MS1; Amundson, Adam W. MD2; Duncan, Christopher M. MD2; Larson, Dirk R. MS3; Mallinger, Benjamin D. BS1; Couch, Cory G. MD1; Pagnano, Mark W. MD1; Trousdale, Robert T. MD1; Abdel, Matthew P. MD1,a. Bupivacaine-Meloxicam Extended-Release Solution Compared with a Standard Periarticular Injection in Primary Total Knee Arthroplasty: A Randomized Clinical Trial Showing Similar Efficacy in Postoperative Analgesia. The Journal of Bone and Joint Surgery 107(17):p 1918-1925, September 3, 2025. | DOI: 10.2106/JBJS.25.00086
• Blair HA. Bupivacaine/Meloxicam Prolonged Release: A Review in Postoperative Pain. Drugs. 2021 Jul;81(10):1203-1211. doi: 10.1007/s40265-021-01551-9.
• Dydyk AM, Jain NK, Gupta M. Opioid Use Disorder: Evaluation and Management. [Updated 2024 Jan 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.
• Cui A, Li H, Wang D, Zhong J, Chen Y, Lu H. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine. 2020 Nov 26;29-30:100587. doi: 10.1016/j.eclinm.2020.100587.

Study record dates

Study Major Dates

• Study Start (Estimated): January 31, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): February 28, 2028

Study Registration Dates

• First Submitted: February 18, 2026
• First Submitted That Met QC Criteria: February 18, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Zynrelef
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Indomethacin; Indoles; Bupivacaine; Ketorolac; Lidocaine; Pharmaceutical Preparations
• Other Study ID Numbers: 2025-344

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No