ZYNRELEF for Pain Management in Total Knee Arthroplasty

Phase 4

Recruiting

• Conditions: Post Operative Pain; Osteoarthritis, Knee
• Interventions: Drug: Bupivacaine-Meloxicam 400 Mg-12 Mg/14 mL Injectable Solution, Extended Release

• Registration Number: NCT05644496
• Lead Sponsor: Baptist Health South Florida

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-11-11
• Study First Submitted QC: 2022-12-07
• Study First Posted: 2022-12-09
• Study Start: 2023-03-09
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-16
• Last Update Posted: 2025-04-18
• Primary Completion: 2027-10
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 242

Inclusion Criteria

1. Adult patients undergoing primary unilateral total knee arthroplasty [Current Procedural Terminology Code: 27447]
2. Patients with a diagnosis of primary osteoarthritis [ICD-10 codes: M17.0, M17.10, M17.11, M17.12]
3. Varus deformity less than 10 degrees
4. Flexion contracture less than 10 degrees
5. Age 35 - 70 years old
6. BMI < 40
7. Patients who are discharged on the same day after the unilateral total knee arthroplasty procedure

Exclusion Criteria

1. Inflammatory arthritis

2. Post-traumatic arthritis

3. Valgus deformity

4. Severe varus (> 10 degrees)

5. Severe flexion contracture (> 10 degrees)

6. Overnight or longer hospital stay after surgery

7. Prior surgery on affected knee other than knee arthroscopy for meniscal or cartilage debridement/repair

8. Creatinine > 1.2

9. Chronic Kidney Disease (CKD) stage 3, 4, 5 or end stage renal disease

10. Uncontrolled Diabetes mellitus (Glycated Hemoglobin > 8.0%)

11. Current liver disease

12. Personal history of depression or anxiety disorder

13. Personal history of Deep Venous Thrombosis (DVT) or Pulmonary Embolism (PE)

14. Narcotic or tramadol use within 2 weeks of the planned procedure

15. Allergy to aspirin, NSAIDS, oxycodone, Tylenol, local anesthetics

16. Walking aid for anything other than the operative joint

17. 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

18. Patients taking the following medications:

    • Amitriptyline
    • Nortriptyline
    • Gabapentin
    • Pregabalin
    • Duloxetine (SNRI)
    • Des-Venlafaxine (SNRI)
    • Cyclobenzaprine
    • Baclofen

19. Pregnant or lactating females

20. Patients unable to provide informed consent

21. Subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	Bupivacaine-Meloxicam 400 Mg-12 Mg/14 mL Injectable Solution, Extended Release	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.

Primary Outcome Measures

Name	Time	Method
Total opioid analgesic consumption	5 days following surgical procedure	Amount of opioid analgesic consumed in the time frame calculated as Morphine Milligram Equivalent (MME).
Change in pain assessment scores	Baseline and every 24 hours for 120 hours following surgical procedure	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.

Secondary Outcome Measures

Name	Time	Method
Incidence of major complications	42 days following surgical procedure	Number of procedure-related adverse events and medication-related adverse events.

Trial Locations

Locations (1)

Doctors Hospital; 🇺🇸 Miami, Florida, United States