Using ZYNRELEF to manage pain after knee replacement surgery

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

Phase 4 Interventional Baptist Health South Florida · NCT05644496

This study is testing if ZYNRELEF can help manage pain after knee replacement surgery better than standard care and reduce the need for opioids.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment242 (estimated)
Ages35 Years to 70 Years
SexAll
SponsorBaptist Health South Florida Academic / other
Locations1 site (Miami, Florida)
Trial IDNCT05644496 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of ZYNRELEF, a combination of bupivacaine and meloxicam, in managing postoperative pain for patients undergoing total knee arthroplasty. Participants will be randomly assigned to receive either the study drug or standard care, allowing researchers to compare opioid consumption in the days following surgery. The study focuses on understanding how well ZYNRELEF controls pain and whether it can reduce the need for opioid analgesics post-surgery.

Who should consider this trial

Good fit: Ideal candidates are adults aged 35 to 70 with primary osteoarthritis undergoing unilateral total knee arthroplasty.

Not a fit: Patients with inflammatory arthritis, severe deformities, or those requiring longer hospital stays may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved pain management strategies that reduce reliance on opioids after knee surgery.

How similar studies have performed: Other studies have shown promise in using local anesthetics and anti-inflammatory medications for postoperative pain management, suggesting this approach may be effective.

Eligibility criteria

Show full inclusion / exclusion criteria
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

Where this trial is running

Miami, Florida

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Post Operative PainOsteoarthritis, KneeKnee ArthroplastyPostoperative pain management
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.