ZYNRELEF for Pain Management in Total Knee Arthroplasty

Osteoarthritis, Knee Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05644496
• Other study ID #: 1891382
• Status: Recruiting
• Phase: Phase 4
• Start date: March 9, 2023
• Est. completion date: April 2026

Study information

• Verified date: March 2024
• Source: Baptist Health South Florida
• Contact: Yvette Hernandez
• Phone: 786-308-2217
• Email: yvettesal[@]baptisthealth.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 242
• Est. completion date: April 2026
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Osteoarthritis, Knee
• Pain, Postoperative
• Post Operative Pain

Intervention

Drug:
• Bupivacaine-Meloxicam 400 Mg-12 Mg/14 mL Injectable Solution, Extended Release
Instillation of the drug into the knee joint capsule and surrounding tissues after placing the knee prosthesis and before close of the surgical wound

Locations

Country	Name	City	State
United States	Doctors Hospital	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Baptist Health South Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total opioid analgesic consumption	Amount of opioid analgesic consumed in the time frame calculated as Morphine Milligram Equivalent (MME).	5 days following surgical procedure
Primary	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	Incidence of major complications	Number of procedure-related adverse events and medication-related adverse events.	42 days following surgical procedure