Post Operative PainPhase 4NCT05644496
ZYNRELEF for Pain Management in Total Knee Arthroplasty
A Phase 4 study testing Bupivacaine-Meloxicam 400 Mg-12 Mg/14 mL Injectable Solution, Extended Release in people with Post Operative Pain and Osteoarthritis, Knee, run by Baptist Health South Florida at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 35 to 70 years
- Conditions the study is for
- Post Operative Pain, Osteoarthritis, Knee
- What is being tested?
- Bupivacaine-Meloxicam 400 Mg-12 Mg/14 mL Injectable Solution, Extended Release
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Mar 2023to 19 Dec 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients undergoing primary unilateral total knee arthroplasty [Current Procedural Terminology Code: 27447]
- Patients with a diagnosis of primary osteoarthritis [ICD-10 codes: M17.0, M17.10, M17.11, M17.12]
- Varus deformity less than 10 degrees
- Flexion contracture less than 10 degrees
- Age 35 - 70 years old
- BMI < 40
- Patients who are discharged on the same day after the unilateral total knee arthroplasty procedure
Who cannot join
- Inflammatory arthritis
- Post-traumatic arthritis
- Valgus deformity
- Severe varus (> 10 degrees)
- Severe flexion contracture (> 10 degrees)
- Overnight or longer hospital stay after surgery
Show all 31Show fewer
- Prior surgery on affected knee other than knee arthroscopy for meniscal or cartilage debridement/repair
- Creatinine > 1.2
- Chronic Kidney Disease (CKD) stage 3, 4, 5 or end stage renal disease
- Uncontrolled Diabetes mellitus (Glycated Hemoglobin > 8.0%)
- Current liver disease
- Personal history of depression or anxiety disorder
- Personal history of Deep Venous Thrombosis (DVT) or Pulmonary Embolism (PE)
- Narcotic or tramadol use within 2 weeks of the planned procedure
- Allergy to aspirin, NSAIDS, oxycodone, Tylenol, local anesthetics
- Walking aid for anything other than the operative joint
- 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
- Patients taking the following medications:
- Amitriptyline
- Nortriptyline
- Gabapentin
- Pregabalin
- Duloxetine (SNRI)
- Des-Venlafaxine (SNRI)
- Cyclobenzaprine
- Baclofen
- Pregnant or lactating females
- Patients unable to provide informed consent
- Subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Controlled Trial of ZYNRELEF Versus Standard of Care for Pain Management Following Unilateral Total Knee Arthroplasty
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:
Read more
- 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.
- Conditions
- Post Operative Pain, Osteoarthritis, Knee
- Being tested
- Bupivacaine-Meloxicam 400 Mg-12 Mg/14 mL Injectable Solution, Extended Release
- Keywords
- Knee Arthroplasty, Postoperative pain management
- Medical subject headings
- Pain, Postoperative, Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bupivacaine-Meloxicam 400 Mg-12 Mg/14 mL Injectable Solution, Extended ReleaseDrug
Also called Zynrelef
Instillation of the drug into the knee joint capsule and surrounding tissues after placing the knee prosthesis and before close of the surgical wound
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | 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. Receives: Drug: Bupivacaine-Meloxicam 400 Mg-12 Mg/14 mL Injectable Solution, Extended Release |
| Standard-of-care | No intervention | Usual standard of care procedure for knee replacement and pain management before, during and immediately following surgery. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total opioid analgesic consumption
Amount of opioid analgesic consumed in the time frame calculated as Morphine Milligram Equivalent (MME).
Measured: 5 days following surgical procedure
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.
Measured: Baseline and every 24 hours for 120 hours following surgical procedure
Secondary outcomes (1)
Incidence of major complications
Number of procedure-related adverse events and medication-related adverse events.
Measured: 42 days following surgical procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2022
- Study start9 Mar 2023
- Primary completion19 Dec 2025
- Study completion19 Dec 2025
Why it stopped: Study discontinued due to feasibility challenges related to participant recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post Operative PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baptist Health South Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Juan C Suarez, MD, Principal investigator, Baptist Health South Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05644496
- Sponsor's protocol ID
- 1891382
- Status last verified
- May 2026
- First submitted
- 11 Nov 2022
- Last updated
- 28 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of ZYNRELEF Versus Standard of Care for Pain Management Following Unilateral Total Knee Arthroplasty
- ClinicalTrials.gov ID
- NCT05644496
- Acronym / sponsor ID
- 1891382
- Conditions
- Post Operative Pain, Osteoarthritis, Knee
- Keywords
- Knee Arthroplasty, Postoperative pain management
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study discontinued due to feasibility challenges related to participant recruitment
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Baptist Health South FloridaUniversity, hospital or other
- Study start
- 9 Mar 2023 (actual)
- Primary completion
- 19 Dec 2025 (actual)
- Study completion
- 19 Dec 2025 (actual)
- First posted
- 9 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: Bupivacaine-Meloxicam 400 Mg-12 Mg/14 mL Injectable Solution, Extended ReleaseIn 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. |
| Standard-of-care | No intervention | –Usual standard of care procedure for knee replacement and pain management before, during and immediately following surgery. |
Who may qualify
- Ages
- 35 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adult patients undergoing primary unilateral total knee arthroplasty [Current Procedural Terminology Code: 27447]
- Patients with a diagnosis of primary osteoarthritis [ICD-10 codes: M17.0, M17.10, M17.11, M17.12]
- Varus deformity less than 10 degrees
- Flexion contracture less than 10 degrees
- Age 35 - 70 years old
Key exclusion criteria (31 listed)
- Inflammatory arthritis
- Post-traumatic arthritis
- Valgus deformity
- Severe varus (> 10 degrees)
- Severe flexion contracture (> 10 degrees)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bupivacaine-Meloxicam 400 Mg-12 Mg/14 mL Injectable Solution, Extended ReleaseAlso: ZynrelefInstillation of the drug into the knee joint capsule and surrounding tissues after placing the knee prosthesis and before close of the surgical wound | Drug | Intervention |
Primary outcome
Total opioid analgesic consumption
Time frame: 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
Time frame: 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.
1 secondary outcome
Incidence of major complications
Time frame: 42 days following surgical procedure
Results and safety
The study was stopped early (reason given: Study discontinued due to feasibility challenges related to participant recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juan C Suarez, MD principal investigator
Baptist Health South Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bupivacaine-Meloxicam 400 Mg-12 Mg/14 mL Injectable Solution, Extended Release in people with Post Operative Pain and Osteoarthritis, Knee, run by Baptist Health South Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study discontinued due to feasibility challenges related to participant recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total opioid analgesic consumption (time frame: 5 days following surgical procedure). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2026.