Knee OsteoarthritisPhase 4NCT07216586
Zynrelef Versus Adductor Canal Block
A Phase 4 study testing ZYNRELEF 400Mg-12Mg Extended-Release Solution, Ultrasound-Guided Adductor Canal Block and Ropivacaine 0.5% Injectable Solution in people with Knee Osteoarthritis and Arthritis Knee, run by University of Miami at 1 site in United States.
Trial summary
To compare postoperative MME consumption 72 hours after TKA in patients receiving intraoperative periarticular HTX-011 (Zynrelef) instillation versus adductor canal block. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Knee Osteoarthritis, Arthritis Knee
- What is being tested?
- ZYNRELEF 400Mg-12Mg Extended-Release Solution, Ultrasound-Guided Adductor Canal Block and Ropivacaine 0.5% Injectable Solution
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2027to Jan 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients > 18 years of age
- Patients undergoing primary, unilateral total knee arthroplasty
- Ability to provide informed consent
Who cannot join
- Individuals under the age of 18
- Pregnant women
- Prisoners
- Adults unable to consent
- American Society of Anesthesiologists Physical Status score greater than 3
- Patients taking any of the following medications before surgery:
Show all 14Show fewer
- Long-acting opioids within 3 days
- Any opioids taken within 24 hours
- Bupivacaine HCL within 5 days
- Chronic opioid use or patients with known or suspected daily use of opioids for seven or more consecutive days within 6 months before their scheduled surgery
- Illicit drug use determined by social history
- Alcohol abuse determined by a CAGE Substance Abuse Screening Tool Score of at least two or greater
- Patients with a known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to any local anesthetic agent of the amide-type, NSAIDs, or to any of the other components of ZYNRELEF
- Patients with a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
University of Miami
Miami, Florida, 33125
Natalia Cruz, MD, 305-689-5195, nxc971@miami.edu
Colin A. McNamara, MD,MBA
About this study
Official title: Comparing Opioid Consumption Following Total Knee Arthroplasty With The Perioperative Administration of Zynrelef Versus Adductor Canal Block
To compare postoperative MME consumption 72 hours after TKA in patients receiving intraoperative periarticular HTX-011 (Zynrelef) instillation versus adductor canal block.
- Conditions
- Knee Osteoarthritis, Arthritis Knee
- Being tested
- ZYNRELEF 400Mg-12Mg Extended-Release Solution, Ultrasound-Guided Adductor Canal Block, Ropivacaine 0.5% Injectable Solution
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZYNRELEF 400Mg-12Mg Extended-Release SolutionDrug
Also called HTX-011
A single 14 mL dose of HTX-011 containing 400 mg bupivacaine and 12 mg meloxicam will be applied intraoperatively to the surgical site. This FDA-approved formulation is designed to provide sustained analgesia for up to 72 hours following total knee arthroplasty.
Ultrasound-Guided Adductor Canal BlockProcedure or surgery
A board-certified anesthesiologist or regional anesthesia-trained provider will perform an ultrasound-guided adductor canal block under sterile conditions while the patient remains under spinal anesthesia. A high-frequency linear ultrasound probe will be used to visualize the adductor canal and saphenous nerve.
Ropivacaine 0.5% Injectable SolutionDrug
A single injection of 30 mL of 0.5% ropivacaine will be administered into the adductor canal to provide postoperative analgesia. This dose is standard for adductor canal blocks and is intended to minimize motor blockade while providing effective pain control.
| Study group | Role | What they receive |
|---|---|---|
| Zynrelef (HTX-011) with application procedure | Experimental | Participants in this group will receive intraoperative analgesia via application of ZYNRELEF (HTX-011) directly into the periarticular tissues at the surgical site following prosthesis implantation and prior to capsule closure. The medication will be applied by the surgeon using sterile technique per manufacturer instructions, targeting the posterior capsule, medial and lateral gutters, and surrounding soft tissues. Receives: Drug: ZYNRELEF 400Mg-12Mg Extended-Release Solution |
| Adductor canal block (ACB) | Active comparator | Participants in this group will receive a postoperative ultrasound-guided adductor canal block performed by a board-certified anesthesiologist or regional anesthesia-trained provider. The procedure will be conducted under sterile conditions while the patient remains under spinal anesthesia. Receives: Procedure: Ultrasound-Guided Adductor Canal Block; Drug: Ropivacaine 0.5% Injectable Solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Milligram Morphine Equivalents (MME)
Mean cumulative milligram morphine equivalents (MME) administered at 4, 8, 12, 16, 20, 24, 48, and 72 hours following total knee arthroplasty (TKA). Values will be compared between patients receiving Zynrelef and those receiving adductor canal block (ACB)
Measured: 12, 16, 20, 24, 48, and 72 hours after surgery
Secondary outcomes (3)
Visual Analog Scale (VAS) pain scores
Pain scores assessed 4 hours after surgery and at 6 weeks follow up using the Visual Analog Scale (VAS) for pain assessment consists of a line drawn in the form of a ruler, and numbers from 0 to 10 (with 0 as "no pain" and 10 as "unbearable pain"
Measured: 4 hours after surgery and 6 weeks
Hospital length of stay measured in hours
Average hospital length of stay measured in hours
Measured: 7 days
Knee range of motion
Knee range of motion will be measured in degrees using a standardized goniometer or equivalent clinical tool. Assessments will be conducted postoperatively (within 48 hours of surgery) and at 6-week follow-up. Higher degrees indicate improved joint mobility.
Measured: Within 48 hours of surgery, 6 weeks follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2025
- Study startJan 2027 (estimated)
- Primary completionJan 2028 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Knee OsteoarthritisStudies 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
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Colin A. McNamara, University of Miami
- Investigators
- Colin A. McNamara, MD,MBA, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07216586
- Sponsor's protocol ID
- 20250529
- Status last verified
- Feb 2026
- First submitted
- 10 Oct 2025
- Last updated
- 12 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparing Opioid Consumption Following Total Knee Arthroplasty With The Perioperative Administration of Zynrelef Versus Adductor Canal Block
- ClinicalTrials.gov ID
- NCT07216586
- Acronym / sponsor ID
- 20250529
- Conditions
- Knee Osteoarthritis, Arthritis Knee
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Study start
- Jan 2027 (estimated)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 14 Oct 2025 (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.
To compare postoperative MME consumption 72 hours after TKA in patients receiving intraoperative periarticular HTX-011 (Zynrelef) instillation versus adductor canal block.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zynrelef (HTX-011) with application procedure | Experimental | Drug: ZYNRELEF 400Mg-12Mg Extended-Release SolutionParticipants in this group will receive intraoperative analgesia via application of ZYNRELEF (HTX-011) directly into the periarticular tissues at the surgical site following prosthesis implantation and prior to capsule closure. The medication will be applied by the surgeon using sterile technique per manufacturer instructions, targeting the posterior capsule, medial and lateral gutters, and surrounding soft tissues. |
| Adductor canal block (ACB) | Active comparator | Procedure: Ultrasound-Guided Adductor Canal Block, Drug: Ropivacaine 0.5% Injectable SolutionParticipants in this group will receive a postoperative ultrasound-guided adductor canal block performed by a board-certified anesthesiologist or regional anesthesia-trained provider. The procedure will be conducted under sterile conditions while the patient remains under spinal anesthesia. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients > 18 years of age
- Patients undergoing primary, unilateral total knee arthroplasty
- Ability to provide informed consent
Key exclusion criteria (14 listed)
- Individuals under the age of 18
- Pregnant women
- Prisoners
- Adults unable to consent
- American Society of Anesthesiologists Physical Status score greater than 3
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 |
|---|---|---|
| ZYNRELEF 400Mg-12Mg Extended-Release SolutionAlso: HTX-011A single 14 mL dose of HTX-011 containing 400 mg bupivacaine and 12 mg meloxicam will be applied intraoperatively to the surgical site. This FDA-approved formulation is designed to provide sustained analgesia for up to 72 hours following total knee arthroplasty. | Drug | Zynrelef (HTX-011) with application procedure |
| Ultrasound-Guided Adductor Canal BlockA board-certified anesthesiologist or regional anesthesia-trained provider will perform an ultrasound-guided adductor canal block under sterile conditions while the patient remains under spinal anesthesia. A high-frequency linear ultrasound probe will be used to visualize the adductor canal and saphenous nerve. | Procedure or surgery | Adductor canal block (ACB) |
| Ropivacaine 0.5% Injectable SolutionA single injection of 30 mL of 0.5% ropivacaine will be administered into the adductor canal to provide postoperative analgesia. This dose is standard for adductor canal blocks and is intended to minimize motor blockade while providing effective pain control. | Drug | Adductor canal block (ACB) |
Primary outcome
Mean Milligram Morphine Equivalents (MME)
Time frame: 12, 16, 20, 24, 48, and 72 hours after surgery
Mean cumulative milligram morphine equivalents (MME) administered at 4, 8, 12, 16, 20, 24, 48, and 72 hours following total knee arthroplasty (TKA). Values will be compared between patients receiving Zynrelef and those receiving adductor canal block (ACB)
3 secondary outcomes
Visual Analog Scale (VAS) pain scores
Time frame: 4 hours after surgery and 6 weeks
Hospital length of stay measured in hours
Time frame: 7 days
Knee range of motion
Time frame: Within 48 hours of surgery, 6 weeks follow up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 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.
Colin A. McNamara, MD,MBA principal investigator
University of Miami
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 ZYNRELEF 400Mg-12Mg Extended-Release Solution, Ultrasound-Guided Adductor Canal Block and Ropivacaine 0.5% Injectable Solution in people with Knee Osteoarthritis and Arthritis Knee, run by University of Miami 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 3 inclusion and 14 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: opening soon, as of the sponsor's last update on 12 Jun 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Natalia Cruz, MD (305-689-5195, nxc971@miami.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Milligram Morphine Equivalents (MME) (time frame: 12, 16, 20, 24, 48, and 72 hours after surgery). 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 12 Jun 2026.