Zynrelef Versus Adductor Canal Block

NCT07216586 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 20250529
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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

Outcome Measures

Primary Outcomes (1)

• 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)

  12, 16, 20, 24, 48, and 72 hours after surgery

Secondary Outcomes (3)

• Visual Analog Scale (VAS) pain scores

  4 hours after surgery and 6 weeks

• Hospital length of stay measured in hours

  7 days

• Knee range of motion

  Within 48 hours of surgery, 6 weeks follow up

Study Arms (2)

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.

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.

Procedure: Ultrasound-Guided Adductor Canal Block; Drug: Ropivacaine 0.5% Injectable Solution

Interventions

ZYNRELEF 400Mg-12Mg Extended-Release Solution DRUG

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.

Also known as: HTX-011

Zynrelef (HTX-011) with application procedure

Ultrasound-Guided Adductor Canal Block PROCEDURE

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.

Adductor canal block (ACB)

Ropivacaine 0.5% Injectable Solution DRUG

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.

Adductor canal block (ACB)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients \> 18 years of age
• Patients undergoing primary, unilateral total knee arthroplasty
• Ability to provide informed consent

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

University of Miami

Miami, Florida, 33125, United States

Location

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

bupivacaine-meloxicam drug combination; Ropivacaine

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Colin A. McNamara, MD,MBA

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natalia Cruz, MD

CONTACT

305-689-5195; nxc971@miami.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Orthopaedic Surgery

Study Record Dates

• First Submitted: October 10, 2025
• First Posted: October 14, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)