Zynrelef vs Adductor Canal Block for Knee Arthritis

Overseen By Natalia Cruz, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Miami

Must not be taking: Opioids, Bupivacaine, NSAIDs

Disqualifiers: Pregnancy, Prisoners, Alcohol abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: 72 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods for managing pain after knee replacement surgery. One group receives Zynrelef, a pain-relief medication applied directly to the knee during surgery. The other group receives an adductor canal block, a type of nerve block that helps reduce pain. The researchers aim to determine which method reduces the need for pain medication in the first three days after surgery. Ideal participants are those undergoing their first knee replacement on one knee and who do not regularly use opioids. As a Phase 4 trial, this study involves treatments already FDA-approved and proven effective, aiming to understand how they can benefit more patients.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you cannot take long-acting opioids within 3 days, any opioids within 24 hours, or Bupivacaine HCL within 5 days before surgery.

What is the safety track record for ZYNRELEF and Ropivacaine?

Research has shown that Zynrelef (HTX-011) is safe to use. In studies involving over 1,600 patients undergoing various surgeries, Zynrelef was generally well-tolerated. These studies found that patients experienced good pain relief and required fewer strong painkillers, such as opioids.

The safety data from these studies revealed no unexpected side effects. Patients reported common surgery-related side effects like nausea and dizziness, but these were not specific to Zynrelef. Importantly, the FDA has approved Zynrelef for use in surgeries, supporting its safety for managing pain. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

ZYNRELEF is unique because it combines two active ingredients, bupivacaine and meloxicam, to provide pain relief directly at the surgical site. Most treatments for knee arthritis pain, like oral painkillers or nerve blocks, work by being absorbed into the bloodstream or targeting nerves indirectly. In contrast, ZYNRELEF is applied directly to the tissues around the knee joint during surgery, which can lead to more precise pain management. This targeted delivery could mean faster and potentially more effective pain relief right where it's needed most, exciting researchers about its potential benefits over traditional methods.

What evidence suggests that this trial's treatments could be effective for knee arthritis?

This trial will compare ZYNRELEF with an adductor canal block (ACB) for managing pain in knee arthritis surgery. Research has shown that ZYNRELEF reduces pain after surgery. Specifically, studies have found that ZYNRELEF provides better pain relief for up to 72 hours compared to bupivacaine, a common pain medication. Additionally, ZYNRELEF can reduce the need for opioids, with some patients not requiring opioids at all. This treatment combines bupivacaine and meloxicam to manage pain and swelling. Overall, ZYNRELEF shows promise for effectively managing post-surgical pain. ^{3 5 6 7 8}

Who Is on the Research Team?

Colin A. McNamara, MD,MBA

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for adults over 18 undergoing primary, unilateral total knee arthroplasty who can consent. It excludes pregnant women, prisoners, those with a history of drug or alcohol abuse, allergies to local anesthetics or NSAIDs, severe asthma reactions to aspirin/NSAIDs, and patients on certain pain medications.

Inclusion Criteria

I am over 18 years old.

I can understand and agree to the study's procedures and risks.

I am having a knee replacement surgery on one knee.

Exclusion Criteria

Pregnant women

Prisoners

Illicit drug use determined by social history

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either Zynrelef or adductor canal block during and after total knee arthroplasty

72 hours

In-hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain scores and knee range of motion

6 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ropivacaine
• ZYNRELEF

Trial Overview The study compares postoperative opioid use in two groups after knee surgery: one receiving Zynrelef (an extended-release solution) during surgery and the other getting an adductor canal block with Ropivacaine. The focus is on medication use within the first 72 hours post-surgery.

How Is the Trial Designed?

Group I: Zynrelef (HTX-011) with application procedure Experimental Treatment 1 Intervention

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.

Group II: Adductor canal block (ACB) Active Control 2 Interventions

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.

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40711999/

A Randomized Clinical Trial Showing Similar Efficacy in ... The primary outcome was the area under the curve (AUC) for NRS pain, adjusted for opioid consumption, over 72 hours. The minimal clinically ...

2. zynrelef.com zynrelef.com/efficacy-pain-reduction/

72 Hours of Postoperative Pain Relief ZYNRELEF patients experienced superior pain relief through 72 hours compared to patients receiving bupivacaine HCl solution.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0883540320305842

HTX-011 Reduced Pain and Opioid Use After Primary Total ... Needle-free application of HTX-011 400 mg bupivacaine/12 mg meloxicam provided superior pain reduction through 72 hours after total knee arthroplasty.

4. zynrelef.com zynrelef.com/

ZYNRELEF: Dual-Acting Local Anesthetic ZYNRELEF is indicated in adults for instillation to produce postsurgical analgesia for up to 72 hours after soft tissue and orthopedic procedures.

5. ir.herontx.com ir.herontx.com/news-releases/news-release-details/heron-therapeutics-announces-publication-showing-zynrelefr

News Release Details ZYNRELEF demonstrated superior, sustained postoperative pain relief for up to 72 hours and decreased the need for opioids, with more patients opioid-free ...

6. zynrelef.com zynrelef.com/safety/

Safety Profile of side effects and adverse reactions from Phase 2b TKA, EPOCH 1 Bunionectomy, EPOCH 2 Herniorrhaphy, and all associated follow-on clinical trials.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10289832/

HTX-011 in Combination with Multimodal Analgesic ... In a prior randomized controlled trial (RCT), HTX-011 reduced pain and opioid use through 72 hours after TKA compared with bupivacaine ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/211988Orig1s013.pdf

211988Orig1s013 | FDA The safety of ZYNRELEF has been evaluated in a total of 1627 patients undergoing various surgical procedures across 14 clinical studies ...