Novel Extended-Release Bupivacaine Polymer for Sustained Pain Relief Following Total Knee Arthroplasty

Summary

Participants are being invited to take part in a research study about pain control after total knee replacement surgery (also called total knee arthroplasty or TKA). The goal of this study is to see if a new long-acting medication, called Zynrelef, can control pain after surgery as well as or better than two other common pain treatments - a nerve block or a standard injection into the knee during surgery.

Knee replacement is done to reduce pain and improve movement in people with severe knee arthritis. While the surgery can be very successful, pain during the first few days after surgery can make recovery harder. Many patients need strong opioid pain medicines, but these medicines can have side effects and may lead to dependence. The investigators want to find ways to control pain that reduce or even remove the need for opioids.

If participants join this study, they will be randomly placed (like flipping a coin) into one of three groups:

Standard injection (PAI) - a mix of medicines injected into the knee during surgery.

Zynrelef - a new long-acting medicine put directly into the knee during surgery, along with a smaller dose of the standard injection.

Nerve block (ACB) - medicine given near a nerve in the leg before surgery to block pain.

All participants will get the same medicines before and after surgery, follow the same physical therapy program, and have the same follow-up visits. Participants will be asked to record their pain scores and the pain medicines they take for several weeks after surgery.

The risks of joining are small and similar to those of routine care. All three pain control methods are already used in regular knee replacement surgery. Possible side effects may include temporary numbness, weakness, or soreness from the injections, and the usual surgical risks such as infection.

Participants may benefit from better pain control, less need for opioids, and a smoother recovery. The results from this study may also help future patients have safer and more comfortable knee replacements.

Taking part is voluntary. Participants can leave the study at any time without affecting their medical care.

Conditions

• Osteoarthritis (OA) of the Knee

Interventions

DRUG

Periarticular Injection

Study group I (standard PAI) will receive an intraoperative periarticular injection consisting of 300mg of 0.5% ropivacaine with 1mg epinephrine and 30mg ketorolac in sodium chloride 0.9% diluted to a volume of 120ml.

DRUG

Adductor Canal Block

Patients randomized to the adductor canal block (ACB) arm will receive a preoperative ACB administered by an anesthesia provider prior to total knee arthroplasty, with additional ropivacaine administered to the posterior capsule per standard protocol.

DRUG

Bupivacaine-Meloxicam

will receive the extended-release bupivacaine injected into the effective knee joint space prior to closure, combined with an abbreviated PAI of half dose (150mg ropivacaine) to act as a bridge per standard recommendation.

Sponsors & Collaborators

• Henry Ford Health System

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-02-11

Primary Completion

2026-10-20

Completion

2026-10-20

FDA Drug

Yes

Countries

• United States

Study Locations