Overview

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.

Eligibility

Inclusion Criteria:

• Adult patients age 18 and older undergoing primary total knee replacement by fellowship trained Orthopedic Surgeons in Henry Ford Health System with planned outpatient same-day discharge.

Exclusion Criteria:

• Incomplete data in medical records
• Non-English speakers
• Chronic opioid use in the last 3 months
• Ipsilateral joint surgery in the last year
• Undergoing bilateral knee arthroplasty
• Cannot tolerate oral medications
• Swallowing difficulties
• Intolerance to acetaminophen, anti-inflammatories, muscle relaxants, gabapentinoids, or opioids/tramadol
• History of alcohol abuse
• Drug abuse
• Renal impairment
• Peptic ulcer disease
• GI bleeding
• Illicit narcotic usage in the past 6 months
• Chronic liver disease
• Chronic pain syndromes