NCT07775248 · Henry Ford Health System
Novel Extended-Release Bupivacaine Polymer for Sustained Pain Relief Following Total Knee Arthroplasty
What this study is about
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).
View original scientific description
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.
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.
Primary outcome measures
Postoperative Pain Score Assessed Using the Numeric Rating Scale (NRS)
Time frame: Postoperative Day 0-Postoperative Day 5
Postoperative pain will be assessed using the Numeric Rating Scale (NRS), an 11-point scale ranging from 0 (no pain) to 10 (worst pain imaginable). Higher scores indicate worse pain outcomes. Pain scores will be recorded daily by participants from postoperative day 0 through postoperative day 5.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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
- Renal impairment
- Peptic ulcer disease
- GI bleeding
- Illicit narcotic usage in the past 6 months
- Chronic liver disease
- Chronic pain syndromes
Where
- Grosse Pointe Farms, Michigan
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Aug 20, 2026 · Source of record for eligibility and locations