A Phase 4 interventional study of Intra-articular injection of bupivacaine in the knee joint and intra-articular injection of Exparel in the knee joint in Total Knee Anthroplasty, sponsored by Foundation for Orthopaedic Research and Education. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years to 90 Years. Per ClinicalTrials.gov, last updated 2026-10-16.
Sponsored by Foundation for Orthopaedic Research and Education · Phase 4, Interventional, and Treatment
This study looks at how three different numbing injections affect how quickly patients recover after knee replacement surgery (total knee arthroplasty, or TKA). Pain after knee replacement is common and can slow down how soon patients get moving again. Doctors often inject a numbing medication around the knee during surgery to help control this pain, but it is not clear which medication helps patients recover fastest in the first few days after surgery.
The study compares three injections that are all FDA approved and already used as part of routine knee replacement care: Exparel (liposomal bupivacaine), Zynrelef (bupivacaine with meloxicam), and Marcaine (bupivacaine). Exparel and Zynrelef are the two groups being studied, and Marcaine is the comparison (control) group.
Adults who are already planning to have a knee replacement may take part. People who join are placed into one of the three injection groups at random, so each person has a one in three chance of receiving each injection. Patients are not told which injection they received. Everything else about the surgery, anesthesia, and recovery care stays the same as usual.
The main goal is to see which injection helps patients recover best in the first three days after surgery. To measure recovery, the study team collects information on pain, pain-medication use, knee motion, activity level, and function. Patients complete short questionnaires about their activity, pain, and quality of life at their regular visits (before surgery and at 3 days, 1 week, 2 weeks, 6 weeks, 3 months, 1 year, and 2 years). A smart knee implant also records information about knee movement and motion at 3 and 7 days after surgery. About 200 people will take part. The study is considered minimal risk, meaning the risks are similar to those of having a knee replacement outside of the study.
Foundation for Orthopaedic Research and Education is the lead sponsor of 17 studies on the registry; 4 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
These patients will receive Exparel as their Intra-articular injection
Drug: intra-articular injection of Exparel in the knee joint
These patients will receive Zynrelef as their Intra-articular injection
Drug: Zynrelef
These patients will receive Bupivicaine as their Intra-articular injection
Drug: Intra-articular injection of bupivacaine in the knee joint
The intervention is the use of bupivacaine for the intra-articular injection
The intervention is the intra-articular injection of Exparel in the knee joint
The intervention is the use of Zynbrelef for the intra-articular injection
Early Functional Recovery
To compare the rate of early functional recovery during the first 3 postoperative days, measured as the change/improvement over time in objective gait metrics and daily total qualified step count, between the Exparel group, Zynrelef group, and the bupivacaine hydrochloride alone group.
Time frame: First 3 days post-op
ROM
To compare the rate of improvement in knee/functional range of motion (ROM) at 1 week post-operatively and out to 2 years post-operatively
Time frame: Up to 2 years post-operatively
Visual Analogue Scale
To compare postoperative pain scores (VAS/numeric). The scale is from 0-10 with higher scores indicating greater pain.
Time frame: 2 years post-op
Opioid Consumption
To compare cumulative opioid consumption (oral morphine equivalents)
Time frame: 2 years post-op
Knee Injury and Osteoarthritis Outcome Score (KOOS) - Pain
To compare the KOOS Pain subscale is from 0-100 with higher scores meaning worse knee problems
Time frame: 2 years post-operatively
Knee Injury and Osteoarthritis Outcome Score (KOOS) - Symptoms
To compare the KOOS Symptoms subscale, which is from 0-100 with higher scores meaning worse knee problems
Time frame: 2 years post-operatively
Knee Injury and Osteoarthritis Outcome Score (KOOS) - Function
To compare the KOOS Function subscale, which is from 0-100 with higher scores meaning worse knee problems
Time frame: 2 years post-operatively
Knee Injury and Osteoarthritis Outcome Score (KOOS) - Sport & Recreation
To compare the KOOS Sport \& Recreation subscale, which is from 0-100 with higher scores meaning worse knee problems
Time frame: 2 years post-operatively
Knee Injury and Osteoarthritis Outcome Score (KOOS) - Quality of Life
To compare the KOOS Quality of Life subscale, which is from 0-100 with higher scores meaning worse knee problems
Time frame: 2 years post-operatively
Knee Society Score (KSS)
To compare the KSS score - Scale is from 0-100 with higher scores meaning fewer knee problems
Time frame: 2 years post-operatively
UCLA Activity Score
To compare the UCLA Activity Score is from 1-10 with higher scores meaning higher levels of activity
Time frame: 2 years post-operatively
Tegner Activity Score
To compare the Tegner Activity Score is from 0-10 with higher scores meaning higher levels of activity
Time frame: 2 years post-operatively
5-level EQ-5D version (EQ-5D-5L) Quality of Life Score
To compare the EQ-5D-5L Quality of Life Score is from 1-10 with higher scores meaning higher levels problem severity
Time frame: 2 years post-operatively
Age
Explore whether age modifies early recovery within and across groups.
Time frame: 2 years
Sex
To compare whether sex modifies early recovery within and across groups.
Time frame: 2 years post-op
Height
To explore whether height modifies early recovery within and across groups.
Time frame: 2 years
Weight
To explore whether weight modifies early recovery within and across groups.
Time frame: 2 years
BMI
To explore whether BMI modifies early recovery within and across groups, by combining patient height (cm) and weight (kg).
Time frame: 2 years post-op
Cost
To compare the overall cost of injection for patients across each group.
Time frame: 2 years post-opb
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No — Individual participant data will not be shared with researchers outside the study team. The study collects identifiable clinical data as part of routine total knee arthroplasty care, and participants consent to its use only for this study. As stated in the informed consent, participant data will not be used or distributed for future research studies, even with identifiers removed. Any future sharing would require a separate protocol and IRB approval, along with participant re-consent where applicable.
Start is estimated for Oct 2026; primary completion for Dec 2027, 14 months later.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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Foundation for Orthopaedic Research and Education