Trial Outcomes & Findings for Periarticular Bupivacaine + Meloxicam ER Solution Versus Standard Practice During Total Knee Arthroplasty (NCT NCT05188053)

Results Overview

Area Under the Curve (AUC) of the graph for mean Numerical Rated Score (NRS) for pain (0-10) over time (0-72 hours) / NRS AUC 0-72. Pain scores were collected by patient self-report 15 times over the 72 hours after surgery, and averaged amongst the patients for each study arm. Lower values represent better pain control based on lower mean 0-10 pain scores over the 72 hour period after surgery. The minimum value is 0, meaning patients reported 0 pain on a 0-10 scale at all 15 time points within 72 hours. The maximum value would be 720, meaning patients reported a 10 for pain on a 0-10 scale at all 15 time points within 72 hours.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

209 participants

Primary outcome timeframe

72-hours postoperatively after total knee arthroplasty

Results posted on

2025-04-27

Participant Flow

Recruitment for this study ran from 3/11/2022 until 4/9/2024 when the final patient was enrolled. Patients were enrolled from the Orthopedic clinical practice at Mayo Clinic.

An initial pilot of 18 patients ran from 3/11/2022 to 8/30/2022 after which a protocol change caused these patients to be withdrawn and not assigned to a treatment arm in the final study count. One additional patient was withdrawn prior to randomization as allergy results returned which excluded participation.

Participant milestones

Participant milestones
Measure	HTX-011 Treatment Group Subjects undergoing a total knee arthroplasty will receive HTX-011 (Zynrelef) for perioperative analgesia HTX-011: Single dose administration periarticular 400mg bupivacaine and 12mg meloxicam extended release solution	Standard Block Control Group Subjects undergoing a total knee arthroplasty will receive standard of care arthroplasty block for perioperative analgesia ropivacaine , epinephrine , ketorolac diluted in sodium chloride: Single dose administration in 100cc of standard formulation, there is 225mg of ropivacaine 5mg/mL, 0.6mg epinephrine 1mg/mL, 30mg ketorolac 30mg/mL diluted in sodium chloride
Overall Study STARTED	95	95
Overall Study COMPLETED	53	48
Overall Study NOT COMPLETED	42	47

Reasons for withdrawal

Reasons for withdrawal
Measure	HTX-011 Treatment Group Subjects undergoing a total knee arthroplasty will receive HTX-011 (Zynrelef) for perioperative analgesia HTX-011: Single dose administration periarticular 400mg bupivacaine and 12mg meloxicam extended release solution	Standard Block Control Group Subjects undergoing a total knee arthroplasty will receive standard of care arthroplasty block for perioperative analgesia ropivacaine , epinephrine , ketorolac diluted in sodium chloride: Single dose administration in 100cc of standard formulation, there is 225mg of ropivacaine 5mg/mL, 0.6mg epinephrine 1mg/mL, 30mg ketorolac 30mg/mL diluted in sodium chloride
Overall Study Lost to Follow-up	23	30
Overall Study Protocol Violation	16	16
Overall Study Physician Decision	3	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HTX-011 Treatment Group n=95 Participants Subjects undergoing a total knee arthroplasty will receive HTX-011 (Zynrelef) for perioperative analgesia HTX-011: Single dose administration periarticular 400mg bupivacaine and 12mg meloxicam extended release solution	Standard Block Control Group n=95 Participants Subjects undergoing a total knee arthroplasty will receive standard of care arthroplasty block for perioperative analgesia ropivacaine , epinephrine , ketorolac diluted in sodium chloride: Single dose administration in 100cc of standard formulation, there is 225mg of ropivacaine 5mg/mL, 0.6mg epinephrine 1mg/mL, 30mg ketorolac 30mg/mL diluted in sodium chloride	Total n=190 Participants Total of all reporting groups
Age, Continuous	69.6 years STANDARD_DEVIATION 8.1 • n=95 Participants	69.9 years STANDARD_DEVIATION 8.6 • n=95 Participants	69.7 years STANDARD_DEVIATION 8.3 • n=190 Participants
Sex: Female, Male Female	54 Participants n=95 Participants	54 Participants n=95 Participants	108 Participants n=190 Participants
Sex: Female, Male Male	41 Participants n=95 Participants	41 Participants n=95 Participants	82 Participants n=190 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: 72-hours postoperatively after total knee arthroplasty

Area Under the Curve (AUC) of the graph for mean Numerical Rated Score (NRS) for pain (0-10) over time (0-72 hours) / NRS AUC 0-72. Pain scores were collected by patient self-report 15 times over the 72 hours after surgery, and averaged amongst the patients for each study arm. Lower values represent better pain control based on lower mean 0-10 pain scores over the 72 hour period after surgery. The minimum value is 0, meaning patients reported 0 pain on a 0-10 scale at all 15 time points within 72 hours. The maximum value would be 720, meaning patients reported a 10 for pain on a 0-10 scale at all 15 time points within 72 hours.

Outcome measures

Outcome measures
Measure	HTX-011 Treatment Group n=53 Participants Subjects undergoing a total knee arthroplasty will receive HTX-011 (Zynrelef) for perioperative analgesia HTX-011: Single dose administration periarticular 400mg bupivacaine and 12mg meloxicam extended release solution	Standard Block Control Group n=48 Participants Subjects undergoing a total knee arthroplasty will receive standard of care arthroplasty block for perioperative analgesia ropivacaine , epinephrine , ketorolac diluted in sodium chloride: Single dose administration in 100cc of standard formulation, there is 225mg of ropivacaine 5mg/mL, 0.6mg epinephrine 1mg/mL, 30mg ketorolac 30mg/mL diluted in sodium chloride
Pain Control at 72 Hours Postoperatively	334 score on a scale * hours Standard Deviation 16	370 score on a scale * hours Standard Deviation 21

SECONDARY outcome

Timeframe: 48-hours postoperative total knee arthroplasty

Area Under the Curve (AUC) of the graph for mean Numerical Rated Score (NRS) for pain (0-10) over time (0-48 hours) / NRS AUC 0-48. Pain scores were collected by patient self-report 11 times over the 48 hours after surgery, and averaged amongst the patients for each study arm. Lower values represent better pain control based on lower mean 0-10 pain scores over the 48 hour period after surgery. The minimum value is 0, meaning patients reported 0 pain on a 0-10 scale at all 11 time points within 48 hours. The maximum value would be 480, meaning patients reported a 10 for pain on a 0-10 scale at all 11 time points within 48 hours

Outcome measures

Outcome measures
Measure	HTX-011 Treatment Group n=53 Participants Subjects undergoing a total knee arthroplasty will receive HTX-011 (Zynrelef) for perioperative analgesia HTX-011: Single dose administration periarticular 400mg bupivacaine and 12mg meloxicam extended release solution	Standard Block Control Group n=48 Participants Subjects undergoing a total knee arthroplasty will receive standard of care arthroplasty block for perioperative analgesia ropivacaine , epinephrine , ketorolac diluted in sodium chloride: Single dose administration in 100cc of standard formulation, there is 225mg of ropivacaine 5mg/mL, 0.6mg epinephrine 1mg/mL, 30mg ketorolac 30mg/mL diluted in sodium chloride
Pain Control at 48 Hours Postoperatively	237 score on a scale * hours Standard Deviation 14	268 score on a scale * hours Standard Deviation 13

SECONDARY outcome

Timeframe: 72-hours postoperative total knee arthroplasty

Population: patient who returned a complete pain diary

Total postoperative opioid consumption standardized into morphine milligram equivalents (MMEs)

Outcome measures

Outcome measures
Measure	HTX-011 Treatment Group n=53 Participants Subjects undergoing a total knee arthroplasty will receive HTX-011 (Zynrelef) for perioperative analgesia HTX-011: Single dose administration periarticular 400mg bupivacaine and 12mg meloxicam extended release solution	Standard Block Control Group n=48 Participants Subjects undergoing a total knee arthroplasty will receive standard of care arthroplasty block for perioperative analgesia ropivacaine , epinephrine , ketorolac diluted in sodium chloride: Single dose administration in 100cc of standard formulation, there is 225mg of ropivacaine 5mg/mL, 0.6mg epinephrine 1mg/mL, 30mg ketorolac 30mg/mL diluted in sodium chloride
Opioid Consumption 72 Hours Postoperatively	85 MME Interval 0.0 to 238.0	77 MME Interval 0.0 to 163.0

SECONDARY outcome

Timeframe: 48 hours postoperative total knee arthroplasty

Population: patients who returned a completed pain diary

Total postoperative opioid consumption standardized into morphine milligram equivalents (MMEs)

Outcome measures

Outcome measures
Measure	HTX-011 Treatment Group n=53 Participants Subjects undergoing a total knee arthroplasty will receive HTX-011 (Zynrelef) for perioperative analgesia HTX-011: Single dose administration periarticular 400mg bupivacaine and 12mg meloxicam extended release solution	Standard Block Control Group n=48 Participants Subjects undergoing a total knee arthroplasty will receive standard of care arthroplasty block for perioperative analgesia ropivacaine , epinephrine , ketorolac diluted in sodium chloride: Single dose administration in 100cc of standard formulation, there is 225mg of ropivacaine 5mg/mL, 0.6mg epinephrine 1mg/mL, 30mg ketorolac 30mg/mL diluted in sodium chloride
Opioid Consumption 48 Hours Postoperatively	67 MME Interval 0.0 to 163.0	60 MME Interval 0.0 to 182.0

Adverse Events

HTX-011 Treatment Group

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Standard Block Control Group

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	HTX-011 Treatment Group n=53 participants at risk Subjects undergoing a total knee arthroplasty will receive HTX-011 (Zynrelef) for perioperative analgesia HTX-011: Single dose administration periarticular 400mg bupivacaine and 12mg meloxicam extended release solution	Standard Block Control Group n=48 participants at risk Subjects undergoing a total knee arthroplasty will receive standard of care arthroplasty block for perioperative analgesia ropivacaine , epinephrine , ketorolac diluted in sodium chloride: Single dose administration in 100cc of standard formulation, there is 225mg of ropivacaine 5mg/mL, 0.6mg epinephrine 1mg/mL, 30mg ketorolac 30mg/mL diluted in sodium chloride
Gastrointestinal disorders Nausea	1.9% 1/53 • Number of events 1 • Adverse event data was collected from patient consent until 72 hours postoperatively.	2.1% 1/48 • Number of events 1 • Adverse event data was collected from patient consent until 72 hours postoperatively.
Nervous system disorders Seizure	0.00% 0/53 • Adverse event data was collected from patient consent until 72 hours postoperatively.	2.1% 1/48 • Number of events 1 • Adverse event data was collected from patient consent until 72 hours postoperatively.

Additional Information

Gabriel Schouten - Clinical Research Coordinator

Mayo Clinic

Phone: 507-266-5895

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place