Periarticular BlockPhase 4NCT07430085
Post-Operative Pain Relief: Zynrelef or Periarticular Injections in RATKA
A Phase 4 study testing bupivacaine-meloxicam (extended release), Bupivacaine and Ketorolac in people with Periarticular Block and Osteoarthritis (OA), run by Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) at 1 site in United States.
Trial summary
Prospective Cohort of patients who are scheduled for a Robot Assisted Total Knee Arthroplasty (RATKA). A prospective survey of patient reported outcome measures (Numeric Rating Scale) will be obtained postoperatively of 72 hours, as well as at the postoperative opioid consumption after 72 hours. Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- Periarticular Block, Osteoarthritis (OA), Osteoarthritis (OA) of the Knee
- What is being tested?
- bupivacaine-meloxicam (extended release), Bupivacaine and Ketorolac
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Sep 2026to 28 Feb 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females aged 18-89 years
- Diagnosed with knee osteoarthritis requiring surgical intervention
- Indicated for unilateral RATKA
Who cannot join
- Pediatric, pregnant, or incarcerated patients
- BMI of more than 45 kg/m2
- Prolonged opioid use history of >5 mg/day for >1 month
- History of contralateral TKA <2 years prior to the index TKA
- Type 1 Hypersensitivity to NSAIDs or local anesthetics
- Diagnosis of severe renal disease
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
AHN Orthopedic Surgery Cranberry Township
Cranberry Township, Pennsylvania, 16066
Andrew Waligora, MD, 877-660-6777, andrew.waligora2@ahn.org
About this study
Official title: Postoperative Pain Outcomes After Use of Bupivacaine-Meloxicam Extended-Release Solution in Robot Assisted Total Knee Arthroplasty: A Prospective Study
Prospective Cohort of patients who are scheduled for a Robot Assisted Total Knee Arthroplasty (RATKA). A prospective survey of patient reported outcome measures (Numeric Rating Scale) will be obtained postoperatively of 72 hours, as well as at the postoperative opioid consumption after 72 hours.
Read the detailed description
Opioid use is a well-discussed issue in the United States among orthopedic surgeons, as while these drugs are helpful and necessary, they pose the risk of addiction and ultimately should be used as sparingly as possible. By taking a multimodal approach to pain management, this can be successfully achieved. Periarticular injections are currently used to achieve this goal, and 2021 a bupivacaine-meloxicam extended-release periarticular injection (Zynrelef) was introduced and is regularly implemented into RATKAs. Randomized clinical trials found that Zynrelef's use in traditional total knee arthroplasties (TKA) was just as effective as standard periarticular injections in reducing opioid use and pain, but whether Zynrelef works just as well if not better in RATKA is not yet established.
Objectives: (primary and important secondary objectives)
To evaluate the improvement in pain and use of opioids of a patient who received Zynrelef after undergoing RATKA compared to the traditional periarticular injections commonly used. The secondary objective will be documentation of the patient's use of other oral (over-the-counter) OTC pain relievers, such as acetaminophen or NSAIDs (non-steroidal anti inflammatory drugs).
Study Design:
Prospective Cohort Study (double arm)
Setting/Participants:
Patients who have undergone a standard of care RATKA at any Allegheny Health Network facility who consent to filling out a survey addressing their reported outcomes.
Study Interventions and Measures:
Patients will be evaluated with the Numeric Rating Scale (NRS) on postoperative days 1-3. Patients will be given paper forms which will be collected by the physicians at their next postoperative visit. A retrospective review of Epic Electronic Medical Records (EMR) will also be conducted to describe basic demographic characteristics.
- Conditions
- Periarticular Block, Osteoarthritis (OA), Osteoarthritis (OA) of the Knee, Pain After Surgery, Knee Arthroplasty, Total
- Being tested
- bupivacaine-meloxicam (extended release), Bupivacaine, Ketorolac, Lidocaine (drug)
- Keywords
- Zynrelef
- Medical subject headings
- Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bupivacaine-meloxicam (extended release)Combination product
These surgeons will be using Zynrelef (bupivacaine-meloxicam extended release) as a form of periarticular analgesia.
BupivacaineDrug
These surgeons will be using the control injection (bupivacaine + ketorolac + lidocaine) as a form of periarticular analgesia.
KetorolacDrug
These surgeons will be using the control injection (bupivacaine + ketorolac + lidocaine) as a form of periarticular analgesia.
Lidocaine (drug)Drug
These surgeons will be using the control injection (bupivacaine + ketorolac + lidocaine) as a form of periarticular analgesia.
| Study group | Role | What they receive |
|---|---|---|
| Zynrelef | Experimental | Periarticular injection of bupivacaine-meloxicam extended release Receives: Combination Product: bupivacaine-meloxicam (extended release) |
| Control | Active comparator | Periarticular injection of bupivacaine, ketorolac, and lidocaine Receives: Drug: Bupivacaine; Drug: Ketorolac; Drug: Lidocaine (drug) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Amount of opioid medications used (measured in morphine milligrams equivalents)
Self-report of opioid medications
Measured: From completion of surgery to 3 days post-op
Patient reported outcome measure (Numeric Rating Scale)
Self-report of pain using numeric scale. Title: Numeric Rating Scale; Ranges from 0 to 10, where 10 is maximal pain and 0 is no pain at all.
Measured: From completion of surgery to 3 days post-op
Secondary outcomes (2)
Amount of oral Over-the-counter (OTC) pain reliever medications used
Self-report of Over-the-counter (OTC) pain relievers
Measured: From completion of surgery to 3 days post-operation
Complications and Adverse Events
Report of adverse events
Measured: From completion of surgery to 3 days post-op
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2026
- Study start3 Sep 2026
- Primary completion31 Jan 2028 (estimated)
- Study completion28 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Periarticular BlockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrew Waligora, Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
- Investigators
- Andrew Waligora, MD, Principal investigator, Allegheny Health Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07430085
- Sponsor's protocol ID
- 2025-344
- Status last verified
- Oct 2026
- First submitted
- 18 Feb 2026
- Last updated
- 28 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Joo PY, Chen AF, Richards J, Law TY, Taylor K, Marchand K, Clark G, Collopy D, Marchand RC, Roche M, Mont MA, Malkani AL. Clinical results and patient-reported outcomes following robotic-assisted primary total knee arthroplasty : a multicentre study. Bone Jt Open. 2022 Aug;3(8):589-595. doi: 10.1302/2633-1462.37.BJO-2022-0076.R1.
PubMed 35848995Salmons HI, Amundson AW, Duncan CM, Larson DR, Mallinger BD, Couch CG, Pagnano MW, Trousdale RT, Abdel MP. Bupivacaine-Meloxicam Extended-Release Solution Compared with a Standard Periarticular Injection in Primary Total Knee Arthroplasty: A Randomized Clinical Trial Showing Similar Efficacy in Postoperative Analgesia. J Bone Joint Surg Am. 2025 Jul 25;107(17):1918-1925. doi: 10.2106/JBJS.25.00086.
PubMed 40711999Blair HA. Bupivacaine/Meloxicam Prolonged Release: A Review in Postoperative Pain. Drugs. 2021 Jul;81(10):1203-1211. doi: 10.1007/s40265-021-01551-9. Epub 2021 Jul 6.
PubMed 34228280Dydyk AM, Jain NK, Gupta M. Opioid Use Disorder: Evaluation and Management. 2024 Jan 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK553166/
PubMed 31985959Cui A, Li H, Wang D, Zhong J, Chen Y, Lu H. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine. 2020 Nov 26;29-30:100587. doi: 10.1016/j.eclinm.2020.100587. eCollection 2020 Dec.
PubMed 34505846
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Postoperative Pain Outcomes After Use of Bupivacaine-Meloxicam Extended-Release Solution in Robot Assisted Total Knee Arthroplasty: A Prospective Study
- ClinicalTrials.gov ID
- NCT07430085
- Acronym / sponsor ID
- 2025-344
- Conditions
- Periarticular Block, Osteoarthritis (OA), Osteoarthritis (OA) of the Knee, Pain After Surgery, Knee Arthroplasty, Total
- Keywords
- Zynrelef
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)University, hospital or other
- Study start
- 3 Sep 2026 (actual)
- Primary completion
- 31 Jan 2028 (estimated)
- Study completion
- 28 Feb 2028 (estimated)
- First posted
- 24 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prospective Cohort of patients who are scheduled for a Robot Assisted Total Knee Arthroplasty (RATKA). A prospective survey of patient reported outcome measures (Numeric Rating Scale) will be obtained postoperatively of 72 hours, as well as at the postoperative opioid consumption after 72 hours.
Detailed description
Opioid use is a well-discussed issue in the United States among orthopedic surgeons, as while these drugs are helpful and necessary, they pose the risk of addiction and ultimately should be used as sparingly as possible. By taking a multimodal approach to pain management, this can be successfully achieved. Periarticular injections are currently used to achieve this goal, and 2021 a bupivacaine-meloxicam extended-release periarticular injection (Zynrelef) was introduced and is regularly implemented into RATKAs. Randomized clinical trials found that Zynrelef's use in traditional total knee arthroplasties (TKA) was just as effective as standard periarticular injections in reducing opioid use and pain, but whether Zynrelef works just as well if not better in RATKA is not yet established.
Objectives: (primary and important secondary objectives)
To evaluate the improvement in pain and use of opioids of a patient who received Zynrelef after undergoing RATKA compared to the traditional periarticular injections commonly used. The secondary objective will be documentation of the patient's use of other oral (over-the-counter) OTC pain relievers, such as acetaminophen or NSAIDs (non-steroidal anti inflammatory drugs).
Study Design:
Prospective Cohort Study (double arm)
Setting/Participants:
Patients who have undergone a standard of care RATKA at any Allegheny Health Network facility who consent to filling out a survey addressing their reported outcomes.
Study Interventions and Measures:
Patients will be evaluated with the Numeric Rating Scale (NRS) on postoperative days 1-3. Patients will be given paper forms which will be collected by the physicians at their next postoperative visit. A retrospective review of Epic Electronic Medical Records (EMR) will also be conducted to describe basic demographic characteristics.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zynrelef | Experimental | Combination Product: bupivacaine-meloxicam (extended release)Periarticular injection of bupivacaine-meloxicam extended release |
| Control | Active comparator | Drug: Bupivacaine, Drug: Ketorolac, Drug: Lidocaine (drug)Periarticular injection of bupivacaine, ketorolac, and lidocaine |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Males or females aged 18-89 years
- Diagnosed with knee osteoarthritis requiring surgical intervention
- Indicated for unilateral RATKA
Key exclusion criteria (6 listed)
- Pediatric, pregnant, or incarcerated patients
- BMI of more than 45 kg/m2
- Prolonged opioid use history of >5 mg/day for >1 month
- History of contralateral TKA <2 years prior to the index TKA
- Type 1 Hypersensitivity to NSAIDs or local anesthetics
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bupivacaine-meloxicam (extended release)These surgeons will be using Zynrelef (bupivacaine-meloxicam extended release) as a form of periarticular analgesia. | Combination product | Zynrelef |
| BupivacaineThese surgeons will be using the control injection (bupivacaine + ketorolac + lidocaine) as a form of periarticular analgesia. | Drug | Control |
| KetorolacThese surgeons will be using the control injection (bupivacaine + ketorolac + lidocaine) as a form of periarticular analgesia. | Drug | Control |
| Lidocaine (drug)These surgeons will be using the control injection (bupivacaine + ketorolac + lidocaine) as a form of periarticular analgesia. | Drug | Control |
Primary outcome
Amount of opioid medications used (measured in morphine milligrams equivalents)
Time frame: From completion of surgery to 3 days post-op
Self-report of opioid medications
Patient reported outcome measure (Numeric Rating Scale)
Time frame: From completion of surgery to 3 days post-op
Self-report of pain using numeric scale. Title: Numeric Rating Scale; Ranges from 0 to 10, where 10 is maximal pain and 0 is no pain at all.
2 secondary outcomes
Amount of oral Over-the-counter (OTC) pain reliever medications used
Time frame: From completion of surgery to 3 days post-operation
Complications and Adverse Events
Time frame: From completion of surgery to 3 days post-op
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Background: PubMed 35848995Joo PY, Chen AF, Richards J, Law TY, Taylor K, Marchand K, Clark G, Collopy D, Marchand RC, Roche M, Mont MA, Malkani AL. Clinical results and patient-reported outcomes following robotic-assisted primary total knee arthroplasty : a multicentre study. Bone Jt Open. 2022 Aug;3(8):589-595. doi: 10.1302/2633-1462.37.BJO-2022-0076.R1.
- Background: PubMed 40711999Salmons HI, Amundson AW, Duncan CM, Larson DR, Mallinger BD, Couch CG, Pagnano MW, Trousdale RT, Abdel MP. Bupivacaine-Meloxicam Extended-Release Solution Compared with a Standard Periarticular Injection in Primary Total Knee Arthroplasty: A Randomized Clinical Trial Showing Similar Efficacy in Postoperative Analgesia. J Bone Joint Surg Am. 2025 Jul 25;107(17):1918-1925. doi: 10.2106/JBJS.25.00086.
- Background: PubMed 34228280Blair HA. Bupivacaine/Meloxicam Prolonged Release: A Review in Postoperative Pain. Drugs. 2021 Jul;81(10):1203-1211. doi: 10.1007/s40265-021-01551-9. Epub 2021 Jul 6.
- Background: PubMed 31985959Dydyk AM, Jain NK, Gupta M. Opioid Use Disorder: Evaluation and Management. 2024 Jan 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK553166/
- Background: PubMed 34505846Cui A, Li H, Wang D, Zhong J, Chen Y, Lu H. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine. 2020 Nov 26;29-30:100587. doi: 10.1016/j.eclinm.2020.100587. eCollection 2020 Dec.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Andrew Waligora, MD principal investigator
Allegheny Health Network
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing bupivacaine-meloxicam (extended release), Bupivacaine and Ketorolac in people with Periarticular Block and Osteoarthritis (OA), run by Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Obinna Ajah, MD (877-660-6777, obinna.ajah@ahn.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Amount of opioid medications used (measured in morphine milligrams equivalents) (time frame: From completion of surgery to 3 days post-op). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07430085, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.