Total Knee ArthroplastyPhase 4CRS-121NCT07584915

Pilot Study on EXPAREL as an Intra-articular Posteromedial Surgeon Administered (IPSA) Block vs. Local Infiltration Analgesia in Knee Replacement Surgery

A Phase 4 study testing Intra-articular Posteromedial Surgeon Administered (IPSA) Block with LIA, Local Infiltration Analgesia (LIA) and Bupivacaine liposome injectable suspension (IPSA block) in people with Total Knee Arthroplasty and Total Knee Arthroplasty Recovery, run by Cedars-Sinai Medical Center at 1 site in United States.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts

Official record

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Trial summary

The study aims to test the safety and effectiveness of two different surgeon-administered methods of the anesthesia medication EXPAREL during knee replacement surgery. This study will not determine whether one method is better than the other, but will instead help the study investigator decide if both methods can… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Total Knee Arthroplasty, Total Knee Arthroplasty Recovery
What is being tested?: Intra-articular Posteromedial Surgeon Administered (IPSA) Block with LIA, Local Infiltration Analgesia (LIA) and Bupivacaine liposome injectable suspension (IPSA block)
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 40 participants
Where: 1 siteUnited States
Study dates: 1 Jun 2026to Aug 2026
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

18 years of age or older
Scheduled to undergo total knee arthroplasty (TKA) under spinal anesthesia
Primary indication for TKA is degenerative osteoarthritis of the knee
Able to provide informed consent, adhere to the study schedule, and complete all study assessments
Body Mass Index (BMI) ≥18 and <40 kg/m2

Who cannot join

Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications for which an alternative is not named in the protocol (e.g., amide-type local anesthetics, opioids, bupivacaine HCl, NSAIDs)
Planned concurrent surgical procedure
Undergoing knee surgery for a single area of the knee or a revision surgery
History of knee replacement surgery within the past 6 months
History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years
Previous participation in an EXPAREL study

Show all 13Show fewer

Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, could interfere with study assessments or compliance
Currently pregnant, nursing, or planning to become pregnant during the study
Any individual who, per standard of care, is excluded from the surgery due to possibility of pregnancy.
Male participant in a sexually active relation with pregnant or breastfeeding partner
Clinically significant medical disease that, in the opinion of the Investigator, would make participation in a clinical study inappropriate.
Any use of marijuana [including Tetrahydrocannabinol (THC) and Cannabidiol (CBD)] within 30 days prior to randomization, or planned use during the course of the study
Chronic opioid use within 30 days prior to surgery

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

Cedars-Sinai Medical Center
Los Angeles, California, 90048

Other trials in United States

About this study

Official title: A Prospective, Single-Center, Randomized, Pilot Study to Assess the Clinical Effectiveness of EXPAREL as an Intra-articular Posteromedial Surgeon Administered (IPSA) Block Compared to Local Infiltration Analgesia in Subjects Undergoing Primary Unilateral Total Knee Arthroplasty

The main question this study aims to answer is:

Will EXPAREL provide an equal amount of pain relief for patients who receive EXPAREL via Intra-articular Posteromedial Surgeon Administered (IPSA) Block and patients that receive EXPAREL via Local Infiltration Analgesia (LIA)?

Following their surgery, participants will be asked to report their pain level on their treated knee using a numerical rating scale (NRS) between 0 to 10. In addition to their pain level, participants will report any medications used for pain relief and will mark specific regions on an image to indicate where they experience pain.

Conditions: Total Knee Arthroplasty, Total Knee Arthroplasty Recovery
Being tested: Intra-articular Posteromedial Surgeon Administered (IPSA) Block with LIA, Local Infiltration Analgesia (LIA), Bupivacaine liposome injectable suspension (IPSA block), Bupivacaine liposome injectable suspension (LIA)
Keywords: intra-articular posteromedial, local infiltration analgesia, knee replacement surgery, EXPAREL

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Intra-articular Posteromedial Surgeon Administered (IPSA) Block with LIAProcedure or surgery
The IPSA block is a specific surgeon technique which involves providing an injection of EXPAREL to the back of the knee, reaching into the joint space to provide pain relief. This arm will also receive the LIA procedure.
Local Infiltration Analgesia (LIA)Procedure or surgery
The local infiltration analgesia (LIA) procedure involves the administration of anesthesia with the use of several needle sticks to areas surrounding the knee joint.
Bupivacaine liposome injectable suspension (IPSA block)Drug
Group 1 will be given an IPSA block using 10 mL of EXPAREL mixed with 10 mL of bupivacaine HCl 0.5%. An injection around the knee joint will be given as well utilizing a cocktail of: 10 mL of EXPAREL, 10 mL of bupivacaine HCl 0.5%, and 40 mL normal saline.
Bupivacaine liposome injectable suspension (LIA)Drug
Group 2 will be given LIA with EXPAREL 20 mL (266 mg) mixed with 20 mL bupivacaine HCL 0.5% and 80 mL normal saline (total volume of 120 mL).

Study groups in NCT07584915
Study group	Role	What they receive
Group 1 - Study Group	Experimental	Group 1 will be assigned to receive the IPSA Block which is an innovative surgeon technique to administer anesthesia to a treated knee joint and will include the standard technique known as Local Infiltration Analgesia (LIA). Receives: Procedure: Intra-articular Posteromedial Surgeon Administered (IPSA) Block with LIA; Drug: Bupivacaine liposome injectable suspension (IPSA block)
Group 2 - Control Group	Active comparator	Group 2 will be assigned to receive Local Infiltration Analgesia (LIA) which is the standard anesthesia administration technique used for patients undergoing knee replacement surgery. Receives: Procedure: Local Infiltration Analgesia (LIA); Drug: Bupivacaine liposome injectable suspension (LIA)

What is being measured

The primary outcome is the main question the study is designed to answer.

Post-Operative Pain Scores
The primary outcome measure will be the Numerical Rating Scale (NRS) pain intensity scores reported by study participants. These results will be compared between both treatment groups.
Measured: Study participants will report Numerical Rating Scale (NRS) pain intensity scores throughout various timepoints between 0 to 72 hours post-surgery.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jun 2026Aug 2026

First posted13 May 2026
Study start1 Jun 2026 (estimated)
Primary completionAug 2026 (estimated)
Study completionAug 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Total Knee ArthroplastyStudies of the same condition, open and under way.
More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
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
Model description: Both treatment groups will receive the same anesthesia medication (EXPAREL), but each group will receive the medication in a different way. Each group will be assigned a different surgeon-administered anesthesia technique.
Masking: Single blind
Who is masked: Participant
Enrolment: 40 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07584915
Sponsor's protocol ID: Pro00003735
Acronym: CRS-121
Status last verified: Mar 2026
First submitted: 7 May 2026
Last updated: 13 May 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: All de-identified IPD related to the study protocol will be shared.

Publications

Piuzzi NS, Spitzer AI, Mussell J, Pasqualini I, Dysart S, Gonzales J, Mont MA, Lonner JH, Mihalko W. Validation of a Novel Landmark-guided Intra-articular Postero-medial Surgeon-administered Injection Technique. Arthroplast Today. 2025 Jan 25;31:101619. doi: 10.1016/j.artd.2025.101619. eCollection 2025 Feb.
PubMed 39927121
Dysart SH, Barrington JW, Del Gaizo DJ, Sodhi N, Mont MA. Local Infiltration Analgesia With Liposomal Bupivacaine Improves Early Outcomes After Total Knee Arthroplasty: 24-Hour Data From the PILLAR Study. J Arthroplasty. 2019 May;34(5):882-886.e1. doi: 10.1016/j.arth.2018.12.026. Epub 2018 Dec 25.
PubMed 30799269
Mont MA, Beaver WB, Dysart SH, Barrington JW, Del Gaizo DJ. Local Infiltration Analgesia With Liposomal Bupivacaine Improves Pain Scores and Reduces Opioid Use After Total Knee Arthroplasty: Results of a Randomized Controlled Trial. J Arthroplasty. 2018 Jan;33(1):90-96. doi: 10.1016/j.arth.2017.07.024. Epub 2017 Jul 25.
PubMed 28802777
Dysart S, Snyder MA, Mont MA. A Randomized, Multicenter, Double-Blind Study of Local Infiltration Analgesia with Liposomal Bupivacaine for Postsurgical Pain Following Total Knee Arthroplasty: Rationale and Design of the Pillar Trial. Surg Technol Int. 2016 Nov 11;30:261-267.
PubMed 27824434

Interested in taking part?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

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SII Levels Following iPACK Block With Adductor Canal Block in Knee Arthroplasty
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Enrolling by invitationObservational study
Persona SoluTion PPS Femur PMCF
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ACB and iPACK Blocks With Intravenous Dexamethasone and Perineural Dexmedetomidine in Total Knee Arthroplasty
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RecruitingPhase 3
REGN7508 Versus Acetylsalicylic Acid (ASA) for Venous Thromboprophylaxis After Total Knee Arthroplasty in Adult Participants
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All Total Knee Arthroplasty trials

Study at a glance

From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Prospective, Single-Center, Randomized, Pilot Study to Assess the Clinical Effectiveness of EXPAREL as an Intra-articular Posteromedial Surgeon Administered (IPSA) Block Compared to Local Infiltration Analgesia in Subjects Undergoing Primary Unilateral Total Knee Arthroplasty
ClinicalTrials.gov ID: NCT07584915
Acronym / sponsor ID: CRS-121 / Pro00003735
Conditions: Total Knee Arthroplasty, Total Knee Arthroplasty Recovery
Keywords: intra-articular posteromedial, local infiltration analgesia, knee replacement surgery, EXPAREL
Phase: Phase 4
Study type: Interventional
Recruitment status: Enrolling by invitation
Enrolment: 40 participants (estimated)
Lead sponsor: Cedars-Sinai Medical CenterUniversity, hospital or other
Collaborators: Pacira Pharmaceuticals, Inc
Study start: 1 Jun 2026 (estimated)
Primary completion: Aug 2026 (estimated)
Study completion: Aug 2026 (estimated)
First posted: 13 May 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.

The main question this study aims to answer is:

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (participant)
Number of arms: 2
Model description: Both treatment groups will receive the same anesthesia medication (EXPAREL), but each group will receive the medication in a different way. Each group will be assigned a different surgeon-administered anesthesia technique.

Arm	Type	Receives
Group 1 - Study Group	Experimental	Procedure: Intra-articular Posteromedial Surgeon Administered (IPSA) Block with LIA, Drug: Bupivacaine liposome injectable suspension (IPSA block)Group 1 will be assigned to receive the IPSA Block which is an innovative surgeon technique to administer anesthesia to a treated knee joint and will include the standard technique known as Local Infiltration Analgesia (LIA).
Group 2 - Control Group	Active comparator	Procedure: Local Infiltration Analgesia (LIA), Drug: Bupivacaine liposome injectable suspension (LIA)Group 2 will be assigned to receive Local Infiltration Analgesia (LIA) which is the standard anesthesia administration technique used for patients undergoing knee replacement surgery.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

18 years of age or older
Scheduled to undergo total knee arthroplasty (TKA) under spinal anesthesia
Primary indication for TKA is degenerative osteoarthritis of the knee
Able to provide informed consent, adhere to the study schedule, and complete all study assessments
Body Mass Index (BMI) ≥18 and <40 kg/m2

Key exclusion criteria (13 listed)

Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications for which an alternative is not named in the protocol (e.g., amide-type local anesthetics, opioids, bupivacaine HCl, NSAIDs)
Planned concurrent surgical procedure
Undergoing knee surgery for a single area of the knee or a revision surgery
History of knee replacement surgery within the past 6 months
History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years

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
Intra-articular Posteromedial Surgeon Administered (IPSA) Block with LIAThe IPSA block is a specific surgeon technique which involves providing an injection of EXPAREL to the back of the knee, reaching into the joint space to provide pain relief. This arm will also receive the LIA procedure.	Procedure or surgery	Group 1 - Study Group
Local Infiltration Analgesia (LIA)The local infiltration analgesia (LIA) procedure involves the administration of anesthesia with the use of several needle sticks to areas surrounding the knee joint.	Procedure or surgery	Group 2 - Control Group
Bupivacaine liposome injectable suspension (IPSA block)Group 1 will be given an IPSA block using 10 mL of EXPAREL mixed with 10 mL of bupivacaine HCl 0.5%. An injection around the knee joint will be given as well utilizing a cocktail of: 10 mL of EXPAREL, 10 mL of bupivacaine HCl 0.5%, and 40 mL normal saline.	Drug	Group 1 - Study Group
Bupivacaine liposome injectable suspension (LIA)Group 2 will be given LIA with EXPAREL 20 mL (266 mg) mixed with 20 mL bupivacaine HCL 0.5% and 80 mL normal saline (total volume of 120 mL).	Drug	Group 2 - Control Group

Primary outcome

Post-Operative Pain Scores
Time frame: Study participants will report Numerical Rating Scale (NRS) pain intensity scores throughout various timepoints between 0 to 72 hours post-surgery.
The primary outcome measure will be the Numerical Rating Scale (NRS) pain intensity scores reported by study participants. These results will be compared between both treatment groups.

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 13 May 2026.
Background: PubMed 39927121Piuzzi NS, Spitzer AI, Mussell J, Pasqualini I, Dysart S, Gonzales J, Mont MA, Lonner JH, Mihalko W. Validation of a Novel Landmark-guided Intra-articular Postero-medial Surgeon-administered Injection Technique. Arthroplast Today. 2025 Jan 25;31:101619. doi: 10.1016/j.artd.2025.101619. eCollection 2025 Feb.
Background: PubMed 30799269Dysart SH, Barrington JW, Del Gaizo DJ, Sodhi N, Mont MA. Local Infiltration Analgesia With Liposomal Bupivacaine Improves Early Outcomes After Total Knee Arthroplasty: 24-Hour Data From the PILLAR Study. J Arthroplasty. 2019 May;34(5):882-886.e1. doi: 10.1016/j.arth.2018.12.026. Epub 2018 Dec 25.
Background: PubMed 28802777Mont MA, Beaver WB, Dysart SH, Barrington JW, Del Gaizo DJ. Local Infiltration Analgesia With Liposomal Bupivacaine Improves Pain Scores and Reduces Opioid Use After Total Knee Arthroplasty: Results of a Randomized Controlled Trial. J Arthroplasty. 2018 Jan;33(1):90-96. doi: 10.1016/j.arth.2017.07.024. Epub 2017 Jul 25.
Background: PubMed 27824434Dysart S, Snyder MA, Mont MA. A Randomized, Multicenter, Double-Blind Study of Local Infiltration Analgesia with Liposomal Bupivacaine for Postsurgical Pain Following Total Knee Arthroplasty: Rationale and Design of the Pillar Trial. Surg Technol Int. 2016 Nov 11;30:261-267.
Individual participant dataSharing planned: Yes. All de-identified IPD related to the study protocol will be shared.

Related trials for Total Knee Arthroplasty

RecruitingPhase 3
REGN7508 Versus Apixaban and Enoxaparin for Thromboprophylaxis After Total Knee Arthroplasty in Adults
Venous Thromboembolism (VTE)
Recruiting
SII Levels Following iPACK Block With Adductor Canal Block in Knee Arthroplasty
Knee Osteoarthritis
Enrolling by invitationObservational study
Persona SoluTion PPS Femur PMCF
Rhematoid Arthritis, Osteo Arthritis of the Knee
Recruiting
ACB and iPACK Blocks With Intravenous Dexamethasone and Perineural Dexmedetomidine in Total Knee Arthroplasty
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RecruitingPhase 3
REGN7508 Versus Acetylsalicylic Acid (ASA) for Venous Thromboprophylaxis After Total Knee Arthroplasty in Adult Participants
Symptomatic Venous Thromboembolism (VTE)

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 I Spitzer, MD principal investigator

Cedars-Sinai Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 5 inclusion and 13 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: enrolling by invitation, as of the sponsor's last update on 13 May 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Post-Operative Pain Scores (time frame: Study participants will report Numerical Rating Scale (NRS) pain intensity scores throughout various timepoints between 0 to 72 hours post-surgery.). 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 NCT07584915, which also lists 4 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 13 May 2026.