Knee OsteoarthritisPhase 2/3TKACSINCT07151417
Use of Corticosteroid in Intraopertive Injections in Total Knee Replacement Surgery.
A Phase 2/3 study testing PAI, PAI + steroid and PAI + zilretta in people with Knee Osteoarthritis and Musculoskeletal Disease, run by Walter Reed National Military Medical Center at 1 site in United States.
Trial summary
The goal of this clinical trial is to find out which type of steroid medicine, when added to a standard pain-control injection during total knee replacement surgery, works best at reducing pain, limiting opioid use, and improving recovery in adults undergoing surgery for severe knee arthritis or injury. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Knee Osteoarthritis, Musculoskeletal Disease, Surgery
- What is being tested?
- PAI, PAI + steroid and PAI + zilretta
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2026to 31 Aug 2027
- Phase
- Phase 2/3
- 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
- Patients within the MHS who are DEERS eligible undergoing primary TKA at Walter Reed National Military Medical Center (WRNMMC), Surgery Center of Chevy Chase or District Surgery Center
- Age 18 or older
- successful surgical intervention
Who cannot join
- Unicompartmental knee arthroplasty (UKA)
- Revision total knee arthroplasty (rTKA)
- Females who are pregnant or nursing
- Allergic to ingredients in PAI or previous adverse reaction to steroids being used in this study
- Diabetics will be excluded from Group 2 (standard PAI + methylprednisolone)
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
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889
John P Cody, MD, 301-538-2472, john.p.cody3.mil@health.mil
Garrett Neel, MD
About this study
Official title: Adjunctive Use of Corticosteroid in Periarticular Injections in Primary Total Knee Arthroplasty
The goal of this clinical trial is to find out which type of steroid medicine, when added to a standard pain-control injection during total knee replacement surgery, works best at reducing pain, limiting opioid use, and improving recovery in adults undergoing surgery for severe knee arthritis or injury.
The main questions it aims to answer are:
Read more
Does adding a steroid to the injection improve pain control and reduce opioid use after surgery? Is the newer extended-release steroid (Zilretta) more effective and safer-especially for patients with diabetes-than the traditional steroid (methylprednisolone)?
Researchers will compare:
Standard pain-control injection alone Standard injection plus methylprednisolone Standard injection plus Zilretta to see which option provides better pain relief, less opioid use, and improved knee function.
(Patients with diabetes or prediabetes will only be in the standard injection or Zilretta groups so researchers can study whether Zilretta is safer for blood sugar control.)
Participants will:
Be randomly assigned to one of the study groups during their total knee replacement surgery Receive the assigned pain-control injection around the knee joint
Be followed after surgery to measure:
Pain levels Opioid pain medication use Knee movement (range of motion) Whether another procedure (such as manipulation under anesthesia) is needed if the knee becomes too stiff Patient-reported outcome surveys about pain and function
Read the detailed description
Total knee replacement surgery (also called total knee arthroplasty, or TKA) is a common procedure for people with severe knee arthritis or injury. While the surgery often leads to significant pain relief and improved mobility, the days and weeks afterward can be uncomfortable. Managing pain during recovery is important-not just to make patients feel better, but also to help them move their knee sooner, avoid excessive use of opioid medications, and get back to normal activities faster.
One common pain management tool is called a pericapsular injection (PAI). This is a mixture of medications injected around the knee joint during surgery to help control pain after the operation. PAIs usually include a long-lasting numbing medicine, an anti-inflammatory drug, and sometimes other medications that improve pain relief. Corticosteroids-powerful anti-inflammatory drugs-are sometimes added, but the best type of steroid and the ideal way to give it is still debated among doctors.
Why This Study Is Being Done This study will compare two types of corticosteroids, methylprednisolone (a traditional steroid) and Zilretta (a newer, extended-release form of the steroid triamcinolone), to see which works better when added to the standard PAI. Zilretta releases medication slowly over time, which may lead to longer-lasting pain control and fewer side effects such as temporary increases in blood sugar-something especially important for people with diabetes.
How the Study Works
Patients having total knee replacement will be randomly placed into one of three groups:
- Standard PAI only - This mixture includes a long-acting numbing medicine, an anti-inflammatory (ketorolac), a small dose of adrenaline (epinephrine), clonidine (to help with pain control), and sterile saline.
- Standard PAI + methylprednisolone - The same standard mixture with the addition of 40 mg of methylprednisolone.
- Standard PAI + Zilretta - The same standard mixture with 32 mg of Zilretta, the extended-release steroid.
People with diabetes or prediabetes will only be placed in groups 1 or 3 so researchers can compare how Zilretta affects them compared to no steroid at all.
What Will Be Measured
The researchers will check patients' progress at several points after surgery to investigate:
- Pain levels
- Opioid pain medication use (measured in morphine-equivalent doses)
- Knee movement (range of motion)
- Need for further procedures (such as manipulation under anesthesia, or MUA, if the knee becomes too stiff)
- Patient-reported outcome surveys (including the Knee Injury and Osteoarthritis Outcome Score and the Single Assessment Numeric Evaluation) Expected Findings
The team believes that adding a corticosteroid to the PAI will:
- Improve pain control
- Reduce the need for opioid medications
- Lower the risk of needing a manipulation procedure to improve range of motion They also expect that Zilretta, because it lasts longer, will work better than methylprednisolone-especially in people with diabetes, by offering pain relief without causing as much temporary increase in blood sugar.
Why This Matters Past research shows that PAIs can help reduce pain and the need for opioids after knee replacement surgery, without raising the risk of infection or other serious complications. But doctors still don't know which steroid is best to use. If Zilretta works better and causes fewer side effects, it could become the preferred option for many patients-particularly those with other health issues like diabetes.
The results of this study could help guide surgeons toward the safest and most effective pain control strategies for people recovering from knee replacement surgery, ultimately leading to better recoveries, fewer complications, and improved quality of life.
- Conditions
- Knee Osteoarthritis, Musculoskeletal Disease, Surgery
- Being tested
- PAI, PAI + steroid, PAI + zilretta
- Keywords
- total knee arthroplasty (TKA), manipulation under anesthesia (MUA), corticosteroid, periarticular injection/pericapsular injection (PAI), zilretta
- Medical subject headings
- Osteoarthritis, Knee, Musculoskeletal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PAIDrug
Standard PAI: 30 mg Toradol/ketorolac (30mg/ml), 49.25ml 0.5% ropivacaine (5mg/ml), and 0.5 mg
PAI + steroidDrug
Also called PAI + methylprednisolone
Standard PAI + 40mg methylprednisolone (n = 40)
PAI + zilrettaDrug
Standard PAI + 32mg Zilretta (triamcinolone acetonide extended release injectable suspension)
| Study group | Role | What they receive |
|---|---|---|
| Standard PAI | Active comparator | Group1 (n=80; 40 non-diabetic and 40 diabetic participants): Standard PAI: 30 mg Toradol/ketorolac (30mg/ml), 49.25ml 0.5% ropivacaine (5mg/ml), and 0.5 mg epinephrine (1mg/ml), 0.8 ml clonidine (0.1mg/ml) and 8.45 ml 0.9% sodium chloride Receives: Drug: PAI |
| Methylprednisolone | Active comparator | 2. Group2 (n=40, non-diabetic): Standard PAI + 40mg methylprednisolone (n = 40) Receives: Drug: PAI + steroid |
| Zilretta | Active comparator | 3. Group3 (n=80; 40 non-diabetic and 40 diabetic participants): Standard PAI + 32mg Zilretta (triamcinolone acetonide extended release injectable suspension) Receives: Drug: PAI + zilretta |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome is to determine whether total knee arthroplasty outcomes are significantly better for Zilretta (Group 3) and methylprednisolone (Group 2) as compared to standard PAI (Group 1) and Zilretta versus methylprednisolone.
The following outcomes after total knee arthroplasty will be compared to determine whether outcomes are significantly better for Zilretta (Group 3) and methylprednisolone (Group 2) as compared to standard PAI (Group 1) and Zilretta versus methylprednisolone:
- Improvement in pain levels postoperatively based on measurement of pain intensity using a Visual Analogue Scale (VAS) at 24hrs, 72 hours, and 7 days (all phone call), and 28 days
Measured: 24 hours, 72 hours, 7 days, and 28 days post
Postoperative ROM
The following outcomes after total knee arthroplasty will be compared to determine whether outcomes are significantly better for Zilretta (Group 3) and methylprednisolone (Group 2) as compared to standard PAI (Group 1) and Zilretta versus methylprednisolone: Change in range of motion (ROM) at 28, 120 and 365 days postop
Measured: 28, 120 and 365 days postop
Patient reported outcome measure
The following outcomes after total knee arthroplasty will be compared to determine whether outcomes are significantly better for Zilretta (Group 3) and methylprednisolone (Group 2) as compared to standard PAI (Group 1) and Zilretta versus methylprednisolone:
- Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) score at 120 and 365 days postoperatively
Measured: 120 and 365 days postoperatively
Patient reported outcome measures 2
The following outcomes after total knee arthroplasty will be compared to determine whether outcomes are significantly better for Zilretta (Group 3) and methylprednisolone (Group 2) as compared to standard PAI (Group 1) and Zilretta versus methylprednisolone:
- Change in Single Assessment Numeric Evaluation (SANE) score at 120 and 365 days postop
Measured: 120 and 365 days postop
Postop pain medication usage
The following outcomes after total knee arthroplasty will be compared to determine whether outcomes are significantly better for Zilretta (Group 3) and methylprednisolone (Group 2) as compared to standard PAI (Group 1) and Zilretta versus methylprednisolone:
- Decreased morphine equivalent (MEQ) postoperatively at 24hrs, 72 hours, and 7 days (all phone call), and 28 days
Measured: 24hrs, 72 hours, and 7 days, and 28 days postop
MUA rate
The following outcome after total knee arthroplasty will be compared to determine whether outcomes are significantly better for Zilretta (Group 3) and methylprednisolone (Group 2) as compared to standard PAI (Group 1) and Zilretta versus methylprednisolone:
- Decreased manipulation under anesthesia rates (MUA) compared to historical rate at our institution at 28 days
Measured: 28 days postop
Secondary outcomes (1)
Adverse events and subgroup analysis
To determine whether the adverse event rates associated with Zilretta and methylprednisolone are significantly less than the adverse event rates for standard PAI.
Measured: 28 days, 120 days, 365 days postop
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2025
- Study start1 Sep 2026 (estimated)
- Primary completion31 Aug 2027 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Knee OsteoarthritisStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Walter Reed National Military Medical Center
- Sponsor type
- US federal agency
- Responsible party
- Principal investigator, Ian P. Marshall, Walter Reed National Military Medical Center
- Investigators
- John P Cody, MD, Principal investigator, Walter Reed National Military Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07151417
- Sponsor's protocol ID
- 25-21385
- Acronym
- TKACSI
- Status last verified
- Aug 2025
- First submitted
- 13 Aug 2025
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Su C, Liu Y, Wu P, Lang J, Chen L. Comparison Between Periarticular Analgesia Versus Intraarticular Injection for Effectiveness and Safety After Total Knee Arthroplasty. J Perianesth Nurs. 2022 Dec;37(6):952-955. doi: 10.1016/j.jopan.2022.04.010. Epub 2022 Sep 16.
PubMed 36123240Hannon CP, Fillingham YA, Spangehl MJ, Karas V, Kamath AF, Casambre FD, Verity TJ, Nelson N, Hamilton WG, Della Valle CJ. The Efficacy and Safety of Periarticular Injection in Total Joint Arthroplasty: A Direct Meta-Analysis. J Arthroplasty. 2022 Oct;37(10):1928-1938.e9. doi: 10.1016/j.arth.2022.03.045.
PubMed 36162925Wang Y, Li Z, Gao X, Lin J. The efficacy and safety of intra-articular injection of corticosteroids in multimodal analgesic cocktails in total knee arthroplasty-a historically controlled study. Front Surg. 2024 Jun 11;11:1279462. doi: 10.3389/fsurg.2024.1279462. eCollection 2024.
PubMed 38919978Wainwright JD, Gugala Z, Krueger CA, Wenke JC. Adding corticosteroids to intra-operative periarticular injections in total knee arthroplasty: A systematic review. Knee. 2024 Aug;49:87-96. doi: 10.1016/j.knee.2024.05.009. Epub 2024 Jun 13.
PubMed 38876084Wainwright JD, Alaraj S, Wenke JC. Systematic review of intraoperative corticosteroid injections and the risk of infection in arthroscopic surgery. J Clin Orthop Trauma. 2024 Jan 3;48:102332. doi: 10.1016/j.jcot.2024.102332. eCollection 2024 Jan.
PubMed 38282804Sreedharan Nair V, Ganeshan Radhamony N, Rajendra R, Mishra R. Effectiveness of intraoperative periarticular cocktail injection for pain control and knee motion recovery after total knee replacement. Arthroplast Today. 2019 Jul 12;5(3):320-324. doi: 10.1016/j.artd.2019.05.004. eCollection 2019 Sep.
PubMed 31516975Schwartz A, Cochrane NH, Jiranek WA, Ryan SP. Periarticular Injection in Total Knee Arthroplasty. J Am Acad Orthop Surg. 2023 Jun 15;31(12):614-619. doi: 10.5435/JAAOS-D-22-01179. Epub 2023 Apr 14.
PubMed 37071876Russell SJ, Sala R, Conaghan PG, Habib G, Vo Q, Manning R, Kivitz A, Davis Y, Lufkin J, Johnson JR, Kelley S, Bodick N. Triamcinolone acetonide extended-release in patients with osteoarthritis and type 2 diabetes: a randomized, phase 2 study. Rheumatology (Oxford). 2018 Dec 1;57(12):2235-2241. doi: 10.1093/rheumatology/key265.
PubMed 30203101Oshima A, Hatayama K, Terauchi M, Kakiage H, Hashimoto S, Chikuda H. The comparison of dexamethasone and triamcinolone periarticular administration in total knee arthroplasty: retrospective cohort study. BMC Musculoskelet Disord. 2022 Feb 5;23(1):120. doi: 10.1186/s12891-022-05048-8.
PubMed 35123474Moon HK, Han CD, Yang IH, Cha BS. Factors affecting outcome after total knee arthroplasty in patients with diabetes mellitus. Yonsei Med J. 2008 Feb 29;49(1):129-37. doi: 10.3349/ymj.2008.49.1.129.
PubMed 18306479Liu M, Zhang D, Shi B. Comparison of the Post-Total Knee Arthroplasty Analgesic Effect of Intraoperative Periarticular Injection of Different Analgesics. J Coll Physicians Surg Pak. 2019 Dec;29(12):1169-1172. doi: 10.29271/jcpsp.2019.12.1169.
PubMed 31839089Li Q, Mu G, Liu X, Chen M. Efficacy of additional corticosteroids to multimodal cocktail periarticular injection in total knee arthroplasty: a meta-analysis of randomized controlled trials. J Orthop Surg Res. 2021 Jan 22;16(1):77. doi: 10.1186/s13018-020-02144-0.
PubMed 33482865Kulkarni M, Mallesh M, Wakankar H, Prajapati R, Pandit H. Effect of Methylprednisolone in Periarticular Infiltration for Primary Total Knee Arthroplasty on Pain and Rehabilitation. J Arthroplasty. 2019 Aug;34(8):1646-1649. doi: 10.1016/j.arth.2019.04.060. Epub 2019 May 2.
PubMed 31155459Kim JI, Kim YT, Jung HJ, Lee JK. Does adding corticosteroids to periarticular injection affect the postoperative acute phase response after total knee arthroplasty? Knee. 2020 Mar;27(2):493-499. doi: 10.1016/j.knee.2019.10.029. Epub 2019 Dec 2.
PubMed 31806506Kim DH, Beathe JC, Lin Y, YaDeau JT, Maalouf DB, Goytizolo E, Garnett C, Ranawat AS, Su EP, Mayman DJ, Memtsoudis SG. Addition of Infiltration Between the Popliteal Artery and the Capsule of the Posterior Knee and Adductor Canal Block to Periarticular Injection Enhances Postoperative Pain Control in Total Knee Arthroplasty: A Randomized Controlled Trial. Anesth Analg. 2019 Aug;129(2):526-535. doi: 10.1213/ANE.0000000000003794.
PubMed 30234517
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjunctive Use of Corticosteroid in Periarticular Injections in Primary Total Knee Arthroplasty
- ClinicalTrials.gov ID
- NCT07151417
- Acronym / sponsor ID
- TKACSI / 25-21385
- Conditions
- Knee Osteoarthritis, Musculoskeletal Disease, Surgery
- Keywords
- total knee arthroplasty (TKA), manipulation under anesthesia (MUA), corticosteroid, periarticular injection/pericapsular injection (PAI), zilretta
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Walter Reed National Military Medical CenterUS federal agency
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 31 Aug 2027 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 3 Sep 2025 (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 goal of this clinical trial is to find out which type of steroid medicine, when added to a standard pain-control injection during total knee replacement surgery, works best at reducing pain, limiting opioid use, and improving recovery in adults undergoing surgery for severe knee arthritis or injury.
The main questions it aims to answer are:
Does adding a steroid to the injection improve pain control and reduce opioid use after surgery? Is the newer extended-release steroid (Zilretta) more effective and safer-especially for patients with diabetes-than the traditional steroid (methylprednisolone)?
Researchers will compare:
Standard pain-control injection alone Standard injection plus methylprednisolone Standard injection plus Zilretta to see which option provides better pain relief, less opioid use, and improved knee function.
(Patients with diabetes or prediabetes will only be in the standard injection or Zilretta groups so researchers can study whether Zilretta is safer for blood sugar control.)
Participants will:
Be randomly assigned to one of the study groups during their total knee replacement surgery Receive the assigned pain-control injection around the knee joint
Be followed after surgery to measure:
Pain levels Opioid pain medication use Knee movement (range of motion) Whether another procedure (such as manipulation under anesthesia) is needed if the knee becomes too stiff Patient-reported outcome surveys about pain and function
Detailed description
Total knee replacement surgery (also called total knee arthroplasty, or TKA) is a common procedure for people with severe knee arthritis or injury. While the surgery often leads to significant pain relief and improved mobility, the days and weeks afterward can be uncomfortable. Managing pain during recovery is important-not just to make patients feel better, but also to help them move their knee sooner, avoid excessive use of opioid medications, and get back to normal activities faster.
One common pain management tool is called a pericapsular injection (PAI). This is a mixture of medications injected around the knee joint during surgery to help control pain after the operation. PAIs usually include a long-lasting numbing medicine, an anti-inflammatory drug, and sometimes other medications that improve pain relief. Corticosteroids-powerful anti-inflammatory drugs-are sometimes added, but the best type of steroid and the ideal way to give it is still debated among doctors.
Why This Study Is Being Done This study will compare two types of corticosteroids, methylprednisolone (a traditional steroid) and Zilretta (a newer, extended-release form of the steroid triamcinolone), to see which works better when added to the standard PAI. Zilretta releases medication slowly over time, which may lead to longer-lasting pain control and fewer side effects such as temporary increases in blood sugar-something especially important for people with diabetes.
How the Study Works
Patients having total knee replacement will be randomly placed into one of three groups:
- Standard PAI only - This mixture includes a long-acting numbing medicine, an anti-inflammatory (ketorolac), a small dose of adrenaline (epinephrine), clonidine (to help with pain control), and sterile saline.
- Standard PAI + methylprednisolone - The same standard mixture with the addition of 40 mg of methylprednisolone.
- Standard PAI + Zilretta - The same standard mixture with 32 mg of Zilretta, the extended-release steroid.
People with diabetes or prediabetes will only be placed in groups 1 or 3 so researchers can compare how Zilretta affects them compared to no steroid at all.
What Will Be Measured
The researchers will check patients' progress at several points after surgery to investigate:
- Pain levels
- Opioid pain medication use (measured in morphine-equivalent doses)
- Knee movement (range of motion)
- Need for further procedures (such as manipulation under anesthesia, or MUA, if the knee becomes too stiff)
- Patient-reported outcome surveys (including the Knee Injury and Osteoarthritis Outcome Score and the Single Assessment Numeric Evaluation) Expected Findings
The team believes that adding a corticosteroid to the PAI will:
- Improve pain control
- Reduce the need for opioid medications
- Lower the risk of needing a manipulation procedure to improve range of motion They also expect that Zilretta, because it lasts longer, will work better than methylprednisolone-especially in people with diabetes, by offering pain relief without causing as much temporary increase in blood sugar.
Why This Matters Past research shows that PAIs can help reduce pain and the need for opioids after knee replacement surgery, without raising the risk of infection or other serious complications. But doctors still don't know which steroid is best to use. If Zilretta works better and causes fewer side effects, it could become the preferred option for many patients-particularly those with other health issues like diabetes.
The results of this study could help guide surgeons toward the safest and most effective pain control strategies for people recovering from knee replacement surgery, ultimately leading to better recoveries, fewer complications, and improved quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Standard PAI | Active comparator | Drug: PAIGroup1 (n=80; 40 non-diabetic and 40 diabetic participants): Standard PAI: 30 mg Toradol/ketorolac (30mg/ml), 49.25ml 0.5% ropivacaine (5mg/ml), and 0.5 mg epinephrine (1mg/ml), 0.8 ml clonidine (0.1mg/ml) and 8.45 ml 0.9% sodium chloride |
| Methylprednisolone | Active comparator | Drug: PAI + steroid2. Group2 (n=40, non-diabetic): Standard PAI + 40mg methylprednisolone (n = 40) |
| Zilretta | Active comparator | Drug: PAI + zilretta3. Group3 (n=80; 40 non-diabetic and 40 diabetic participants): Standard PAI + 32mg Zilretta (triamcinolone acetonide extended release injectable suspension) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients within the MHS who are DEERS eligible undergoing primary TKA at Walter Reed National Military Medical Center (WRNMMC), Surgery Center of Chevy Chase or District Surgery Center
- Age 18 or older
- successful surgical intervention
Key exclusion criteria (5 listed)
- Unicompartmental knee arthroplasty (UKA)
- Revision total knee arthroplasty (rTKA)
- Females who are pregnant or nursing
- Allergic to ingredients in PAI or previous adverse reaction to steroids being used in this study
- Diabetics will be excluded from Group 2 (standard PAI + methylprednisolone)
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 |
|---|---|---|
| PAIStandard PAI: 30 mg Toradol/ketorolac (30mg/ml), 49.25ml 0.5% ropivacaine (5mg/ml), and 0.5 mg | Drug | Standard PAI |
| PAI + steroidAlso: PAI + methylprednisoloneStandard PAI + 40mg methylprednisolone (n = 40) | Drug | Methylprednisolone |
| PAI + zilrettaStandard PAI + 32mg Zilretta (triamcinolone acetonide extended release injectable suspension) | Drug | Zilretta |
Primary outcome
The primary outcome is to determine whether total knee arthroplasty outcomes are significantly better for Zilretta (Group 3) and methylprednisolone (Group 2) as compared to standard PAI (Group 1) and Zilretta versus methylprednisolone.
Time frame: 24 hours, 72 hours, 7 days, and 28 days post
The following outcomes after total knee arthroplasty will be compared to determine whether outcomes are significantly better for Zilretta (Group 3) and methylprednisolone (Group 2) as compared to standard PAI (Group 1) and Zilretta versus methylprednisolone: • Improvement in pain levels postoperatively based on measurement of pain intensity using a Visual Analogue Scale (VAS) at 24hrs, 72 hours, and 7 days (all phone call), and 28 days
Postoperative ROM
Time frame: 28, 120 and 365 days postop
The following outcomes after total knee arthroplasty will be compared to determine whether outcomes are significantly better for Zilretta (Group 3) and methylprednisolone (Group 2) as compared to standard PAI (Group 1) and Zilretta versus methylprednisolone: Change in range of motion (ROM) at 28, 120 and 365 days postop
Patient reported outcome measure
Time frame: 120 and 365 days postoperatively
The following outcomes after total knee arthroplasty will be compared to determine whether outcomes are significantly better for Zilretta (Group 3) and methylprednisolone (Group 2) as compared to standard PAI (Group 1) and Zilretta versus methylprednisolone: • Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) score at 120 and 365 days postoperatively
Patient reported outcome measures 2
Time frame: 120 and 365 days postop
The following outcomes after total knee arthroplasty will be compared to determine whether outcomes are significantly better for Zilretta (Group 3) and methylprednisolone (Group 2) as compared to standard PAI (Group 1) and Zilretta versus methylprednisolone: • Change in Single Assessment Numeric Evaluation (SANE) score at 120 and 365 days postop
Postop pain medication usage
Time frame: 24hrs, 72 hours, and 7 days, and 28 days postop
The following outcomes after total knee arthroplasty will be compared to determine whether outcomes are significantly better for Zilretta (Group 3) and methylprednisolone (Group 2) as compared to standard PAI (Group 1) and Zilretta versus methylprednisolone: • Decreased morphine equivalent (MEQ) postoperatively at 24hrs, 72 hours, and 7 days (all phone call), and 28 days
MUA rate
Time frame: 28 days postop
The following outcome after total knee arthroplasty will be compared to determine whether outcomes are significantly better for Zilretta (Group 3) and methylprednisolone (Group 2) as compared to standard PAI (Group 1) and Zilretta versus methylprednisolone: • Decreased manipulation under anesthesia rates (MUA) compared to historical rate at our institution at 28 days
1 secondary outcome
Adverse events and subgroup analysis
Time frame: 28 days, 120 days, 365 days postop
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 19 Aug 2026.
- Background: PubMed 36123240Su C, Liu Y, Wu P, Lang J, Chen L. Comparison Between Periarticular Analgesia Versus Intraarticular Injection for Effectiveness and Safety After Total Knee Arthroplasty. J Perianesth Nurs. 2022 Dec;37(6):952-955. doi: 10.1016/j.jopan.2022.04.010. Epub 2022 Sep 16.
- Background: PubMed 36162925Hannon CP, Fillingham YA, Spangehl MJ, Karas V, Kamath AF, Casambre FD, Verity TJ, Nelson N, Hamilton WG, Della Valle CJ. The Efficacy and Safety of Periarticular Injection in Total Joint Arthroplasty: A Direct Meta-Analysis. J Arthroplasty. 2022 Oct;37(10):1928-1938.e9. doi: 10.1016/j.arth.2022.03.045.
- Results publication: PubMed 38919978Wang Y, Li Z, Gao X, Lin J. The efficacy and safety of intra-articular injection of corticosteroids in multimodal analgesic cocktails in total knee arthroplasty-a historically controlled study. Front Surg. 2024 Jun 11;11:1279462. doi: 10.3389/fsurg.2024.1279462. eCollection 2024.
- Results publication: PubMed 38876084Wainwright JD, Gugala Z, Krueger CA, Wenke JC. Adding corticosteroids to intra-operative periarticular injections in total knee arthroplasty: A systematic review. Knee. 2024 Aug;49:87-96. doi: 10.1016/j.knee.2024.05.009. Epub 2024 Jun 13.
- Results publication: PubMed 38282804Wainwright JD, Alaraj S, Wenke JC. Systematic review of intraoperative corticosteroid injections and the risk of infection in arthroscopic surgery. J Clin Orthop Trauma. 2024 Jan 3;48:102332. doi: 10.1016/j.jcot.2024.102332. eCollection 2024 Jan.
- Results publication: PubMed 31516975Sreedharan Nair V, Ganeshan Radhamony N, Rajendra R, Mishra R. Effectiveness of intraoperative periarticular cocktail injection for pain control and knee motion recovery after total knee replacement. Arthroplast Today. 2019 Jul 12;5(3):320-324. doi: 10.1016/j.artd.2019.05.004. eCollection 2019 Sep.
- Results publication: PubMed 37071876Schwartz A, Cochrane NH, Jiranek WA, Ryan SP. Periarticular Injection in Total Knee Arthroplasty. J Am Acad Orthop Surg. 2023 Jun 15;31(12):614-619. doi: 10.5435/JAAOS-D-22-01179. Epub 2023 Apr 14.
- Results publication: PubMed 30203101Russell SJ, Sala R, Conaghan PG, Habib G, Vo Q, Manning R, Kivitz A, Davis Y, Lufkin J, Johnson JR, Kelley S, Bodick N. Triamcinolone acetonide extended-release in patients with osteoarthritis and type 2 diabetes: a randomized, phase 2 study. Rheumatology (Oxford). 2018 Dec 1;57(12):2235-2241. doi: 10.1093/rheumatology/key265.
- Results publication: PubMed 35123474Oshima A, Hatayama K, Terauchi M, Kakiage H, Hashimoto S, Chikuda H. The comparison of dexamethasone and triamcinolone periarticular administration in total knee arthroplasty: retrospective cohort study. BMC Musculoskelet Disord. 2022 Feb 5;23(1):120. doi: 10.1186/s12891-022-05048-8.
- Results publication: PubMed 18306479Moon HK, Han CD, Yang IH, Cha BS. Factors affecting outcome after total knee arthroplasty in patients with diabetes mellitus. Yonsei Med J. 2008 Feb 29;49(1):129-37. doi: 10.3349/ymj.2008.49.1.129.
- Results publication: PubMed 31839089Liu M, Zhang D, Shi B. Comparison of the Post-Total Knee Arthroplasty Analgesic Effect of Intraoperative Periarticular Injection of Different Analgesics. J Coll Physicians Surg Pak. 2019 Dec;29(12):1169-1172. doi: 10.29271/jcpsp.2019.12.1169.
- Results publication: PubMed 33482865Li Q, Mu G, Liu X, Chen M. Efficacy of additional corticosteroids to multimodal cocktail periarticular injection in total knee arthroplasty: a meta-analysis of randomized controlled trials. J Orthop Surg Res. 2021 Jan 22;16(1):77. doi: 10.1186/s13018-020-02144-0.
- 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.
John P Cody, MD principal investigator
Walter Reed National Military Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing PAI, PAI + steroid and PAI + zilretta in people with Knee Osteoarthritis and Musculoskeletal Disease, run by Walter Reed National Military Medical Center 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 5 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 19 Aug 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 John P Cody, MD (301-538-2472, john.p.cody3.mil@health.mil), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome is to determine whether total knee arthroplasty outcomes are significantly better for Zilretta (Group 3) and methylprednisolone (Group 2) as compared to standard PAI (Group 1) and Zilretta versus methylprednisolone. (time frame: 24 hours, 72 hours, 7 days, and 28 days post). The study lists 6 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 NCT07151417, which also lists 16 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 19 Aug 2026.