Use of Corticosteroid in Intraopertive Injections in Total Knee Replacement Surgery.

NCT07151417 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: 25-21385
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief 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. 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

Conditions

Knee Osteoarthritis; Musculoskeletal Disease; Surgery

Keywords

total knee arthroplasty (TKA); manipulation under anesthesia (MUA); corticosteroid; periarticular injection/pericapsular injection (PAI); zilretta

Outcome Measures

Primary Outcomes (6)

• 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

  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

  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

  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

  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

  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

  28 days postop

Secondary Outcomes (1)

• Adverse events and subgroup analysis

  28 days, 120 days, 365 days postop

Study Arms (3)

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

Drug: PAI

Methylprednisolone

ACTIVE COMPARATOR

2\. Group2 (n=40, non-diabetic): Standard PAI + 40mg methylprednisolone (n = 40)

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)

Drug: PAI + zilretta

Interventions

PAI DRUG

Standard PAI: 30 mg Toradol/ketorolac (30mg/ml), 49.25ml 0.5% ropivacaine (5mg/ml), and 0.5 mg

Standard PAI

PAI + steroid DRUG

Standard PAI + 40mg methylprednisolone (n = 40)

Also known as: PAI + methylprednisolone

Methylprednisolone

PAI + zilretta DRUG

Standard PAI + 32mg Zilretta (triamcinolone acetonide extended release injectable suspension)

Zilretta

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Walter Reed National Military Medical Center: lead

Study Sites (1)

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

Location

Related Publications (16)

• Wang 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.

  PMID: 38919978 BACKGROUND

• Wainwright 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.

  PMID: 38876084 BACKGROUND

• Wainwright 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.

  PMID: 38282804 BACKGROUND

• 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.

  PMID: 36123240 BACKGROUND

• Sreedharan 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.

  PMID: 31516975 BACKGROUND

• Schwartz 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.

  PMID: 37071876 BACKGROUND

• Russell 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.

  PMID: 30203101 BACKGROUND

• Oshima 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.

  PMID: 35123474 BACKGROUND

• Moon 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.

  PMID: 18306479 BACKGROUND

• Liu 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.

  PMID: 31839089 BACKGROUND

• Li 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.

  PMID: 33482865 BACKGROUND

• Kulkarni 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.

  PMID: 31155459 BACKGROUND

• Kim 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.

  PMID: 31806506 BACKGROUND

• Kim 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.

  PMID: 30234517 BACKGROUND

• Kg G, J R. Efficacy of Intraoperative Periarticular Local Infiltration for Pain Control and Ambulation in Total Knee Arthroplasty: A Randomized Case-Control Study. Cureus. 2024 Jan 20;16(1):e52639. doi: 10.7759/cureus.52639. eCollection 2024 Jan.

  PMID: 38380215 BACKGROUND

• Hannon 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.

  PMID: 36162925 BACKGROUND

MeSH Terms

Conditions

Osteoarthritis, Knee; Musculoskeletal Diseases

Interventions

Steroids; Methylprednisolone; Triamcinolone

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Fused-Ring Compounds; Polycyclic Compounds; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids, Fluorinated

Study Officials

• John P Cody, MD

  Walter Reed National Military Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John P Cody, MD

CONTACT

301-538-2472; john.p.cody3.mil@health.mil

Ian P Marshall, MD

CONTACT

585-576-7864; ian.p.marshall.mil@health.mil

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Research participants will be randomized to one of three groups unless they are diabetic or pre-diabetic then they will be randomized to one of 2 groups (Group 1 or Group 3). Participants will not know to which group they were randomized to. The groups that participants will be randomized to are: Group 1: 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 Group 2: Standard PAI + 40mg methylprednisolone (diabetics and pre-diabetics will not be randomized to this group) Group 3: Standard PAI + 32mg Zilretta (triamcinolone acetonide extended release injectable suspension)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Resident Physician, Orthopaedic Surgery

Study Record Dates

• First Submitted: August 13, 2025
• First Posted: September 3, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)