Recruiting
Phase 2
Phase 3

Zilretta & Methylprednisolone

Sponsor:

Walter Reed National Military Medical Center

Code:

NCT07151417

Conditions

Knee Osteoarthritis

Musculoskeletal Disease

Surgery

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

PAI

PAI + steroid

PAI + zilretta

Study Details

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

Study ID

NCT07151417

Start date

Sep 1, 2026

Status verified date

Aug, 2025

Completion date

Aug 31, 2027

Anticipated

Primary completion date

Aug 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)

Study Design

Enrollment

240 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Standard PAI

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

active comparator: Methylprednisolone

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

active comparator: Zilretta

3\. Group3 (n=80; 40 non-diabetic and 40 diabetic participants): Standard PAI + 32mg Zilretta (triamcinolone acetonide extended release injectable suspension)

Interventions

PAI

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

PAI + steroid

Standard PAI + 40mg methylprednisolone (n = 40)

PAI + zilretta

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

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 ]
  • Postoperative ROM [ Time Frame: 28, 120 and 365 days postop ]
  • Patient reported outcome measure [ Time Frame: 120 and 365 days postoperatively ]
  • Patient reported outcome measures 2 [ Time Frame: 120 and 365 days postop ]
  • Postop pain medication usage [ Time Frame: 24hrs, 72 hours, and 7 days, and 28 days postop ]
  • MUA rate [ Time Frame: 28 days postop ]

Central Contacts and Locations

Central contacts

John P Cody, MD

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

Ian P Marshall, MD

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

Locations

Walter Reed National Military Medical Center

Recruiting

Bethesda, Maryland, United States, 20889

Contacts

John P Cody, MD

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

Principal Investigator:

John P. Cody, MD

More Information

Sponsor

Walter Reed National Military Medical Center

Last update posted

Aug 19, 2026

Last verified

Aug, 2025

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Walter Reed National Military Medical Center on 2026-08-19.