A Phase 2/3 interventional study of PAI and PAI + steroid in Knee Osteoarthritis, Musculoskeletal Disease and Surgery, sponsored by Walter Reed National Military Medical Center. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-19.
Sponsored by Walter Reed National Military Medical Center · Phase 2/3, Interventional, and Treatment
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
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:
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:
The team believes that adding a corticosteroid to the PAI will:
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.
3,292 studies on the registry are indexed under Osteoarthritis, Knee; 623 are open to participants now.
This study's planned enrollment of 240 is above the median of 68 across 2,714 interventional studies indexed under Osteoarthritis, Knee.
Browse Osteoarthritis, Knee studies →Walter Reed National Military Medical Center is the lead sponsor of 78 studies on the registry; 20 are open to participants now.
Of its 10 completed or terminated interventional studies of FDA-regulated products, 3 (30%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
2\. Group2 (n=40, non-diabetic): Standard PAI + 40mg methylprednisolone (n = 40)
Drug: PAI + steroid
3\. Group3 (n=80; 40 non-diabetic and 40 diabetic participants): Standard PAI + 32mg Zilretta (triamcinolone acetonide extended release injectable suspension)
Drug: PAI + zilretta
Standard PAI: 30 mg Toradol/ketorolac (30mg/ml), 49.25ml 0.5% ropivacaine (5mg/ml), and 0.5 mg
Drug page: Steroids
Standard PAI + 40mg methylprednisolone (n = 40)
Also known as: PAI + methylprednisolone
Drug page: Triamcinolone Acetonide
Standard PAI + 32mg Zilretta (triamcinolone acetonide extended release injectable suspension)
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 28 days postop
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.
Time frame: 28 days, 120 days, 365 days postop
Plan to share: No
Start is estimated for Sep 2026; primary completion for Aug 2027, 11 months later.
Of 18 phase 2/3 interventional studies under Osteoarthritis, Knee, half reached primary completion within 31 months of starting (the median), counting those still running; a quarter within 11 and three quarters within 43. This study's planned 11 months is below that.
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Studies of the drugs tested here: Steroids · Triamcinolone Acetonide
Walter Reed National Military Medical Center