Medrol Dosepak for Total Knee Replacement

Overseen By tad gerlinger, md

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Rush University Medical Center

Must not be taking: Corticosteroids, Opiates

Disqualifiers: Infection, Diabetes, Heart failure, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 week

420 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether methylprednisolone, a corticosteroid, can reduce pain, the need for opioids, nausea, and complications after total knee replacement due to osteoarthritis. Participants will begin taking the medication or a placebo (a sugar pill resembling the medication) the day after surgery. The trial aims to determine if methylprednisolone improves recovery within the first week and aids pain and movement up to six weeks post-surgery. Individuals with osteoarthritis planning their first knee replacement may be suitable for this trial. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment benefits more patients.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, if you are using chronic corticosteroids or opiates, you cannot participate in the trial.

What is the safety track record for methylprednisolone?

Research has shown that methylprednisolone is generally well-tolerated by people undergoing total knee replacement surgery. Studies have found that it can significantly reduce pain and decrease the need for opioids post-surgery, potentially leading to fewer opioid-related side effects, such as nausea.

In another study, patients who received corticosteroids, including methylprednisolone, experienced less pain and nausea after joint surgery. However, the risk of infection slightly increased, with 1.9% of patients experiencing infection compared to 1.1% of those who did not receive the corticosteroid.

Overall, methylprednisolone appears safe for most patients, with the benefits of less pain and reduced opioid use outweighing the small risk of infection. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard approach to managing post-operative inflammation and pain after total knee replacement, which often involves nonsteroidal anti-inflammatory drugs (NSAIDs) or opioids, the Methylprednisolone taper uses a corticosteroid known for its powerful anti-inflammatory properties. Methylprednisolone acts by reducing inflammation through immune system modulation, which can potentially lead to faster recovery times and improved mobility. Researchers are excited about this treatment because it provides a targeted approach to minimizing inflammation without the side effects associated with long-term NSAID or opioid use. This could mean a safer recovery process with less reliance on medications that carry higher risks of dependency or gastrointestinal issues.

What evidence suggests that Medrol Dosepak might be an effective treatment for postoperative pain and function after total knee replacement?

Research has shown that methylprednisolone, which participants in this trial may receive, can reduce pain and the need for strong painkillers after a total knee replacement. One study found it significantly lowered pain levels post-surgery and reduced opioid use. This suggests patients might experience less pain and fewer side effects from these medications. Another study demonstrated that methylprednisolone improved knee movement and function after surgery. These findings suggest that methylprednisolone effectively manages pain and enhances knee movement following a knee replacement. Participants in this trial will be randomized to receive either a methylprednisolone taper or a placebo taper. ^{3 6 7 8 9}

Who Is on the Research Team?

Craig Della Valle, MD

Principal Investigator

Rush University Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 undergoing their first total knee replacement due to osteoarthritis. Participants must be willing to be randomly assigned a treatment and able to take oral medication. It's not for those with certain chronic diseases, immune system issues, or infections; pregnant women; or anyone unable to consent.

Inclusion Criteria

I am having a knee replacement due to osteoarthritis.

Willingness to undergo randomization

Exclusion Criteria

My immune system is weak due to a condition or medication.

I am unable to give my consent.

I cannot take medications by mouth.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a methylprednisolone taper or placebo starting on postoperative day 1 following total knee arthroplasty

1 week

Daily monitoring (virtual or in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 3 and 6 weeks postoperatively

6 weeks

2 visits (in-person) at 3 and 6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Methylprednisolone
• Placebo

Trial Overview The study tests if an oral steroid called methylprednisolone can reduce pain, improve function, lessen opioid use and nausea after knee surgery compared to a placebo. The effects are measured from the day after surgery up to six weeks postoperatively.

How Is the Trial Designed?

Group I: Methylprednisolone taper Experimental Treatment 1 Intervention

Methylprednisolone taper - 21 x 4mg tablets beginning on POD 1

Group II: Placebo taper Placebo Group 1 Intervention

2.Placebo taper - 21 sugar tablets beginning on POD 1 with standard management

Methylprednisolone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Approved in European Union as Depo-Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Approved in Canada as Solu-Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Who Is Running the Clinical Trial?

Rush University Medical Center

Lead Sponsor

Trials

448

Recruited

247,000+

Published Research Related to This Trial

In a study of 24 adult patients with rheumatoid arthritis, treatment with osmic acid combined with hydrocortisone acetate resulted in less joint swelling (hydrops) after 6 months compared to treatment with methylprednisolone acetate alone.

Patients receiving osmic acid experienced greater pain relief than those treated with corticosteroids, suggesting that osmic acid may be a more effective option for managing symptoms in RA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osmic acid in rheumatoid synovitis. A controlled study. Nissilä, M., Isomäki, H., Koota, K., et al.[2019]

Intramedullary injection of methylprednisolone acetate (Depo-Medrol) effectively treats unicameral cysts in children, as demonstrated in a rabbit model where the drug was injected into the tibia.

The study found that while serum levels of methylprednisolone rose quickly, indicating systemic absorption, there were no significant local histological changes such as fibroblastic proliferation or neovascularization, suggesting that the mechanism of action may not involve direct tissue alteration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The systemic and local effects of an intramedullary injection of methylprednisolone acetate in growing rabbits. Colville, MR., Aronson, DD., Prcevski, P., et al.[2019]

The study found that the new high-dose (100 mg) methylprednisolone tablet has an absolute bioavailability of 82%, indicating it is effectively absorbed in the body when taken orally.

No adverse drug reactions were reported, and the tablet can safely substitute for intravenous methylprednisolone in high-dose therapy, as it produced expected changes in blood neutrophil counts without significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absolute bioavailability of a new high dose methylprednisolone tablet formulation. Groenewoud, G., Hundt, HK., Luus, HG., et al.[2013]

A four-year-old girl experienced serious complications, including retinal tear and detachment, after an accidental intraocular injection of methylprednisolone acetate during a biopsy for an orbital hemangioma.

Surgical interventions, including lensectomy and vitrectomy, were successfully employed to restore visual function and prevent further damage from the corticosteroid's toxic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iatrogenic intraocular injection of depot corticosteroid and its surgical removal using the pars plana approach. Zinn, KM.[2019]

Inadvertent injection of methylprednisolone acetate into the eye during vitrectomy can lead to severe retinal toxicity, resulting in significant vision loss and complications such as retinal necrosis and optic nerve damage.

This case highlights the critical need for careful identification of medications during eye surgeries to prevent serious adverse effects associated with incorrect injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal necrosis secondary to inadvertent intravitreal methylprednisolone acetate (depo-medrol) injection during pars plana vitrectomy. Yonekawa, Y., Sun, G., D'Amico, DJ., et al.[2014]

A survey of sports medicine physicians revealed that 47% prescribe methylprednisolone taper (Medrol Dosepak) for sports injuries, particularly in patients aged 40 and younger, with postinjury disease being the most common reason for its use.

Concerns about complications, especially the risk of osteonecrosis (reported in 8.5% of prescribers), and a lack of proven efficacy were significant reasons for the 52% of physicians who chose not to prescribe Medrol Dosepak.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey of orthopaedic and sports medicine physicians regarding use of medrol dosepak for sports injuries. Langer, P., Fadale, P., Hulstyn, M., et al.[2018]

Methylprednisolone acetate (Depo-Medrol) injections via epidural or intrathecal routes can effectively relieve diskogenic back pain and radiculopathy when conservative treatments have failed, particularly if symptoms have lasted less than three months.

Corticosteroid injections are less effective for patients with chronic symptoms lasting over three months or those who have previously undergone surgery, suggesting a limited window for optimal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of diskogenic pain using epidural and intrathecal steroids. Brown, FW.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30120990/

The efficacy and safety of methylprednisolone for pain ... Methylprednisolone could significantly decrease postoperative pain score, narcotic consumption and opioid-related adverse effects after TKA.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05859269

Methylprednisolone Taper After Total Knee Replacement The study aims to evaluate the efficacy of a post-operative course of glucocorticoids on pain, range of motion, and extremity function after total knee ...

3. arthroplastytoday.org arthroplastytoday.org/article/S2352-3441(24)00288-7/fulltext

Administration of a Methylprednisolone Taper and ... This study provides preliminary evidence regarding the safety profile of a short duration of postoperative oral corticosteroids following TKA.

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05859269/methylprednisolone-taper-after-total-knee-replacement

Methylprednisolone Taper After Total Knee Replacement The study aims to evaluate the efficacy of a post-operative course of glucocorticoids on pain, range of motion, and extremity function after total knee ...

5. jbjs.org jbjs.org/reader.php?rsuite_id=8ec5fdb8-0da9-45e0-b7ee-3843fb352db6

Pain Relief After Total Knee Arthroplasty with Intravenous ... The role of IVS in pain management after TKA has been confirmed in meta-analyses, which showed a significant reduction in postoperative pain and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11930429/

Administration of a Methylprednisolone Taper and ... Most patients undergoing total knee arthroplasty (TKA) report moderate to severe pain in the acute postoperative period. Recent preliminary data have ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1743919118315450

The efficacy and safety of methylprednisolone for pain ... Methylprednisolone could significantly decrease postoperative pain score, narcotic consumption and opioid-related adverse effects after TKA.

8. arthroplastyjournal.org arthroplastyjournal.org/article/S0883-5403(22)00386-2/abstract

The Efficacy and Safety of Corticosteroids in Total Joint ... Corticosteroids are commonly used intraoperatively to treat pain and reduce opioid consumption and nausea associated with primary total joint arthroplasty ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8681887/

Intra-Articular Corticosteroid Injection After Total Knee ... The results indicated that within six months after IASI into a TKR, 1.9% of TKRs became infected (107 patients) versus 1.1% in the control group ...