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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy of an oral methylprednisolone taper on acute postoperative pain, function, opioid consumption, nausea, and complications following outpatient total knee arthroplasty (TKA). We hypothesize that administration of an oral methylprednisolone taper starting on postoperative day 1 (POD 1) following TKA will be associated with improved pain and decreased opioid use, nausea, and complications at POD1-7, as compared to similar patients who receive placebo. Additionally, those taking methylprednisolone will report decreased pain and greater objective functional outcomes at 3 and 6 weeks postoperatively as compared to controls.

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 data supports the effectiveness of the drug Medrol Dosepak for total knee replacement?

Methylprednisolone, a component of Medrol Dosepak, has been used to relieve pain in conditions like diskogenic back pain and rheumatoid arthritis, suggesting it may help with inflammation and pain management after knee replacement surgery. ^{1 2 3 4 5}

Is Medrol Dosepak (Methylprednisolone) generally safe for humans?

Methylprednisolone, used in various forms like Medrol Dosepak, has been associated with complications when accidentally injected into the eye, causing retinal damage. However, when used correctly, it is generally considered safe, as studies show it is rapidly cleared from the body and does not cause significant tissue changes in controlled settings. ^{1 3 4 5 6}

How is the drug Medrol Dosepak unique for total knee replacement?

Medrol Dosepak, which contains methylprednisolone, is unique because it offers a high-dose oral corticosteroid option that can be used as a substitute for intravenous administration, providing flexibility in managing inflammation and pain after total knee replacement. ^{1 3 4 5 7}

Research Team

Craig Della Valle, MD

Principal Investigator

Rush University Medical Center

Eligibility Criteria

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.

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Retinal necrosis secondary to inadvertent intravitreal methylprednisolone acetate (depo-medrol) injection during pars plana vitrectomy. [2014]

2. England pubmed.ncbi.nlm.nih.gov

Osmic acid in rheumatoid synovitis. A controlled study. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Survey of orthopaedic and sports medicine physicians regarding use of medrol dosepak for sports injuries. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

The systemic and local effects of an intramedullary injection of methylprednisolone acetate in growing rabbits. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. Germany pubmed.ncbi.nlm.nih.gov

Absolute bioavailability of a new high dose methylprednisolone tablet formulation. [2013]