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Total Knee ArthroplastyPhase 4NCT05097976

Medrol Dosepak for Outpatient Total Knee Arthroplasty

A Phase 4 study testing Methylprednisolone in people with Total Knee Arthroplasty, run by Rush University Medical Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Total Knee Arthroplasty
What is being tested?
Methylprednisolone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
420 participants
Where
1 siteUnited States
Study dates
1 Mar 2022to Dec 2027
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Any patient undergoing primary TKA with a diagnosis of osteoarthritis
  • •≥ 18 years old
  • Willingness to undergo randomization

Who cannot join

  • Reported chronic corticosteroid or opiate use
  • Suspected or confirmed periprosthetic joint infection
  • Revision TKA
  • Primary diagnosis other than osteoarthritis, including avascular necrosis, fracture, or post-traumatic arthritis
  • American Society of Anesthesiologists (ASA) score ≥ 4
  • Reported history of liver disease, renal disease, or diabetes mellitus
Show all 15Show fewer
  • Current systemic fungal infection or other local infection
  • Immunocompromised or immunosuppressed
  • Current peptic ulcer disease
  • History of hypothyroidism, psychosis, heart failure, myasthenia gravis, ocular herpes simplex virus, or systemic sclerosis
  • Women with reported current pregnancy
  • Known hypersensitivity to methylprednisolone
  • •≤ 18 years old
  • Inability to take oral medications
  • Unable to provide consent

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting
  • Rush Oak Brook Outpatient Center

    Oak Brook, Illinois, 60523

    Anne DeBenedetti, BA, 3124322468, anne.debenedetti@rushortho.com

    craig Della Valle, MD

    Recruiting

Other trials in United States

About this study

Official title: An Oral Methylprednisolone Taper Within a Multimodal Analgesic Regimen After Total Knee Arthroplasty: a Double-Blind Randomized Placebo-Controlled 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.

Read the detailed description

Total knee arthroplasty (TKA) has been associated with severe pain in the acute postoperative period. Studies have demonstrated highest pain scores on POD 1 following TKA, however over 50% of patients describe the first two weeks at home as the most painful period of recovery marked by moderate to severe pain. This is an important finding as higher levels of acute pain have been associated with chronic opioid use, disturbed sleep, and impaired early mobilization, which can prolong recovery time and increase rates of adverse events, including venous thromboembolism.

Therefore, extensive research in pain management has been conducted with the purpose of reducing acute postoperative pain. This is of particular interest because over the past two decades average length of hospital stay has decreased while rates of outpatient TKAs with same day discharge has increased. A multimodal pain regimen enables the on-boarding of several medications, including anesthesia and analgesics working at varied pathways to target pain and inflammation, and has proven to be efficacious. This not only decreases patient reported pain scores but is also associated with improved sleep and functional recovery. Despite efficacious multimodal pain regimens, including periarticular injection cocktails, rebound pain in the early postoperative period and medication-induced nausea and vomiting can be problematic.

Corticosteroids are potent anti-inflammatory and pain pathway modulators, and therefore have become an important component of multimodal pain regimens. Corticosteroids have been shown to decrease postoperative levels of inflammatory mediators, such as IL-6 and C-reactive protein. Corticosteroids also block the synthesis of prostaglandins, a nociceptive pain receptor sensitizer and inflammatory mediator that is associated with edema via increased vascular permeability.

The administration of perioperative steroids to mitigate potential impairments in postoperative TKA recovery has been studied extensively in the orthopedic literature. The addition of corticosteroids to multimodal pain regiments, including systemic corticosteroids or perioperative periarticular joint cocktails, has demonstrated improved acute postoperative pain scores function and decreased opioid use without an increase in adverse outcomes, as compared to controls.

Researchers have investigated the effect of additional doses of corticosteroids in the immediate postoperative period. Administration of IV dexamethasone 24 hours postoperatively correlated with lower acute opioid and antiemetic use, and improved pain scores, nausea, length of stay and range of motion, as compared to controls or perioperative corticosteroids alone. The addition of a second postoperative corticosteroid dose, at 24 and 48 hours, have been associated with even greater improvements in pain and function scores, without an increase in complications.

The addition of a methylprednisolone taper within a standard multimodal pain regimen in the immediate postoperative period has been evaluated in other orthopedic subspecialties. A methylprednisolone taper following lumbar laminectomy and distal radius repair demonstrated acute reductions in patient reported pain scores, without an increase in adverse events. The current literature supports these findings, demonstrating the safety of short term and low dose corticosteroid treatments, including a methylprednisolone taper.

To the best of our knowledge, no prior study has compared the administration of a methylprednisolone taper to a placebo in the immediate postoperative period following TKA. Therefore, the purpose of this double-blind randomized placebo-controlled trial is to evaluate the efficacy of a methylprednisolone taper within a standard postoperative multimodal pain regimen. The authors predict improved pain and decreased opioid use and nausea from POD 1 to POD 7, as well as improved pain, function, and complication rate at 3- and 6-weeks postoperatively.

Being tested
Methylprednisolone, Placebo
Keywords
Methylprednisolone, acute postoperative pain, acute function, opioid consumption, complications following total knee arthroplasty
Medical subject headings
Pain, Postoperative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MethylprednisoloneDrug

    Also called medrol dosepak

    21 x 4mg tablets beginning on POD 1

  • PlaceboDrug

    21 sugar tablets beginning on POD 1 with standard management

Study groups in NCT05097976
Study groupRoleWhat they receive
Methylprednisolone taperExperimentalMethylprednisolone taper - 21 x 4mg tablets beginning on POD 1
Receives: Drug: Methylprednisolone
Placebo taperPlacebo comparator2.Placebo taper - 21 sugar tablets beginning on POD 1 with standard management
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Opioid consumption at one-week postoperative

    Relative difference in cumulative opioid consumption at Post-op day 7, measured in morphine equivalents.

    Measured: one week

Secondary outcomes (12)
  1. Patient reported outcome measures: Daily Visual Analogue Scale for Pain

    Using Daily Visual Analogue Scale (VAS) pain score, scale of 1 to 10, 10 being the worst

    Measured: Week 1

  2. Patient reported outcome measures : Daily Visual Analogue Scale for Pain

    Using Daily Visual Analogue Scale (VAS) pain score, scale of 1 to 10, 10 being the worst

    Measured: 3 weeks

  3. Patient reported outcome measures: Daily Visual Analogue Scale for Pain

    Using Daily Visual Analogue Scale (VAS) pain score, scale of 1 to 10, 10 being the worst

    Measured: 6 weeks

  4. Patient reported outcome measures: Daily Visual Analogue Scale of nausea

    Daily visual analogue scale- nausea score, scale of 1 to 10, 10 being the worst

    Measured: Postoperative days 1 through 7 (week one)

  5. Patient reported outcome measures: vomiting episodes

    Number of vomiting episodes, patient reported

    Measured: Postoperative days 1 through 7 (week 1)

  6. Patient reported outcome measures: hours of sleep

    Number of hours slept- patient reported

    Measured: Postoperative days 1 through 7 (week one)

  7. Clinical outcome: range of motion

    range of motion of knee

    Measured: Preoperatively

  8. Clinical outcome: range of motion

    range of motion of knee

    Measured: 3 weeks after treatment

  9. Clinical outcome: range of motion

    range of motion of knee

    Measured: 6 weeks after treatment

  10. Patient reported outcome measures: knee society score

    Knee society score (KSS) survey

    Measured: Preoperatively

  11. Patient reported outcome measures: knee society score

    Knee society score (KSS) survey

    Measured: 3 weeks after treatment

  12. Patient reported outcome measures: knee society score

    Knee society score (KSS) survey

    Measured: 6 weeks after treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Oct 2021
  2. Study start1 Mar 2022
  3. Primary completion30 May 2027 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
420 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05097976
Sponsor's protocol ID
21090203
Status last verified
Jul 2026
First submitted
18 Oct 2021
Last updated
9 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Methylprednisolone in people with Total Knee Arthroplasty, run by Rush University Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 9 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Anne DeBenedetti (3124322468, anne.debenedetti@rushortho.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Opioid consumption at one-week postoperative (time frame: one week). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2026.

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