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.
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
- Recruiting
Rush Oak Brook Outpatient Center
Oak Brook, Illinois, 60523
Anne DeBenedetti, BA, 3124322468, anne.debenedetti@rushortho.com
craig Della Valle, MD
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.
- Conditions
- Total Knee Arthroplasty
- 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.
Also called medrol dosepak
21 x 4mg tablets beginning on POD 1
PlaceboDrug
21 sugar tablets beginning on POD 1 with standard management
| Study group | Role | What they receive |
|---|---|---|
| Methylprednisolone taper | Experimental | Methylprednisolone taper - 21 x 4mg tablets beginning on POD 1 Receives: Drug: Methylprednisolone |
| Placebo taper | Placebo comparator | 2.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.
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)
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
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
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
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)
Patient reported outcome measures: vomiting episodes
Number of vomiting episodes, patient reported
Measured: Postoperative days 1 through 7 (week 1)
Patient reported outcome measures: hours of sleep
Number of hours slept- patient reported
Measured: Postoperative days 1 through 7 (week one)
Clinical outcome: range of motion
range of motion of knee
Measured: Preoperatively
Clinical outcome: range of motion
range of motion of knee
Measured: 3 weeks after treatment
Clinical outcome: range of motion
range of motion of knee
Measured: 6 weeks after treatment
Patient reported outcome measures: knee society score
Knee society score (KSS) survey
Measured: Preoperatively
Patient reported outcome measures: knee society score
Knee society score (KSS) survey
Measured: 3 weeks after treatment
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.
- First posted28 Oct 2021
- Study start1 Mar 2022
- Primary completion30 May 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Total Knee ArthroplastyStudies of the same condition, open and under way.
- More trials run by Rush University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Rush University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Craig J Della Valle, MD, Rush University Medical Center
- Investigators
- Craig Della Valle, MD, Principal investigator, Rush University Medical Center
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
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Oral Methylprednisolone Taper Within a Multimodal Analgesic Regimen After Total Knee Arthroplasty: a Double-Blind Randomized Placebo-Controlled Trial
- ClinicalTrials.gov ID
- NCT05097976
- Acronym / sponsor ID
- 21090203
- Conditions
- Total Knee Arthroplasty
- Keywords
- Methylprednisolone, acute postoperative pain, acute function, opioid consumption, complications following total knee arthroplasty
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 420 participants (estimated)
- Lead sponsor
- Rush University Medical CenterUniversity, hospital or other
- Study start
- 1 Mar 2022 (actual)
- Primary completion
- 30 May 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 28 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methylprednisolone taper | Experimental | Drug: MethylprednisoloneMethylprednisolone taper - 21 x 4mg tablets beginning on POD 1 |
| Placebo taper | Placebo comparator | Drug: Placebo2.Placebo taper - 21 sugar tablets beginning on POD 1 with standard management |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Any patient undergoing primary TKA with a diagnosis of osteoarthritis
- •≥ 18 years old
- Willingness to undergo randomization
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethylprednisoloneAlso: medrol dosepak21 x 4mg tablets beginning on POD 1 | Drug | Methylprednisolone taper |
| Placebo21 sugar tablets beginning on POD 1 with standard management | Drug | Placebo taper |
Primary outcome
Opioid consumption at one-week postoperative
Time frame: one week
Relative difference in cumulative opioid consumption at Post-op day 7, measured in morphine equivalents.
12 secondary outcomes
Patient reported outcome measures: Daily Visual Analogue Scale for Pain
Time frame: Week 1
Patient reported outcome measures : Daily Visual Analogue Scale for Pain
Time frame: 3 weeks
Patient reported outcome measures: Daily Visual Analogue Scale for Pain
Time frame: 6 weeks
Patient reported outcome measures: Daily Visual Analogue Scale of nausea
Time frame: Postoperative days 1 through 7 (week one)
Patient reported outcome measures: vomiting episodes
Time frame: Postoperative days 1 through 7 (week 1)
Patient reported outcome measures: hours of sleep
Time frame: Postoperative days 1 through 7 (week one)
Clinical outcome: range of motion
Time frame: Preoperatively
Clinical outcome: range of motion
Time frame: 3 weeks after treatment
Clinical outcome: range of motion
Time frame: 6 weeks after treatment
Patient reported outcome measures: knee society score
Time frame: Preoperatively
Patient reported outcome measures: knee society score
Time frame: 3 weeks after treatment
Patient reported outcome measures: knee society score
Time frame: 6 weeks after treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Craig Della Valle, MD principal investigator
Rush University Medical Center
1 site in 1 country: see every site and its status.
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.