Medrol Dosepak for Outpatient Total Knee Arthroplasty

Total Knee Arthroplasty Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05097976
• Other study ID #: 21090203
• Status: Recruiting
• Phase: Phase 4
• Start date: March 1, 2022
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: Rush University Medical Center
• Contact: Anne DeBenedetti
• Phone: 3124322468
• Email: anne.debenedetti[@]rushortho.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 420
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Any patient undergoing primary TKA with a diagnosis of osteoarthritis

•= 18 years old

• Willingness to undergo randomization

Exclusion Criteria:

• 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

• 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

Related Conditions & MeSH terms

• Total Knee Arthroplasty

Intervention

Drug:
• Methylprednisolone
21 x 4mg tablets beginning on POD 1
• Placebo
21 sugar tablets beginning on POD 1 with standard management

Locations

Country	Name	City	State
United States	Rush Oak Brook Outpatient Center	Oak Brook	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Rush University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Opioid consumption at one-week postoperative	Relative difference in cumulative opioid consumption at Post-op day 7, measured in morphine equivalents.	one week
Secondary	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	Week 1
Secondary	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	3 weeks
Secondary	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	6 weeks
Secondary	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	Postoperative days 1 through 7 (week one)
Secondary	Patient reported outcome measures: vomiting episodes	Number of vomiting episodes, patient reported	Postoperative days 1 through 7 (week 1)
Secondary	Patient reported outcome measures: hours of sleep	Number of hours slept- patient reported	Postoperative days 1 through 7 (week one)
Secondary	Clinical outcome: range of motion	range of motion of knee	Preoperatively
Secondary	Clinical outcome: range of motion	range of motion of knee	3 weeks after treatment
Secondary	Clinical outcome: range of motion	range of motion of knee	6 weeks after treatment
Secondary	Patient reported outcome measures: knee society score	Knee society score (KSS) survey	Preoperatively
Secondary	Patient reported outcome measures: knee society score	Knee society score (KSS) survey	3 weeks after treatment
Secondary	Patient reported outcome measures: knee society score	Knee society score (KSS) survey	6 weeks after treatment