Medrol Dosepak for Outpatient Total Knee Arthroplasty

Sponsor

Rush University Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05097976

Collaborator

(none)

420

Enrollment

Location

Arms

32.1

Anticipated Duration (Months)

13.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Total Knee Arthroplasty	Drug: Methylprednisolone Drug: Placebo	Phase 4

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

Study Type:

Interventional

Anticipated Enrollment :

420 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

Investigator (surgeon) and participant (patient) will be blinded to whether they are discharged with a placebo or treatment (oral corticosteroid).

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Mar 1, 2022

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Methylprednisolone taper Methylprednisolone taper - 21 x 4mg tablets beginning on POD 1	Drug: Methylprednisolone 21 x 4mg tablets beginning on POD 1 Other Names: medrol dosepak
Placebo Comparator: Placebo taper 2.Placebo taper - 21 sugar tablets beginning on POD 1 with standard management	Drug: Placebo 21 sugar tablets beginning on POD 1 with standard management

Arm

Intervention/Treatment

Experimental: Methylprednisolone taper

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

Drug: Methylprednisolone

21 x 4mg tablets beginning on POD 1

Other Names:

medrol dosepak

Placebo Comparator: Placebo taper

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

Drug: Placebo

21 sugar tablets beginning on POD 1 with standard management

Outcome Measures

Primary Outcome Measures

Opioid consumption at one-week postoperative [one week]
Relative difference in cumulative opioid consumption at Post-op day 7, measured in morphine equivalents.

Secondary Outcome Measures

Patient reported outcome measures: Daily Visual Analogue Scale for Pain [Week 1]
Using Daily Visual Analogue Scale (VAS) pain score, scale of 1 to 10, 10 being the worst
Patient reported outcome measures : Daily Visual Analogue Scale for Pain [3 weeks]
Using Daily Visual Analogue Scale (VAS) pain score, scale of 1 to 10, 10 being the worst
Patient reported outcome measures: Daily Visual Analogue Scale for Pain [6 weeks]
Using Daily Visual Analogue Scale (VAS) pain score, scale of 1 to 10, 10 being the worst
Patient reported outcome measures: Daily Visual Analogue Scale of nausea [Postoperative days 1 through 7 (week one)]
Daily visual analogue scale- nausea score, scale of 1 to 10, 10 being the worst
Patient reported outcome measures: vomiting episodes [Postoperative days 1 through 7 (week 1)]
Number of vomiting episodes, patient reported
Patient reported outcome measures: hours of sleep [Postoperative days 1 through 7 (week one)]
Number of hours slept- patient reported
Clinical outcome: range of motion [Preoperatively]
range of motion of knee
Clinical outcome: range of motion [3 weeks after treatment]
range of motion of knee
Clinical outcome: range of motion [6 weeks after treatment]
range of motion of knee
Patient reported outcome measures: knee society score [Preoperatively]
Knee society score (KSS) survey
Patient reported outcome measures: knee society score [3 weeks after treatment]
Knee society score (KSS) survey
Patient reported outcome measures: knee society score [6 weeks after treatment]
Knee society score (KSS) survey

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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