Clinical trial NCT05097976: Medrol Dosepak for Outpatient Total Knee Arthroplasty
Official title: An Oral Methylprednisolone Taper Within a Multimodal Analgesic Regimen After Total Knee Arthroplasty: a Double-Blind Randomized Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Total Knee Arthroplasty
Keywords: Methylprednisolone
acute postoperative pain
acute function
opioid consumption
complications following total knee arthroplasty
Lead sponsor: Rush University Medical Center
Sponsor class: OTHER
First posted: 2021-10-28
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Opioid consumption at one-week postoperative
timeFrame: one week
Secondary outcomes:
measure: Patient reported outcome measures: Daily Visual Analogue Scale for Pain
timeFrame: Week 1
measure: Patient reported outcome measures : Daily Visual Analogue Scale for Pain
timeFrame: 3 weeks
measure: Patient reported outcome measures: Daily Visual Analogue Scale for Pain
timeFrame: 6 weeks
measure: Patient reported outcome measures: Daily Visual Analogue Scale of nausea
timeFrame: Postoperative days 1 through 7 (week one)
measure: Patient reported outcome measures: vomiting episodes
timeFrame: Postoperative days 1 through 7 (week 1)
measure: Patient reported outcome measures: hours of sleep
timeFrame: Postoperative days 1 through 7 (week one)
measure: Clinical outcome: range of motion
timeFrame: Preoperatively
measure: Clinical outcome: range of motion
timeFrame: 3 weeks after treatment
measure: Clinical outcome: range of motion
timeFrame: 6 weeks after treatment
measure: Patient reported outcome measures: knee society score
timeFrame: Preoperatively
measure: Patient reported outcome measures: knee society score
timeFrame: 3 weeks after treatment
measure: Patient reported outcome measures: knee society score
timeFrame: 6 weeks after treatment
Other outcomes:
Locations:
city: Oak Brook
country: United States
facility: Rush Oak Brook Outpatient Center
state: Illinois
Study officials:
affiliation: Rush University Medical Center
name: Craig Della Valle, MD
role: PRINCIPAL_INVESTIGATOR
References: