Medrol Dosepak Taper for Delayed Post-op Recovery After TKA

Study Overview
=================
Brief Summary
-----------------
To evaluate the efficacy of a methylprednisolone taper on patients with decreased range of motion (ROM) or delayed recovery in the acute postoperative period following total knee arthroplasty (TKA). Patients with decreased ROM or delayed recovery six weeks to three months post-TKA will improve ROM and patient-reported outcomes at two weeks post-treatment initiation of methylprednisolone taper, as compared to similar patients who receive a placebo taper.

Detailed Description
-----------------
Total knee arthroplasty (TKA) is one of the most performed and efficacious orthopaedic procedures, with an estimated 7 million people living with a total knee prosthesis in 2010.1 The number of annual TKAs is predicted to increase by 85% by 2030 and 143% by 2050, equating to 1.26 million2 and 1.5 million3 procedures per year, respectively. In recent studies, knee prostheses have demonstrated their efficacy in 10-, 20-, and 25-year survival rates of 96.1%, 89.7%4, and 82.3%5, respectively. Similarly, comparing functional and patient-reported outcomes before and after surgery have confirmed the high success rate achieved with this procedure.6-10 However, recovery following total knee arthroplasty (TKA) in the acute postoperative period is variable. Most clinical improvements are achieved within the first three months postoperatively but can continue up to one year.11 There is currently a paucity of data evaluating the efficacy of oral corticosteroids in the six-week to three-month postoperative period in slowly recovering patients. Few treatments have been studied for patients who fail to achieve early range of motion or pain reduction milestones in the perioperative period. Periarticular and systemic corticosteroids improve pain and function in the immediate postoperative period, without an increase in adverse events.12-16 Additional doses of corticosteroids administered at 24 and 48 hours postoperatively have demonstrated greater improvements in pain and ROM compared to perioperative administration, with no difference in complication rates.17-20 However, few studies have evaluated the use of oral corticosteroids within a multimodal pain management regimen. Gardiner et al. evaluated low-dose steroids 10 days immediately following lumbar laminectomy and/or discectomy, in addition to a standard opioid regimen, and reported decreased subjective pain scores.21 Gottshalk et al. reported decreased patient reported pain from postoperative days 4-7 in early published results of a randomized controlled trial investigating administration of a methylprednisolone taper immediately following distal radius repair.22 Importantly, the current literature demonstrates low- and short-dose corticosteroids are safe.23 Intraoperative corticosteroids have been shown to improve pain and function in the acute postoperative period, and additional doses in the immediate postoperative period can potentiate and prolong this beneficiary effect, without increasing adverse events. Therefore, a methylprednisolone taper six weeks post-TKA may benefit patients experiencing decreased ROM or delayed recovery, including residual pain. Following TKA, care is taken to control pain, swelling, and stiffness, all of which may contribute to delayed recovery. For instance, more than 20% of TKA patients develop postoperative stiffness,24 known as arthrofibrosis, accounting for an estimated 28% of 90-day hospital readmissions.25 In treating patients with delayed recovery, corticosteroids are of particular interest because of its potent anti-inflammatory effect, evidenced by its ability to decrease postoperative levels of IL-6 and CRP.15 Corticosteroids block prostaglandin synthesis, which is responsible for sensitizing nociceptive pain receptors, and reduce vascular permeability, which causes edema following surgery.26, 27 Therefore, by reducing pain and edema, corticosteroids may allow for more effective physical therapy sessions and more rapid improvement in ROM and recovery following TKA. To the best of our knowledge, this is the first study to investigate the utility of a methylprednisolone taper six weeks to three months postoperatively following TKA. The authors present a double-blinded, randomized-controlled trial evaluating the role of a methylprednisolone taper on patients with decreased ROM or delayed recovery in the acute postoperative period.

Official Title
-----------------
Methylprednisolone Taper to Treat Delayed Post-Operative Recovery After Total Knee Arthroplasty: a Double-Blind Randomized Controlled Trial

Conditions
-----------------
Total Knee Arthroplasty

Intervention / Treatment
-----------------
* Drug: Methylprednisolone
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Any patient undergoing primary TKA with a diagnosis of osteoarthritis ≥ 18 years old ROM <90° by 3 weeks postoperatively without improvement to >90° by 6 weeks Requiring a 30-pill oxycodone refill NSAID allergy Thigh circumference discrepancy >2cm between legs from 3 to 6 weeks Defense and Veterans Pain Rating Scale (DVPRS) > 5 between 3 and 6 weeks 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 or renal disease Uncontrolled diabetes Immunosuppression ≤ 18 years old Inability to take oral medications Unable to provide consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Methylprednisolone taper<br>21 x 4mg tablets at 6 weeks, qualifying for MUA if ROM <90° at 8 weeks | Drug: Methylprednisolone<br>* 21 x 4mg tablets at 6 weeks, qualifying for MUA if ROM <90° at 8 weeks<br>|
| Placebo Comparator: Placebo taper<br>21 sugar tablets at 6 weeks with standard management, qualifying for MUA if ROM <90° at 8 weeks | Drug: Placebo<br>* 21 sugar tablets at 6 weeks with standard management, qualifying for MUA if ROM <90° at 8 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Range of Motion in Degrees at Pre and Post Treatment | Range of motion (ROM) from pre-treatment to six weeks following treatment. Patients started treatment after total knee replacement surgery and presented to clinic with at least one inclusion criteria to be enrolled. Range of motion in degrees is taken at each visit by a clinician (standard of care), starting at zero degrees (straight leg) to about 135 degrees. The ROM was documented as part of consenting and enrollment into study. Subjects returned to the office at 6 weeks post treatment where ROM was performed in a clinic setting once again and documented. ROM is done using a goniometer by a clinician in each clinic. This study was terminated early, therefore of the 4 enrolled, zero were randomized to the placebo group. Only 1 of the four subjects completed the 6 weeks, however, ROM was captured on all as standard of care. | Baseline, Week 6 Following Treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Reported Outcome Measures: Post Treatment Pain Scores (6 Weeks) | Using daily defense and veterans pain rating scale (DVPRS) on a scale of 1 to 10, 10 being the worst. Please note, only one patient made it to the 6 week post treatment mark of the 4 enrolled. The study was terminated and none of the patients were randomized to the placebo group. All other patients followed up but were not interested in continuing. No range could be provided given only one subject answered and completed this visit | 6 weeks post treatment | 
| Patient Reported Outcome Measures: Pre Treatment Pain Scores Using Knee Society Scores | Knee society score (KSS); done standard of care on a scale of 0-100, where 100 means a more functional knee **Please note, the study was terminated early, only 4 subjects were enrolled and none were randomized to the placebo group. | pre treatment | 
| Patient Reported Outcome Measures: Post Treatment Pain Scores | Knee society score (KSS); done standard of care on a scale of 0-100, where 100 means a more functional knee. **Please note, the study was terminated early, only 4 subjects were enrolled and none were randomized to the placebo group. At 3 weeks post treatment, only 3 of the 4 subjects enrolled were still part of the study. | 3 weeks post treatment | 
| Patient Reported Outcome Measures: Post Treatment Pain Scores | Knee society score (KSS); done standard of care on a scale of 0-100, where 100 means a more functional knee. **Please note, the study was terminated early, only 4 subjects were enrolled and none were randomized to the placebo group. This is a standard of care survey available on all subjects. | 6 weeks post treatment | 
| Patient Reported Outcome Measures:(Immediate) Post Treatment Pain Scores | Using Daily Visual Analogue Scale (VAS) pain score, which measures intensity of pain on a scale of 0 (no pain) to 10 (worst pain possible). **Please note, this study was terminated early, only enrolling 4 patients, none were randomized to the placebo group. | Days 1 through 6 following treatment | 
| Patient Reported Outcome Measures: Overall Assessment of Knee After Surgery and Treatment | Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR), a survey given to patients standard of care containing 7 questions. The score ranges from 0 to 100 where zero represents total disability and 100 represents a perfect knee health. | pre treatment | 
| Patient Reported Outcome Measures: Overall Assessment of Knee After Surgery and Treatment | Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR), a survey given to patients standard of care containing 7 questions. The score ranges from 0 to 100 where zero represents total disability and 100 represents a perfect knee health. | 6 weeks after treatment | 
| Patient Reported Outcome Measures: Overall Assessment of Knee Before Treatment | Veterans Rand 12-Item Health Survey (VR-12), a survey of 12 questions to measure health relating to patient's quality of life. Scored as summary of mental and physical, measure in standard deviations. The scale range is 0 to 100, where a score of 100 represents the best physical and mental health and zero is the worst outcome. | pre treatment | 
| Patient Reported Outcome Measures: Overall Assessment of Knee 6 Weeks After Treatment | VR-12: Assesses physical functioning, physical/ mental limitations. Scored as summary of mental and physical, measure in standard deviations. The scale range is 0 to 100, where a score of 100 represents the best physical and mental health and zero is the worst outcome. | 6 weeks after treatment | 
| Patient Reported Outcome Measures: Overall Assessment of Knee Before Treatment | Single Assessment Numeric Evaluation (SANE), a single-question patient rating of 0-100, scoring their function to the area being treated. Zero represents a poor functional knee and 100 is the best functioning. | pre treatment | 
| Patient Reported Outcome Measures: Overall Assessment of Knee 6 Weeks After Treatment | Single Assessment Numeric Evaluation (SANE), a single-question patient rating of 0-100, scoring their function to the area being treated. Zero represents a poor functional knee and 100 is the best functioning. | 6 weeks after treatment | 
| Patient Reported Outcome Measures: Overall Assessment of Knee Prior to Treatment | Forgotten Joint Score (FJS) is a survey scored ranging from 0 to 100, where a high score indicates a high degree of a forgetting they have an artificial joint, which is an ideal outcome. | pre treatment | 
| Patient Reported Outcome Measures: Overall Assessment of Knee 6 Wks After Treatment | Forgotten Joint Score (FJS) is a survey scored ranging from 0 to 100, where a high score indicates a high degree of a forgetting they have an artificial joint, which is an ideal outcome. | 6 weeks after treatment | 
| Patient Reported Outcome Measures: Overall Assessment of Knee Prior to Treatment | UCLA activity score, on a scale of 1 to 10 where 10 is the most active patient with examples of activities | pre treatment | 
| Patient Reported Outcome Measures: Overall Assessment of Knee 6 Weeks After Treatment | UCLA activity score, on a scale of 1 to 10 where 10 is the most active patient with examples of activities | 6 weeks after treatment | 
| Number of Participants With Complications Following Treatment | Manipulations under anesthesia (MUAs) following total knee arthroplasty surgery and treatment | within 90 days after initial total knee arthroplasty | 
| Adverse Events or Outcomes Outside of Manipulations Under Anesthesia | Adverse outcomes including infection, avascular necrosis, and 90-day readmission rates | within 90 days after initial total knee arthroplasty | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Methylprednisolone, Delayed recover, range of motion