Effect of Methylprednisolone on Quadriceps Muscle Function in Patients Undergoing Total Knee-arthroplasty

Study Overview
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Brief Summary
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This study evaluates the pathophysiological effects of a single dose Methylprednisolone administered prior to total knee-arthroplasty (TKA). The investigators examine the effect on thigh muscle function to evaluate the efficacy of Methylprednisolone on knee-extension strength at discharge after TKA. Half of participants will receive intravenous Solu-Medrol 125 mg, while the other half will receive placebo. The investigators hypothesize that the group receiving Methylprednisolone will experience smaller loss of knee-extension strength compared to the placebo-group, early after TKA.

Detailed Description
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The anti-inflammatory effects of glucocorticoids are well known. The beneficial effects in postoperative pain, postoperative nausea and vomiting are well-documented. Knee-arthroplasty surgery and the inflammatory stress response in general affect the potential of recovery. The quadriceps muscle strength is shown to be reduced significantly (80%) early after surgery. The mechanism is thought related to inhibitory reflexes and pain caused by surgical induced inflammation around the knee joint. The effect of glucocorticoids on the quadriceps muscle function after knee-arthroplasty surgery is unknown and calls for further investigation. The study is to be considered as explorative. The primary analysis of the primary outcome measure is a comparison of the changes in knee extension strength from baseline to 48 hours postoperatively between the two groups. For calculation of sample size the average loss of strength from baseline (before surgery) to 48 hours after TKA-surgery being 0.8 Nm/kg body weight (SD=0.39, Holm et al. 2010), a risk of type I errors 5% and a risk of type II errors 20% (80% power) were used. The sample size is estimated to reveal a group difference in knee extension strength of minimum 40%. The primary analysis is carried out on all included patients (intention-to-treat) with baseline values as covariate. Secondary exploratory per-protocol analysis might be performed. Missing outcomes will be analysed using multiple imputation due to expected strong time trends. The secondary outcome measures; a group difference of 6 sec. (Timed Up & Go) and 2 cm (knee circumference) are considered clinically relevant. The statistical power is based on the calculation outlined above using the same test prerequisites. For further details please also view the European Clinical Trials Database (EudraCT) registration: EudraCT nr.: 2014-003395-23

Official Title
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Effect of Preoperative Intravenous High Dose Methylprednisolone on Quadriceps Muscle Function in Patients Scheduled for Total Knee-arthroplasty

Conditions
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Osteoarthrosis

Intervention / Treatment
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* Drug: Methylprednisolone
* Drug: Isotonic Sodium Chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Osteoarthrosis Undergoing total unilateral knee-arthroplasty surgery Speak and understand Danish Have given informed consent Exclusion Criteria: Revision, bilateral or uni chamber knee-arthroplasty surgery General anaesthesia Allergy or intolerance towards Methylprednisolone Local or systemic infection Permanent systemic treatment with steroids within 30 days preoperatively Insulin-dependent diabetes Active treatment of ulcer within 3 months preoperatively Cancer disease Autoimmune disease incl. rheumatoid arthritis Pregnant or breast feeding women Menopause <1 year

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Methylprednisolone<br>Preoperative single high dose of Solu-Medrol 125 mg iv. | Drug: Methylprednisolone<br>* Comparison of preoperative single high dose of Methylprednisolone 125 mg iv. and isotonic Sodium Chloride (placebo)<br>* Other names: Solu-Medrol;|
| Placebo Comparator: Isotonic Sodium Chloride<br>Preoperative single dose of isotonic Sodium Chloride. | Drug: Isotonic Sodium Chloride<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in isometric knee extension strength measured as Nm/kg from baseline to 48 hours after surgery |  | two days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Timed Up & Go (sec.) from baseline (before surgery) to 48 hours after surgery |  | two days after surgery | 
| Change in knee circumference (cm) from baseline (before surgery) to 48 hours after surgery |  | two days after surgery | 
| Change in pain intensity from baseline (before surgery) to 48 hours after surgery |  | two days after surgery | 
| Change in concentration of C-reactive Protein from baseline (before surgery) to 48 hours after surgery |  | two days after suregry | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucocorticoid, Quadriceps muscle function, Knee arthroplasty, total