Effect of Methylprednisolone on Endothelial 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 surgery (TKA). The investigators examine the effect on the endothelial glycocalyx shedding due to surgical trauma. 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 reduction in glycocalyx degradation 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 on postoperative pain, postoperative nausea and vomiting are well-documented. Postoperatively, activation and / or dysregulation of the inflammatory system influence on the endothelial glycocalyx. Damage of the vascular endothelia increases the risk of cardiovascular and thromboembolic complications. In animal studies glucocorticoids have been found to preserve the endothelial glycocalyx and the vascular barrier. The effect of glucocorticoids on human endothelial glycocalyx after surgery is unknown and calls for further investigation. This study is embedded in a primary study registrated as: NCT02319343 For further details please view the EudraCT registration: EudraCT nr.: 2014-003395-23

Official Title
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Effect of Preoperative Intravenous High Dose Methylprednisolone on Endothelial 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 og 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<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 plasma Syndecan-1 from baseline (before surgery) to 24 hours after surgery |  | baseline to 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma soluble Thrombomodulin from baseline (before surgery) to 24 hours after surgery |  | baseline to 24 hours | 
| Change in plasma SE-Selectin from baseline (before surgery) to 24 hours after surgery |  | One day after surgery | 
| Change in plasma VE-Cadherin from baseline (before surgery) to 24 hours after surgery |  | baseline to 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucocorticoid, Endothelial barrier, Glycocalyx, Knee arthroplasty, total