Effect of Methylprednisolone on Complement Activation 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 of methylprednisolone administered prior to total knee-arthroplasty surgery. The investigators examine the effect on complement activation. 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 beneficial inhibition of the undesirable parts of the complement activation.

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. Anaesthesia and surgery are associated with a dramatic increase in the inflammatory response. The complement system participates in the disposal of products due to inflammatory damage. The complement activation generates proinflammatory mediators which amplifies the tissue damage and the inflammation. Glucocorticoid administration prior to surgery is thought to effectively reduce the inflammatory response and the activation of the complement system. The effect of glucocorticoids on specific complement markers 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 Complement Activation 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<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 and serum Pentraxin-3 concentrations from baseline (before surgery) to 48 hours after surgery |  | baseline to 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma and serum Complement Component 3 concentrations from baseline (before surgery) to 48 hours after surgery |  | baseline to 48 hours | 
| Change in plasma and serum Complement Component 4 concentrations from baseline (before surgery) to 48 hours after surgery |  | baseline to 48 hours | 
| Change in plasma and serum Mannose-binding lectin concentrations from baseline (before surgery) to 48 hours after surgery |  | baseline to 48 hours | 
| Change in plasma and serum Ficolin-1, -2 and -3 concentrations from baseline (before surgery) to 48 hours after surgery |  | baseline to 48 hours | 
| Change in plasma and serum Terminal Complement Complex concentrations from baseline (before surgery) to 48 hours after surgery |  | baseline to 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucocorticoid, Complement activation, Knee arthroplasty, total