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

Phase 3

Completed

• Conditions: Osteoarthrosis
• Interventions: Drug: Isotonic Sodium Chloride; Drug: Methylprednisolone

• Registration Number: NCT02332629
• Lead Sponsor: Rigshospitalet, Denmark

Brief Summary

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

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

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2015-01-05
• Study First Submitted QC: 2015-01-06
• Study First Posted: 2015-01-07
• Status Verified: 2016-04
• Primary Completion: 2016-04
• Study Completion: 2016-04
• Last Update Submitted: 2016-04-07
• Last Update Posted: 2016-04-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Isotonic Sodium Chloride	Isotonic Sodium Chloride	Preoperative single dose of isotonic Sodium Chloride
Methylprednisolone	Methylprednisolone	Preoperative single high dose of Solu-Medrol 125 mg iv.

Primary Outcome Measures

Name	Time	Method
Change in plasma Syndecan-1 from baseline (before surgery) to 24 hours after surgery	baseline to 24 hours

Secondary Outcome Measures

Name	Time	Method
Change in plasma SE-Selectin from baseline (before surgery) to 24 hours after surgery	One day after surgery
Change in plasma soluble Thrombomodulin from baseline (before surgery) to 24 hours after surgery	baseline to 24 hours
Change in plasma VE-Cadherin from baseline (before surgery) to 24 hours after surgery	baseline to 24 hours

Trial Locations

Locations (1)

Bispebjerg Hospital; 🇩🇰 Copenhagen NV, Denmark