Clinical trial NCT02332629: Effect of Methylprednisolone on Endothelial Function in Patients Undergoing Total Knee-arthroplasty
Official title: Effect of Preoperative Intravenous High Dose Methylprednisolone on Endothelial Function in Patients Scheduled for Total Knee-arthroplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoarthrosis
Keywords: Glucocorticoid
Endothelial barrier
Glycocalyx
Knee arthroplasty, total
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Bispebjerg Hospital
First posted: 2015-01-07
Enrollment: 70
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

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

Eligibility criteria: 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

Primary outcomes:
measure: Change in plasma Syndecan-1 from baseline (before surgery) to 24 hours after surgery
timeFrame: baseline to 24 hours
Secondary outcomes:
measure: Change in plasma soluble Thrombomodulin from baseline (before surgery) to 24 hours after surgery
timeFrame: baseline to 24 hours
measure: Change in plasma SE-Selectin from baseline (before surgery) to 24 hours after surgery
timeFrame: One day after surgery
measure: Change in plasma VE-Cadherin from baseline (before surgery) to 24 hours after surgery
timeFrame: baseline to 24 hours
Other outcomes:
Locations:
city: Copenhagen NV
country: Denmark
facility: Bispebjerg Hospital
Study officials:
affiliation: Section for Surgical Pathophysiology, Rigshospitalet
name: Viktoria Lindberg-Larsen, MD
role: PRINCIPAL_INVESTIGATOR
References:
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