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

Osteoarthrosis Clinical Trial

Official title:

Effect of Preoperative Intravenous High Dose Methylprednisolone on Endothelial Function in Patients Scheduled for Total Knee-arthroplasty

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02332629
• Other study ID #: HK_VL_08_2014a
• Status: Completed
• Phase: Phase 3
• First received: January 5, 2015
• Last updated: April 7, 2016
• Start date: January 2015
• Est. completion date: April 2016

Study information

• Verified date: April 2016
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Health and Medicines Authority
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 55 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Joint Diseases
• Osteoarthritis
• Osteoarthrosis

Intervention

Drug:
• Methylprednisolone
Comparison of preoperative single high dose of Methylprednisolone 125 mg iv. and isotonic Sodium Chloride
• Isotonic Sodium Chloride
Placebo

Locations

Country	Name	City	State
Denmark	Bispebjerg Hospital	Copenhagen NV

Sponsors (2)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Bispebjerg Hospital

Country where clinical trial is conducted

Denmark, 

References & Publications (10)

Chappell D, Hofmann-Kiefer K, Jacob M, Rehm M, Briegel J, Welsch U, Conzen P, Becker BF. TNF-alpha induced shedding of the endothelial glycocalyx is prevented by hydrocortisone and antithrombin. Basic Res Cardiol. 2009 Jan;104(1):78-89. doi: 10.1007/s00395-008-0749-5. Epub 2008 Oct 3. — View Citation

Chappell D, Jacob M, Hofmann-Kiefer K, Bruegger D, Rehm M, Conzen P, Welsch U, Becker BF. Hydrocortisone preserves the vascular barrier by protecting the endothelial glycocalyx. Anesthesiology. 2007 Nov;107(5):776-84. — View Citation

Husted H. Fast-track hip and knee arthroplasty: clinical and organizational aspects. Acta Orthop Suppl. 2012 Oct;83(346):1-39. doi: 10.3109/17453674.2012.700593. Review. — View Citation

Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients. Ann Surg. 2011 Aug;254(2):194-200. doi: 10.1097/SLA.0b013e318226113d. — View Citation

Kehlet H. Fast-track hip and knee arthroplasty. Lancet. 2013 May 11;381(9878):1600-2. doi: 10.1016/S0140-6736(13)61003-X. — View Citation

Khan SK, Malviya A, Muller SD, Carluke I, Partington PF, Emmerson KP, Reed MR. Reduced short-term complications and mortality following Enhanced Recovery primary hip and knee arthroplasty: results from 6,000 consecutive procedures. Acta Orthop. 2014 Feb;85(1):26-31. doi: 10.3109/17453674.2013.874925. Epub 2013 Dec 20. — View Citation

Malviya A, Martin K, Harper I, Muller SD, Emmerson KP, Partington PF, Reed MR. Enhanced recovery program for hip and knee replacement reduces death rate. Acta Orthop. 2011 Oct;82(5):577-81. doi: 10.3109/17453674.2011.618911. Epub 2011 Sep 6. — View Citation

Ostrowski SR, Johansson PI. Endothelial glycocalyx degradation induces endogenous heparinization in patients with severe injury and early traumatic coagulopathy. J Trauma Acute Care Surg. 2012 Jul;73(1):60-6. doi: 10.1097/TA.0b013e31825b5c10. — View Citation

Rehm M, Bruegger D, Christ F, Conzen P, Thiel M, Jacob M, Chappell D, Stoeckelhuber M, Welsch U, Reichart B, Peter K, Becker BF. Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia. Circulation. 2007 Oct 23;116(17):1896-906. Epub 2007 Oct 8. — View Citation

Woodcock TE, Woodcock TM. Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. Br J Anaesth. 2012 Mar;108(3):384-94. doi: 10.1093/bja/aer515. Epub 2012 Jan 29. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in plasma Syndecan-1 from baseline (before surgery) to 24 hours after surgery		baseline to 24 hours	No
Secondary	Change in plasma soluble Thrombomodulin from baseline (before surgery) to 24 hours after surgery		baseline to 24 hours	No
Secondary	Change in plasma SE-Selectin from baseline (before surgery) to 24 hours after surgery		One day after surgery	No
Secondary	Change in plasma VE-Cadherin from baseline (before surgery) to 24 hours after surgery		baseline to 24 hours	No