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

NCT ID: NCT02332629

Last Updated: 2016-04-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-31

Study Completion Date

2016-04-30

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

Conditions

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Osteoarthrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Methylprednisolone

Preoperative single high dose of Solu-Medrol 125 mg iv.

Group Type ACTIVE_COMPARATOR

Methylprednisolone

Intervention Type DRUG

Comparison of preoperative single high dose of Methylprednisolone 125 mg iv. and isotonic Sodium Chloride

Isotonic Sodium Chloride

Preoperative single dose of isotonic Sodium Chloride

Group Type PLACEBO_COMPARATOR

Isotonic Sodium Chloride

Intervention Type DRUG

Placebo

Interventions

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Methylprednisolone

Comparison of preoperative single high dose of Methylprednisolone 125 mg iv. and isotonic Sodium Chloride

Intervention Type DRUG

Isotonic Sodium Chloride

Placebo

Intervention Type DRUG

Other Intervention Names

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Solu-Medrol

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
Minimum Eligible Age

55 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bispebjerg Hospital

OTHER

Sponsor Role collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role lead

Responsible Party

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Viktoria Oline Lindberg-Larsen

MD, research assistant

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Viktoria Lindberg-Larsen, MD

Role: PRINCIPAL_INVESTIGATOR

Section for Surgical Pathophysiology, Rigshospitalet

Locations

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Bispebjerg Hospital

Copenhagen NV, , Denmark

Site Status

Countries

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Denmark

References

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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.

Reference Type BACKGROUND
PMID: 23205862 (View on PubMed)

Kehlet H. Fast-track hip and knee arthroplasty. Lancet. 2013 May 11;381(9878):1600-2. doi: 10.1016/S0140-6736(13)61003-X. No abstract available.

Reference Type BACKGROUND
PMID: 23663938 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24359028 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21895500 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22743373 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21772125 (View on PubMed)

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. doi: 10.1161/CIRCULATIONAHA.106.684852. Epub 2007 Oct 8.

Reference Type BACKGROUND
PMID: 17923576 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22290457 (View on PubMed)

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. doi: 10.1097/01.anes.0000286984.39328.96.

Reference Type BACKGROUND
PMID: 18073553 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18836678 (View on PubMed)

Other Identifiers

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HK_VL_08_2014a

Identifier Type: -

Identifier Source: org_study_id

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