NCT02332629

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
70

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Jan 2015

Shorter than P25 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2015

Completed
4 days until next milestone

First Submitted

Initial submission to the registry

January 5, 2015

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 7, 2015

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2016

Completed
Last Updated

April 8, 2016

Status Verified

April 1, 2016

Enrollment Period

1.2 years

First QC Date

January 5, 2015

Last Update Submit

April 7, 2016

Conditions

Osteoarthrosis

Keywords

GlucocorticoidEndothelial barrierGlycocalyxKnee arthroplasty, total

Outcome Measures

Primary Outcomes (1)

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

    baseline to 24 hours

Secondary Outcomes (3)

  • Change in plasma soluble Thrombomodulin from baseline (before surgery) to 24 hours after surgery

    baseline to 24 hours

  • Change in plasma SE-Selectin from baseline (before surgery) to 24 hours after surgery

    One day after surgery

  • Change in plasma VE-Cadherin from baseline (before surgery) to 24 hours after surgery

    baseline to 24 hours

Study Arms (2)

Methylprednisolone

ACTIVE COMPARATOR

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

Drug: Methylprednisolone

Isotonic Sodium Chloride

PLACEBO COMPARATOR

Preoperative single dose of isotonic Sodium Chloride

Drug: Isotonic Sodium Chloride

Interventions

MethylprednisoloneDRUG

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

Also known as: Solu-Medrol
Methylprednisolone
Isotonic Sodium ChlorideDRUG

Placebo

Isotonic Sodium Chloride

Eligibility Criteria

Age55 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Osteoarthrosis
  • Undergoing total unilateral knee-arthroplasty surgery
  • Speak and understand Danish
  • Have given informed consent

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Bispebjerg Hospital

Copenhagen NV, 2400, Denmark

Location

Related Publications (10)

  • 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.

    PMID: 23205862BACKGROUND

  • 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.

    PMID: 23663938BACKGROUND

  • 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.

    PMID: 24359028BACKGROUND

  • 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.

    PMID: 21895500BACKGROUND

  • 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.

    PMID: 22743373BACKGROUND

  • 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.

    PMID: 21772125BACKGROUND

  • 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.

    PMID: 17923576BACKGROUND

  • 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.

    PMID: 22290457BACKGROUND

  • 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.

    PMID: 18073553BACKGROUND

  • 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.

    PMID: 18836678BACKGROUND

MeSH Terms

Conditions

Osteoarthritis

Interventions

MethylprednisoloneMethylprednisolone HemisuccinateSodium Chloride

Condition Hierarchy (Ancestors)

ArthritisJoint DiseasesMusculoskeletal DiseasesRheumatic Diseases

Intervention Hierarchy (Ancestors)

PrednisolonePregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Study Officials

  • Viktoria Lindberg-Larsen, MD

    Section for Surgical Pathophysiology, Rigshospitalet

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, research assistant

Study Record Dates

First Submitted

January 5, 2015

First Posted

January 7, 2015

Study Start

January 1, 2015

Primary Completion

April 1, 2016

Study Completion

April 1, 2016

Last Updated

April 8, 2016

Record last verified: 2016-04

Locations

DK(1)