Clinical trial NCT02332616: Effect of Methylprednisolone on Complement Activation in Patients Undergoing Total Knee-arthroplasty
Official title: Effect of Preoperative Intravenous High Dose Methylprednisolone on Complement Activation in Patients Scheduled for Total Knee-arthroplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoarthrosis
Keywords: Glucocorticoid
Complement activation
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 of methylprednisolone administered prior to total knee-arthroplasty surgery. The investigators examine the effect on complement activation.

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 beneficial inhibition of the undesirable parts of the complement activation.

Detailed description: The anti-inflammatory effects of glucocorticoids are well known. The beneficial effects on postoperative pain, postoperative nausea and vomiting are well-documented.

Anaesthesia and surgery are associated with a dramatic increase in the inflammatory response. The complement system participates in the disposal of products due to inflammatory damage. The complement activation generates proinflammatory mediators which amplifies the tissue damage and the inflammation.

Glucocorticoid administration prior to surgery is thought to effectively reduce the inflammatory response and the activation of the complement system. The effect of glucocorticoids on specific complement markers 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 or 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 and serum Pentraxin-3 concentrations from baseline (before surgery) to 48 hours after surgery
timeFrame: baseline to 48 hours
Secondary outcomes:
measure: Change in plasma and serum Complement Component 3 concentrations from baseline (before surgery) to 48 hours after surgery
timeFrame: baseline to 48 hours
measure: Change in plasma and serum Complement Component 4 concentrations from baseline (before surgery) to 48 hours after surgery
timeFrame: baseline to 48 hours
measure: Change in plasma and serum Mannose-binding lectin concentrations from baseline (before surgery) to 48 hours after surgery
timeFrame: baseline to 48 hours
measure: Change in plasma and serum Ficolin-1, -2 and -3 concentrations from baseline (before surgery) to 48 hours after surgery
timeFrame: baseline to 48 hours
measure: Change in plasma and serum Terminal Complement Complex concentrations from baseline (before surgery) to 48 hours after surgery
timeFrame: baseline to 48 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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citation: de la Motte L, Kehlet H, Vogt K, Nielsen CH, Groenvall JB, Nielsen HB, Andersen A, Schroeder TV, Lonn L. Preoperative methylprednisolone enhances recovery after endovascular aortic repair: a randomized, double-blind, placebo-controlled clinical trial. Ann Surg. 2014 Sep;260(3):540-8; discussion 548-9. doi: 10.1097/SLA.0000000000000895.
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