Effect of Methylprednisolone on Complement Activation in Patients Undergoing Total Knee-arthroplasty

Condition(s) targeted: Osteoarthrosis

Intervention: Methylprednisolone (Drug); Isotonic Sodium Chloride (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Rigshospitalet, Denmark

Official(s) and/or principal investigator(s):
Viktoria Lindberg-Larsen, MD, Principal Investigator, Affiliation: Section for Surgical Pathophysiology, Rigshospitalet

Overall contact:
Henrik Kehlet, Professor, Phone: 0045 35454974, Email: Henrik.Kehlet@regionh.dk

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.

Official title: Effect of Preoperative Intravenous High Dose Methylprednisolone on Complement Activation in Patients Scheduled for Total Knee-arthroplasty

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

Primary outcome: Change in plasma and serum Pentraxin-3 concentrations from baseline (before surgery) to 48 hours after surgery

Secondary outcome:

Change in plasma and serum Complement Component 3 concentrations from baseline (before surgery) to 48 hours after surgery

Change in plasma and serum Complement Component 4 concentrations from baseline (before surgery) to 48 hours after surgery

Change in plasma and serum Mannose-binding lectin concentrations from baseline (before surgery) to 48 hours after surgery

Change in plasma and serum Ficolin-1, -2 and -3 concentrations from baseline (before surgery) to 48 hours after surgery

Change in plasma and serum Terminal Complement Complex concentrations from baseline (before surgery) to 48 hours after surgery

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

Minimum age: 55 Years. Maximum age: 80 Years. Gender(s): Both.

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

Henrik Kehlet, Professor, Phone: 0045 35454974, Email: Henrik.Kehlet@regionh.dk

Bispebjerg Hospital, Copenhagen NV 2400, Denmark; Recruiting
Jens Bagger, MD, Phone: 0045 35312192, Email: Jens.Bagger@regionh.dk

Related publications:

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.

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

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.

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.

Abdelmalak BB, Bonilla AM, Yang D, Chowdary HT, Gottlieb A, Lyden SP, Sessler DI. The hyperglycemic response to major noncardiac surgery and the added effect of steroid administration in patients with and without diabetes. Anesth Analg. 2013 May;116(5):1116-22. doi: 10.1213/ANE.0b013e318288416d. Epub 2013 Apr 4.

Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear T, Vender JS, Gray J, Landry E. The effect of single low-dose dexamethasone on blood glucose concentrations in the perioperative period: a randomized, placebo-controlled investigation in gynecologic surgical patients. Anesth Analg. 2014 Jun;118(6):1204-12. doi: 10.1213/ANE.0b013e3182a53981.

de la Motte L, Kehlet H, Vogt K, Nielsen CH, Groenvall JB, Nielsen HB, Andersen A, Schroeder TV, Lönn 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.

Dieleman JM, Nierich AP, Rosseel PM, van der Maaten JM, Hofland J, Diephuis JC, Schepp RM, Boer C, Moons KG, van Herwerden LA, Tijssen JG, Numan SC, Kalkman CJ, van Dijk D; Dexamethasone for Cardiac Surgery (DECS) Study Group. Intraoperative high-dose dexamethasone for cardiac surgery: a randomized controlled trial. JAMA. 2012 Nov 7;308(17):1761-7. doi: 10.1001/jama.2012.14144.

Starting date: January 2015
Last updated: January 29, 2015