Effect of Low Dose Corticosteroids on Perioperative Markers of Thrombosis and Fibrinolysis in Total Knee Arthroplasty

Total Knee Arthroplasty Clinical Trial

Official title:

The Effect of Low Dose Corticosteroids on Perioperative Markers of Thrombosis and Fibrinolysis in Total Knee Arthroplasty

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01815918
• Other study ID #: 2012-054
• Status: Completed
• Phase: Phase 4
• Start date: February 2011
• Est. completion date: April 2012

Study information

• Verified date: April 2022
• Source: Hospital for Special Surgery, New York
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

One postoperative complication following unilateral or bilateral total knee arthroplasty is thrombosis (blood clot formation). In this prospective, double-blinded randomized controlled clinical trial, researchers are investigating the effect of steroids on biochemical markers of thrombosis. Furthermore, elevated cellular markers of thrombosis (specifically IL-6) have been linked to postoperative depression following total knee arthroplasty surgery. Hence the investigators are also checking if use of hydrocortisone, a steroid, may help reduce the incidence of postoperative depression. Other studies have shown that surgery causes some reaction in the body that is consistent with inflammation. When the inflammation is extensive, it may affect different parts of the body. It may also lead to clotting disorders and result in blood clots. In a previous study by this principal investigator (see reference 22, "Use of low-dose steroids in decreasing cytokine release during bilateral total knee arthroplasty"), hydrocortisone was administered over 24 hours following surgery to patients who underwent bilateral total knee arthroplasty. The investigator found lower levels of cellular markers consistent with inflammation (specifically the protein, IL-6). Steroid use also showed additional benefits, such as decreased pain and better range of motion at the knee. In this study, investigators recruit patients undergoing total knee arthroplasty surgery. Patients are randomized to receive three 100 mg doses of hydrocortisone or three doses of a saline placebo. In addition to analyzing patients' blood samples for hydrocortisone's effect on clotting factors (i.e. IL-6), investigators record patients' pain scores and patients' oral analgesic use. To assess patients' well-being, patients are contacted one month and 3 months following their surgeries and administered the Patient Health Questionnaire (see reference 23, "The PHQ-9: validity of a brief depression severity measure.") arthroplasty.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 90 Years

Eligibility

Inclusion Criteria:

• All patients undergoing unilateral or bilateral total knee replacement
• Age 50-90

Exclusion Criteria:

• All patients on steroid therapy regardless of dose or duration of treatment or those requiring stress-dose steroids preoperatively
• Patients who are smokers
• Patients under 50 years of age
• Patients over 90 years of age
• Patients with diabetes
• Patients with a prior history of corticosteroid intolerance
• Patients with previous complications of steroid use

Related Conditions & MeSH terms

• Thrombosis
• Total Knee Arthroplasty

Intervention

Drug:
• Hydrocortisone
Patients randomized to treatment arm will three doses of 100 mg of hydrocortisone at the following times: prior to surgery, 8 hours after the first dose and 16 hours after the first dose.
• Placebo
Patients receive placebo prior to surgery, 8 hours after the first dose and 16 hours after the first dose.

Locations

Country	Name	City	State
United States	Hospital for Special Surgery	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hospital for Special Surgery, New York

Country where clinical trial is conducted

United States, 

References & Publications (23)

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Collen D, Hoylaerts MF. Relationship between inflammation and venous thromboembolism as studied by microparticle assessment in plasma. J Am Coll Cardiol. 2005 May 3;45(9):1472-3. — View Citation

Cremeans-Smith JK, Soehlen S, Greene K, Alexander T, Delahanty DL. In-hospital levels of C-reactive protein and IL-6 predict post-operative depressive symptoms among patients undergoing total knee replacement surgery. Brain Behav Immun. 2009 Nov;23(8):1096-103. doi: 10.1016/j.bbi.2009.06.148. Epub 2009 Jun 24. — View Citation

Fox EA, Kahn SR. The relationship between inflammation and venous thrombosis. A systematic review of clinical studies. Thromb Haemost. 2005 Aug;94(2):362-5. Review. — View Citation

Høgevold HE, Høiseth A, Reikerås O. Effect of high-dose corticosteroids on the incidence of deep vein thrombosis after total hip replacement. Arch Orthop Trauma Surg. 1991;111(1):29-31. — View Citation

Jansen NJ, van Oeveren W, van den Broek L, Oudemans-van Straaten HM, Stoutenbeek CP, Joen MC, Roozendaal KJ, Eysman L, Wildevuur CR. Inhibition by dexamethasone of the reperfusion phenomena in cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1991 Oct;102(4):515-25. — View Citation

Jules-Elysee KM, Lipnitsky JY, Patel N, Anastasian G, Wilfred SE, Urban MK, Sculco TP. Use of low-dose steroids in decreasing cytokine release during bilateral total knee replacement. Reg Anesth Pain Med. 2011 Jan-Feb;36(1):36-40. doi: 10.1097/AAP.0b013e31820306c5. — View Citation

Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. — View Citation

Levi M, Cromheecke ME, de Jonge E, Prins MH, de Mol BJ, Briët E, Büller HR. Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints. Lancet. 1999 Dec 4;354(9194):1940-7. — View Citation

Levi M, van der Poll T. Two-way interactions between inflammation and coagulation. Trends Cardiovasc Med. 2005 Oct;15(7):254-9. Review. — View Citation

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Medcalf RL, Van den Berg E, Schleuning WD. Glucocorticoid-modulated gene expression of tissue- and urinary-type plasminogen activator and plasminogen activator inhibitor 1 and 2. J Cell Biol. 1988 Mar;106(3):971-8. — View Citation

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Parvizi J, Mui A, Purtill JJ, Sharkey PF, Hozack WJ, Rothman RH. Total joint arthroplasty: When do fatal or near-fatal complications occur? J Bone Joint Surg Am. 2007 Jan;89(1):27-32. — View Citation

Pulido L, Ghanem E, Joshi A, Purtill JJ, Parvizi J. Periprosthetic joint infection: the incidence, timing, and predisposing factors. Clin Orthop Relat Res. 2008 Jul;466(7):1710-5. doi: 10.1007/s11999-008-0209-4. Epub 2008 Apr 18. — View Citation

Reikeras O, Clementsen T. Thrombosis markers in hip versus knee arthroplasty: a pilot study. J Orthop Surg (Hong Kong). 2009 Dec;17(3):291-5. — View Citation

Sharrock NE, Go G, Sculco TP, Salvati EA, Westrich GH, Harpel PC. Dose response of intravenous heparin on markers of thrombosis during primary total hip replacement. Anesthesiology. 1999 Apr;90(4):981-7. — View Citation

van der Poll T, Levi M, Hack CE, ten Cate H, van Deventer SJ, Eerenberg AJ, de Groot ER, Jansen J, Gallati H, Büller HR, et al. Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees. J Exp Med. 1994 Apr 1;179(4):1253-9. — View Citation

van Deventer SJ, Büller HR, ten Cate JW, Aarden LA, Hack CE, Sturk A. Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood. 1990 Dec 15;76(12):2520-6. — View Citation

van Giezen JJ, Chung-A-Hing JE, Vegter CB, Bouma BN, Jansen JW. Fibrinolytic activity in blood is distributed over a cellular and the plasma fraction which can be modulated separately. Thromb Haemost. 1994 Dec;72(6):887-92. — View Citation

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* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prothrombin Fragment (PF1.2), a Marker of Thrombin Generation	Study patients received 100 mg of intravenous hydrocortisone 2 h prior to surgery, and controls received normal saline. Blood samples, drawn pre-incision and at 4 h post tourniquet release, were assayed for PF1.2 and PAP	Baseline and up to 4 hours following surgery
Primary	Plasmin-alpha-2-antiplasmin Complex (PAP), a Marker of Fibrinolysis	Study patients received 100 mg of intravenous hydrocortisone 2 h prior to surgery, and controls received normal saline. Blood samples, drawn pre-incision and at 4 h post tourniquet release, were assayed for PF1.2 and PAP	Baseline and up to 4 hours following surgery
Secondary	Hydrocortisone's Effect on Depression	Elevated IL-6 has been linked to post-operative depression following total knee replacement surgery. Patients will be administered the patient health questionnaire (PHQ-9) one month and 3 months following surgery to assess their well-being.	one month and up to 3 months following surgery
Secondary	Pain Scores and Opioid Consumption	Pain scores (rated on a scale of 0-10) will be taken throughout study participation. We will also record analgesic use to see if patients who received hydrocortisone needed fewer pain killers to control their postoperative pain.	one month and up to 3 months following surgery
Secondary	Blinding Assessment	Throughout each patient's study participation, the patient and the data collector will be asked to guess their treatment status. This helps ascertain if there is an association between blinding status, treatment effect and the depression measure.	one month and up to 3 months following surgery

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