Clinical trial NCT01815918: Effect of Low Dose Corticosteroids on Perioperative Markers of Thrombosis and Fibrinolysis in Total Knee Arthroplasty
Official title: The Effect of Low Dose Corticosteroids on Perioperative Markers of Thrombosis and Fibrinolysis in Total Knee Arthroplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Total Knee Arthroplasty
Keywords: Orthopedic Procedures
Prostheses and Implants
Joint Prosthesis
Knee Prosthesis
Arthroplasty, Knee
Thromboembolism
Inflammation
B-Cell Differentiation Factor-2
Differentiation Factor-2, B-Cell
B-Cell Stimulatory Factor-2
BSF-2
IFN-beta 2
MGI-2
Interleukin-6 (IL-6)
Steroids
Pregnenediones
Hydrocortisone
Physiological Effects of Drugs
Therapeutic Uses
Lead sponsor: Hospital for Special Surgery, New York
Sponsor class: OTHER
First posted: 2013-03-21
Enrollment: 60
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Prothrombin Fragment (PF1.2), a Marker of Thrombin Generation
timeFrame: Baseline and up to 4 hours following surgery
measure: Plasmin-alpha-2-antiplasmin Complex (PAP), a Marker of Fibrinolysis
timeFrame: Baseline and up to 4 hours following surgery
Secondary outcomes:
measure: Hydrocortisone's Effect on Depression
timeFrame: one month and up to 3 months following surgery
measure: Pain Scores and Opioid Consumption
timeFrame: one month and up to 3 months following surgery
measure: Blinding Assessment
timeFrame: one month and up to 3 months following surgery
Other outcomes:
Locations:
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
Study officials:
affiliation: Hospital for Special Surgery, New York
name: Kethy Jules-Elysée, M.D.
role: PRINCIPAL_INVESTIGATOR
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