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

Phase 4

Completed

Conditions: Total Knee Arthroplasty

Interventions: Drug: Placebo
Drug: Hydrocortisone

Registration Number: NCT01815918

Lead Sponsor: Hospital for Special Surgery, New York

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patients receive a saline placebo before surgery, 8 hours after the first dose and 16 hours after the first dose.
Treatment	Hydrocortisone	Patients receive 3 100 mg of hydrocortisone: prior to surgery, 8 hours after the first dose and 16 hours after the first dose.

Primary Outcome Measures

Name	Time	Method
Prothrombin Fragment (PF1.2), a Marker of Thrombin Generation	Baseline and up to 4 hours following surgery	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
Plasmin-alpha-2-antiplasmin Complex (PAP), a Marker of Fibrinolysis	Baseline and up to 4 hours following surgery	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

Secondary Outcome Measures

Name	Time	Method
Hydrocortisone's Effect on Depression	one month and up to 3 months following surgery	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.
Pain Scores and Opioid Consumption	one month and up to 3 months following surgery	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.
Blinding Assessment	one month and up to 3 months following surgery	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.