Total Knee Arthroplasty
Conditions
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
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.
Interventions
DRUGHydrocortisone
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.
DRUGPlacebo
Patients receive placebo prior to surgery, 8 hours after the first dose and 16 hours after the first dose.
Sponsors
Hospital for Special Surgery, New York
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients receive a saline placebo before 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. | 12 |
| Treatment Patients receive 3 100 mg of hydrocortisone: prior to surgery, 8 hours after the first dose and 16 hours after the first dose.
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. | 11 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 15 | 15 |
| Overall Study | Patient samples not analyzable | 3 | 4 |
Baseline characteristics
| Characteristic | Placebo | Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 8 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 3 Participants | 7 Participants |
| Age, Continuous | 66 years STANDARD_DEVIATION 8 | 68 years STANDARD_DEVIATION 6 | 67 years STANDARD_DEVIATION 7 |
| Region of Enrollment United States | 12 participants | 11 participants | 23 participants |
| Sex: Female, Male Female | 9 Participants | 8 Participants | 17 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 11 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 |
Outcome results
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
Time frame: Baseline and up to 4 hours following surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasmin-alpha-2-antiplasmin Complex (PAP), a Marker of Fibrinolysis | Baseline | 623.3 ug/L | Standard Deviation 324.8 |
| Placebo | Plasmin-alpha-2-antiplasmin Complex (PAP), a Marker of Fibrinolysis | 4 hs | 1086.8 ug/L | Standard Deviation 536.3 |
| Treatment | Plasmin-alpha-2-antiplasmin Complex (PAP), a Marker of Fibrinolysis | Baseline | 808.4 ug/L | Standard Deviation 372.1 |
| Treatment | Plasmin-alpha-2-antiplasmin Complex (PAP), a Marker of Fibrinolysis | 4 hs | 1638.6 ug/L | Standard Deviation 823.2 |
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
Time frame: Baseline and up to 4 hours following surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Prothrombin Fragment (PF1.2), a Marker of Thrombin Generation | Baseline | 263.6 pMol/L | Standard Deviation 158.6 |
| Placebo | Prothrombin Fragment (PF1.2), a Marker of Thrombin Generation | 4s | 935.8 pMol/L | Standard Deviation 331.9 |
| Treatment | Prothrombin Fragment (PF1.2), a Marker of Thrombin Generation | Baseline | 266.5 pMol/L | Standard Deviation 146.9 |
| Treatment | Prothrombin Fragment (PF1.2), a Marker of Thrombin Generation | 4s | 615.9 pMol/L | Standard Deviation 357.7 |
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.
Time frame: one month and up to 3 months following surgery
Population: Outcome could not be analyzed because patients could not be reached to collect data at one month and up to 3 months 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.
Time frame: one month and up to 3 months following surgery
Population: Outcome could not be analyzed because patients could not be reached to collect data at 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.
Time frame: one month and up to 3 months following surgery
Population: Outcome could not be analyzed because patients could not be reached to collect data at one month and up to 3 months following surgery.