Trial Outcomes & Findings for Effect of Low Dose Corticosteroids on Perioperative Markers of Thrombosis and Fibrinolysis in Total Knee Arthroplasty (NCT NCT01815918)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

60 participants

Primary outcome timeframe

Baseline and up to 4 hours following surgery

Results posted on

2022-04-14

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	30	30
Overall Study COMPLETED	12	11
Overall Study NOT COMPLETED	18	19

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Patient samples not analyzable	3	4
Overall Study Lack of Efficacy	15	15

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=12 Participants 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.	Treatment n=11 Participants 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.	Total n=23 Participants Total of all reporting groups
Age, Continuous	66 years STANDARD_DEVIATION 8 • n=5 Participants	68 years STANDARD_DEVIATION 6 • n=7 Participants	67 years STANDARD_DEVIATION 7 • n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	11 participants n=7 Participants	23 participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants 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.	Treatment n=11 Participants 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.
Prothrombin Fragment (PF1.2), a Marker of Thrombin Generation Baseline	263.6 pMol/L Standard Deviation 158.6	266.5 pMol/L Standard Deviation 146.9
Prothrombin Fragment (PF1.2), a Marker of Thrombin Generation 4s	935.8 pMol/L Standard Deviation 331.9	615.9 pMol/L Standard Deviation 357.7

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants 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.	Treatment n=11 Participants 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.
Plasmin-alpha-2-antiplasmin Complex (PAP), a Marker of Fibrinolysis Baseline	623.3 ug/L Standard Deviation 324.8	808.4 ug/L Standard Deviation 372.1
Plasmin-alpha-2-antiplasmin Complex (PAP), a Marker of Fibrinolysis 4 hs	1086.8 ug/L Standard Deviation 536.3	1638.6 ug/L Standard Deviation 823.2

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Treatment

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Kethy Jules-Elysee, MD

Hospital for Special Surgery

Phone: 212-606-1206

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place