Intravenous (IV) Hydrocortisone for TKA (Total Knee Arthroplasty)

Effect of Intravenous Hydrocortisone on Range of Motion After Total Knee Arthroplasty: A Randomized Placebo-Controlled Trial With Nested Case-Control Study

In this study, total knee replacement patients will be determined to be stiff or non-stiff preoperatively. Stiffness designation is determined by preoperative range of motion (if flexion is < 100 degrees, or extension lag is > 10 degrees). The stiff and non-stiff groups will both be randomized to two groups to receive either intravenous hydrocortisone or a placebo at 3 intervals postoperatively. Patients will be followed up with in hospital and via the phone on postoperative day (POD) 1 and 2, as well as 6 weeks, 6 months, 1 year, and 2 years postoperatively. Patients will also have blood drawn preoperatively in the OR, on POD1, at their 6 week followup, and at their 1 and 2 year follow ups. This blood will be processed and analyzed.

Study Overview

• Status: Active, not recruiting
• Conditions: Pain; Osteoarthritis, Knee; Arthrofibrosis
• Intervention / Treatment: Drug: Hydrocortisone; Drug: Dextrose 5% in water (D5W)

Detailed Description

TKA is the standard of care for treating patients suffering from end-stage knee arthritis and other disabling knee injuries. Indications have increased to ever younger patients and, combined with the aging US population, nearly 700,000 Americans receive TKAs each year. In spite of surgery, many patients experience persistent pain, stiffness or instability that negatively impacts their quality of life; up to 5% experience TKA failure in the first 10 years.

Presently, IV stress dose steroids is an accepted practice for bilateral knee replacement (BTKR) leading to decreased pain 24 hours after surgery and improved range of motion (ROM) on postoperative day 2 (POD2). These benefits are likely due to suppression of inflammation immediately after surgery. It is not clear if IV stress dose steroids improve ROM at later time points. Moreover, it is not clear if IV hydrocortisone improves clinical outcomes in unilateral TKA, where pain and joint stiffness remain significant challenges weeks after surgery. The investigators hypothesize that IV hydrocortisone will increase ROM at 6 weeks following surgery.

This study will enroll 132 patients that will be followed for up to 2 years. By integrating cell and molecular biology, biomechanics, and imaging technologies (including a CT scan at 1 year), this study is designed to comprehensively examine the long term effects of IV hydrocortisone on joint stiffness, pain, clinically relevant inflammatory states, and the synovium following unilateral TKA. Because subjects with variable ROMs will be enrolled in the study and followed over time, the findings may enable the development of biomarker prediction tools and the targeting of appropriate prevention and management measures for patients at highest risk of joint stiffness and subsequent surgical intervention.

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Hospital For Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Elective primary unilateral total knee arthroplasty
• Osteoarthritis (OA) within the affected joint
• Patients of surgeons who have agreed to participate in the study
• Age ≥18 to 83 years
• American Society of Anesthesiologists (ASA) Physical Status 1-3
• Neuraxial Anesthesia
• Adductor canal block (ACB), Interspace between the popliteal artery and capsule of the posterior knee (IPACK) block (unless valgus knee patient), and Periarticular Injection (PAI) for postoperative pain

Exclusion Criteria:

• Contraindication to regional anesthesia, non-steroidal anti-inflammatory drugs, or steroids
• Pre-operative oral steroid use in the past 3 months
• Body mass index (BMI) greater than or equal to 45
• Intraarticular steroid injections within two months of scheduled surgery in affected joint
• Non-English speaking
• Pre-existing diagnosis of rheumatic disease, autoimmune disease, or immunodeficiency (e.g. rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, multiple sclerosis, Type I diabetes)
• Active infection
• History of >6 weeks of daily opioid use and/or any use of non-prescribed opioids within one year
• Pregnant women
• Previous study participants in this study
• Type II Diabetes on insulin
• History of refractory postoperative nausea and vomiting (PONV) or PONV after sedation (can include if nausea only after general anesthesia)
• Previous hardware in affected joint
• Open Reduction and Internal Fixation (ORIF) surgery to affected joint
• Cementless total knee arthroplasty (TKA)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Stiffness Intravenous Hydrocortisone; Total knee replacement patients with preoperative knee stiffness (defined as flexion < 100 degrees or extension lag > 10 degrees) receive 3 doses of 100mg intravenous hydrocortisone every 8 hours. The first dose is given in the holding area approximately 2 hours prior to first incision.	Drug: Hydrocortisone; Patients will be receiving 100 mg intravenous hydrocortisone every 8 hours, starting in the holding area roughly 2 hours prior to first incision.
Placebo Comparator: Stiffness Intravenous Placebo; Total knee replacement patients with preoperative knee stiffness (defined as flexion < 100 degrees or extension lag > 10 degrees) receive 3 doses of matched volume diluent every 8 hours. The first dose is given in the holding area approximately 2 hours prior to first incision.	Drug: Dextrose 5% in water (D5W); Patients will be receiving a matched volume of D5W every 8 hours, starting in the holding area roughly 2 hours prior to first incision.; Other Names: Placebo
Active Comparator: Non-stiff Intravenous Hydrocortisone; Total knee replacement patients without preoperative knee stiffness (defined as flexion < 100 degrees or extension lag > 10 degrees) receive 3 doses of 100mg intravenous hydrocortisone every 8 hours. The first dose is given in the holding area approximately 2 hours prior to first incision.	Drug: Hydrocortisone; Patients will be receiving 100 mg intravenous hydrocortisone every 8 hours, starting in the holding area roughly 2 hours prior to first incision.
Placebo Comparator: Non-stiff Intravenous placebo; Total knee replacement patients without preoperative knee stiffness (defined as flexion < 100 degrees or extension lag > 10 degrees) receive 3 doses of matched volume diluent every 8 hours. The first dose is given in the holding area approximately 2 hours prior to first incision.	Drug: Dextrose 5% in water (D5W); Patients will be receiving a matched volume of D5W every 8 hours, starting in the holding area roughly 2 hours prior to first incision.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Range of Motion (ROM)	The primary outcome is range of motion at patients' 6 week (±2 weeks) postoperative surgeon appointment.	6 weeks postoperative (±2 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Stiffness	The rate of stiffness at the patients' 6 week postoperative surgeon appointment. Stiffness is defined as flexion < 100 degrees or extension lag > 10 degrees.	6 weeks postoperative (±2 weeks)
Numeric Rating Scale (NRS)	Patient reported pain level on a scale from 0 (no pain at all) to 10 (worst pain imaginable).	baseline (preoperative), postoperative day (POD) 1, POD2, 6 weeks postop, 1 year postop, 2 years postop
PainDETECT Neuropathic Pain Score	Patient reported PainDETECT neuropathic pain scores. Scores from 0-12 indicate no neuropathic pain, 13-18 indicates unclear neuropathic pain, 19-38 indicates positive neuropathic pain. The PainDETECT questionnaire asks numerous questions regarding the type of pain patients are experiencing and answers are scored never (0), hardly noticed (1), slightly (2), moderately (3), strongly (4), and very strongly (5).	baseline (preoperative), 6 weeks postop, 1 year postop, 2 years postop
Opioid consumption	Patient reported opioid consumption information at pre-surgical screening appointment, in the holding area before surgery, on postoperative day 1, postoperative day 2, 6 weeks, 6 months, 1 year and 2 years postoperatively	pre-surgical screening (PSS and holding area), day of surgery (DOS), POD1, POD2 at 6 weeks, 6 months 1 year and 2 years postoperatively,
Knee injury and Osteoarthritis Outcome Score (KOOS Jr.)	Knee injury and Osteoarthritis Outcome Score (KOOS Jr.) scores measured at baseline, 6 weeks, 6 months and 1 year and 2 years postoperatively. The KOOS Jr. survey involves 7 questions scored from 0 to 4 for a total score of 0 to 28. A score of 0 correlates to complete loss of knee function, whereas 28 correlates to completely healthy knee function.	Preoperative, 6 weeks, 6 months, 1 year, 2 years postoperative
Lower extremity Activity Survey (LEAS) scores	Lower extremity Activity Survey (LEAS) scores at baseline, 6 weeks, 6 months and 1 year and 2 years postoperatively. The LEAS contains 20 questions regarding a person's ability to perform everyday function. Each question is scored from 0-4. A score of 0 correlates to no function and complete inability to perform every day tasks to 80 correlating to normal function.	preoperative, 6 weeks, 6 months, 1 year, 2 years postoperative
Veterans Rand 12-item health survey (VR-12) score	The Veterans Rand 12-item health survey (VR-12) scores at baseline, 6 weeks, 6 months and 1 year and 2 years postoperatively. The VR-12 questionnaire is a series of 12 questions that evaluate a patient's physical and emotional health status. It is scored from 0 to 50, with 50 correlating to healthy mental and physical status.	preoperative, 6 weeks, 6 months, 1 year, 2 years postoperative
TIme to physical therapy goals completion	Time to attainment of physical therapy (PT) goals (Ambulation 100 meters, independent transfer) measured during inpatient stay.	postoperative day 0-3
Inflammatory state (via protein, ribonucleic acid (RNA), cellular, and tissue level analyses	Day of surgery (pre-operative), POD 1 , and postoperative week 6 (±2 weeks) inflammatory state (via protein, ribonucleic acid (RNA), cellular, and tissue level analyses)	Day of surgery (preoperative), postoperative day 1, postoperative week 6 (±2 weeks)
MRI Findings	MRI Findings (pre-operative, 1 yr, 2yr ). MRIs of the knee will be reviewed by the radiology department and their findings and changes noted and logged.	preoperative, 1 year, 2 years
Biomechanical findings	Biomechanical findings as assessed by EOS® imaging (pre-op, 6 weeks, 1 year)	preoperative, 6 weeks, 1 year

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2019
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: June 25, 2019
• First Submitted That Met QC Criteria: September 6, 2019
• First Posted (Actual): September 9, 2019

Study Record Updates

• Last Update Posted (Estimated): October 6, 2025
• Last Update Submitted That Met QC Criteria: October 1, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: total knee replacement; hydrocortisone
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Osteoarthritis, Knee; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Carbohydrates; Polycyclic Compounds; Inorganic Chemicals; Pregnanes; Steroids; Fused-Ring Compounds; Anions; Ions; Electrolytes; Hydroxides; Alkalies; Oxides; Oxygen Compounds; Pregnenediones; Pregnenes; Sugars; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; 17-Hydroxycorticosteroids; Hexoses; Monosaccharides; Hydrocortisone; Water; Glucose
• Other Study ID Numbers: 2018-0660

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the primary outcome beginning 9 months and following 36 months after article publication. These data may be shared with investigators whose proposed use of data have been approved by an independent review committee for the purposes of a meta-analysis.
• IPD Sharing Time Frame: Supporting information will be made available when results are posted.
• IPD Sharing Access Criteria: Proposals should be directed to the Principal Investigator and may be submitted up to 36 months after article publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No