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NCT Number: NCT04082533

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

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.

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This study is active but is not currently recruiting participants.

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Key information

Age range

18 year–83 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Hospital for Special Surgery

New York, 10021, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Hydrocortisone

Drug

Patients will be receiving 100 mg intravenous hydrocortisone every 8 hours, starting in the holding area roughly 2 hours prior to first incision.

Dextrose 5% in water (D5W)

Drug

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

Primary outcomes

  1. Postoperative Range of Motion (ROM)

    Time frame: 6 weeks postoperative (±2 weeks)

    The primary outcome is range of motion at patients' 6 week (±2 weeks) postoperative surgeon appointment.

Secondary outcomes

  1. Postoperative Stiffness

    Time frame: 6 weeks postoperative (±2 weeks)

    The rate of stiffness at the patients' 6 week postoperative surgeon appointment. Stiffness is defined as flexion < 100 degrees or extension lag > 10 degrees.

  2. Numeric Rating Scale (NRS)

    Time frame: baseline (preoperative), postoperative day (POD) 1, POD2, 6 weeks postop, 1 year postop, 2 years postop

    Patient reported pain level on a scale from 0 (no pain at all) to 10 (worst pain imaginable).

  3. PainDETECT Neuropathic Pain Score

    Time frame: baseline (preoperative), 6 weeks postop, 1 year postop, 2 years postop

    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).

  4. Opioid consumption

    Time frame: pre-surgical screening (PSS and holding area), day of surgery (DOS), POD1, POD2 at 6 weeks, 6 months 1 year and 2 years postoperatively,

    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

  5. Knee injury and Osteoarthritis Outcome Score (KOOS Jr.)

    Time frame: Preoperative, 6 weeks, 6 months, 1 year, 2 years postoperative

    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.

  6. Lower extremity Activity Survey (LEAS) scores

    Time frame: preoperative, 6 weeks, 6 months, 1 year, 2 years postoperative

    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.

  7. Veterans Rand 12-item health survey (VR-12) score

    Time frame: preoperative, 6 weeks, 6 months, 1 year, 2 years postoperative

    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.

  8. TIme to physical therapy goals completion

    Time frame: postoperative day 0-3

    Time to attainment of physical therapy (PT) goals (Ambulation 100 meters, independent transfer) measured during inpatient stay.

  9. Inflammatory state (via protein, ribonucleic acid (RNA), cellular, and tissue level analyses

    Time frame: Day of surgery (preoperative), postoperative day 1, postoperative week 6 (±2 weeks)

    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)

  10. MRI Findings

    Time frame: preoperative, 1 year, 2 years

    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.

  11. Biomechanical findings

    Time frame: preoperative, 6 weeks, 1 year

    Biomechanical findings as assessed by EOS® imaging (pre-op, 6 weeks, 1 year)

Sponsors and collaborators

Lead sponsor

Hospital for Special Surgery, New York

Other

Registry information

Official study title

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

Important dates

Study start
2019
Primary completion
2026
Study completion
2026
First posted
Sep 9, 2019
Registry last updated
Oct 6, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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