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

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ClinicalTrials.gov Identifier: NCT04082533
Recruitment Status : Recruiting
First Posted : September 9, 2019
Last Update Posted : November 22, 2019
Sponsor:
Information provided by (Responsible Party):
Hospital for Special Surgery, New York

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Pain Arthrofibrosis Osteoarthritis, Knee Drug: Hydrocortisone Drug: Dextrose 5% in water (D5W) Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 132 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Intravenous Hydrocortisone on Range of Motion After Total Knee Arthroplasty: A Randomized Placebo-Controlled Trial With Nested Case-Control Study
Actual Study Start Date : July 24, 2019
Estimated Primary Completion Date : July 1, 2021
Estimated Study Completion Date : January 1, 2023


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 Name: 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 Name: Placebo




Primary Outcome Measures :
  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 Outcome Measures :
  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)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 83 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04082533


Contacts
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Contact: George Birch, BS (212)774-7377 birchg@hss.edu
Contact: Alexandra Sideris, PhD (212)774-2602

Locations
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United States, New York
Hospital for Special Surgery Recruiting
New York, New York, United States, 10021
Contact: George Birch, BS    212-773-7377    birchg@hss.edu   
Principal Investigator: Kethy M Jules-Elysee, MD         
Sponsors and Collaborators
Hospital for Special Surgery, New York

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Responsible Party: Hospital for Special Surgery, New York
ClinicalTrials.gov Identifier: NCT04082533     History of Changes
Other Study ID Numbers: 2018-0660
First Posted: September 9, 2019    Key Record Dates
Last Update Posted: November 22, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Supporting information will be made available when results are posted.
Access Criteria: Proposals should be directed to the Principal Investigator and may be submitted up to 36 months after article publication.

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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
Keywords provided by Hospital for Special Surgery, New York:
total knee replacement
hydrocortisone
Additional relevant MeSH terms:
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Osteoarthritis, Knee
Osteoarthritis
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Anti-Inflammatory Agents