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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

Tracking Information
First Submitted Date  ICMJE June 25, 2019
First Posted Date  ICMJE September 9, 2019
Last Update Posted Date November 22, 2019
Actual Study Start Date  ICMJE July 24, 2019
Estimated Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 6, 2019)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04082533 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2019)
  • 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.
  • 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).
  • 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).
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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)
  • 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.
  • Biomechanical findings [ Time Frame: preoperative, 6 weeks, 1 year ]
    Biomechanical findings as assessed by EOS® imaging (pre-op, 6 weeks, 1 year)
Original Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2019)
  • 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.
  • 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).
  • 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).
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • Inflammatory state (via protein, ribonucleic acid (RNA), cellular, and tissue level analyses [ Time Frame: Day of surgery (intraoperative), postoperative day 1, postoperative week 6 (±2 weeks) ]
    Day of surgery (intra-operative), POD 1 , and postoperative week 6 (±2 weeks) inflammatory state (via protein, ribonucleic acid (RNA), cellular, and tissue level analyses)
  • 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.
  • Biomechanical findings [ Time Frame: preoperative, 6 weeks, 1 year ]
    Biomechanical findings as assessed by EOS® imaging (pre-op, 6 weeks, 1 year)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intravenous (IV) Hydrocortisone for TKA (Total Knee Arthroplasty)
Official Title  ICMJE Effect of Intravenous Hydrocortisone on Range of Motion After Total Knee Arthroplasty: A Randomized Placebo-Controlled Trial With Nested Case-Control Study
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Pain
  • Arthrofibrosis
  • Osteoarthritis, Knee
Intervention  ICMJE
  • 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.
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Hydrocortisone
  • 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.
    Intervention: Drug: Dextrose 5% in water (D5W)
  • 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.
    Intervention: Drug: Hydrocortisone
  • 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.
    Intervention: Drug: Dextrose 5% in water (D5W)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 6, 2019)
132
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 1, 2023
Estimated Primary Completion Date July 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 83 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: George Birch, BS (212)774-7377 birchg@hss.edu
Contact: Alexandra Sideris, PhD (212)774-2602
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04082533
Other Study ID Numbers  ICMJE 2018-0660
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
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
Supporting Materials: 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.
Responsible Party Hospital for Special Surgery, New York
Study Sponsor  ICMJE Hospital for Special Surgery, New York
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Hospital for Special Surgery, New York
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP