Clinical trial NCT04082533: Intravenous (IV) Hydrocortisone for TKA (Total Knee Arthroplasty)
Official title: Effect of Intravenous Hydrocortisone on Range of Motion After Total Knee Arthroplasty: A Randomized Placebo-Controlled Trial With Nested Case-Control Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Pain
Arthrofibrosis
Osteoarthritis, Knee
Keywords: total knee replacement
hydrocortisone
Lead sponsor: Hospital for Special Surgery, New York
Sponsor class: OTHER
First posted: 2019-09-09
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Maximum age (years): 83
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: Postoperative Range of Motion (ROM)
timeFrame: 6 weeks postoperative (±2 weeks)
Secondary outcomes:
measure: Postoperative Stiffness
timeFrame: 6 weeks postoperative (±2 weeks)
measure: Numeric Rating Scale (NRS)
timeFrame: baseline (preoperative), postoperative day (POD) 1, POD2, 6 weeks postop, 1 year postop, 2 years postop
measure: PainDETECT Neuropathic Pain Score
timeFrame: baseline (preoperative), 6 weeks postop, 1 year postop, 2 years postop
measure: Opioid consumption
timeFrame: pre-surgical screening (PSS and holding area), day of surgery (DOS), POD1, POD2 at 6 weeks, 6 months 1 year and 2 years postoperatively,
measure: Knee injury and Osteoarthritis Outcome Score (KOOS Jr.)
timeFrame: Preoperative, 6 weeks, 6 months, 1 year, 2 years postoperative
measure: Lower extremity Activity Survey (LEAS) scores
timeFrame: preoperative, 6 weeks, 6 months, 1 year, 2 years postoperative
measure: Veterans Rand 12-item health survey (VR-12) score
timeFrame: preoperative, 6 weeks, 6 months, 1 year, 2 years postoperative
measure: TIme to physical therapy goals completion
timeFrame: postoperative day 0-3
measure: Inflammatory state (via protein, ribonucleic acid (RNA), cellular, and tissue level analyses
timeFrame: Day of surgery (preoperative), postoperative day 1, postoperative week 6 (±2 weeks)
measure: MRI Findings
timeFrame: preoperative, 1 year, 2 years
measure: Biomechanical findings
timeFrame: preoperative, 6 weeks, 1 year
Other outcomes:
Locations:
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
Study officials:
References: