Yale Steroid Enhanced Versus Exparel Nerveblock TKA RCT Study

Study Overview
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Brief Summary
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The objective of this phase 2 study is to investigate the efficacy of Dexamethasone sodium phosphate (DEX) plus Methylprednisolone acetate (MPA) in combination with plain bupivacaine (B) compared with Liposomal Bupivacaine (LB) in combination with plain bupivacaine on post-surgical pain control among patients undergoing unilateral total knee arthroplasty (TKA) to asses if perineural B-DEX-MPA will result in superior analgesia efficacy as compared to B-LB. This study will also assess if perineural B-DEX-MPA results in improved quality of postoperative recovery as compared to B-LB.

Detailed Description
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This phase 2, double blinded and randomized clinical trial will investigate the efficacy of Dexamethasone sodium phosphate (DEX) plus Methylprednisolone acetate (MPA) in combination with plain bupivacaine (B) compared with Liposomal Bupivacaine (LB) in combination with plain bupivacaine on post-surgical pain control among patients undergoing unilateral total knee arthroplasty (TKA). The primary objective of this phase 2 study is to investigate the efficacy of Dexamethasone sodium phosphate (DEX) plus Methylprednisolone acetate (MPA) in combination with plain bupivacaine (B) compared with Liposomal Bupivacaine (LB) in combination with plain bupivacaine on post-surgical pain control among patients undergoing total knee arthroplasty (TKA). The secondary objective of this study is to test the effects of perineural use of B-DEX-MPA vs B-LB on the quality of postoperative recovery as well as surgical outcome and neuropathic pain among patients undergoing unilateral TKA. This study will also assess if perineural B-DEX-MPA results in improved quality of postoperative recovery as compared to B-LB. This will be a single center study at Yale New Haven Hospital (YNHH) performed at two clinical sites: York St. Campus (York Street, New Haven) and St. Raphael Campus (Chapel Street, New Haven). 250 primary, elective and unilateral TKA patients will be enrolled, and equally randomized (1:1 ratio) to receive peripheral nerve blockade with B- LB or B-DEX-MPA.

Official Title
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Yale Steroid Enhanced Versus Exparel Nerveblock TKA Randomized Controlled Trial (RCT) Study

Conditions
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Total Knee Replacement, Knee Arthroplasty

Intervention / Treatment
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* Drug: Bupivacaine-Liposomal Bupivacaine
* Drug: Bupivacaine -Dexamethasone Sodium Phosphate-Methylprednisolone Acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society of Anesthesiologists status I, II and III, elective, primary, unilateral TKA planned for spinal anesthesia with plain 0.5% bupivacaine. Exclusion Criteria: Refusal of consent Pregnancy Conditions making the patient unable to fill out questionnaire online, through email or over the phone including with cognitive dysfunction, psychiatric disorder, or non-English speaking patients, or lack of internet access which would prevent post discharge follow-up electronically Coagulopathy Allergy to or for any other reasons cannot use Acetaminophen, Celebrex, local anesthetic bupivacaine, DEX, MPA or LB Patients on any amounts of opioids within one month of the surgery date, any substance abuse such as regular marijuana user (more frequent than once per month) Insulin dependent or uncontrolled diabetes defined as, day of surgery finger stick glucose >200mg/dl, or HbA1C > 8.0% Peripheral Nerve Block site or systemic infection Immune compromise (e.g., HIV, chronic glucocorticoid use) Severe pre-existing neuropathy TKA for indications other than osteoarthritis such as post-traumatic injury or rheumatoid arthritis, history of surgery in the ipsilateral knee joint, revision TKA or bilateral TKA Severe hepatic or renal dysfunction (GFR <50 ml/min) Actual body weight <60 kg Patients with active or latent peptic ulcers, diverticulitis, fresh intestinal anastomoses, and non-specific ulcerative colitis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bupivacaine-Liposomal Bupivacaine (B-LB)<br>Nerve blockade administration will be carried out per standard of care. All patients will receive single injection under ultrasound guidance with adductor canal block comprised of 20 ml 0.25% plain bupivacaine + 10 ml LB (133 mg) with the total volume of 30 ml; 10 ml 0.25% plain bupivacaine + 10 ml LB (133 mg) with the total volume of 20 ml will be administered through an Interspace between the popliteal artery and capsule of the posterior knee (iPACK) block. | Drug: Bupivacaine-Liposomal Bupivacaine<br>* Adductor canal block comprised of 20 ml 0.25% plain bupivacaine + 10 ml LB (133 mg) with the total volume of 30 ml; 10 ml 0.25% plain bupivacaine + 10 ml LB (133 mg) with the total volume of 20 ml will be administered through an iPACK block<br>|
| Experimental: Bupivacaine -Dexamethasone Sodium Phosphate-Methylprednisolone Acetate (B-DEX-MPA)<br>Nerve blockade administration will be carried out per standard of care. All patients will receive single injection under ultrasound guidance with adductor canal block comprised of 30 ml 0.25% plain bupivacaine + 5 mg DEX (0.5 ml) and 40 mg MPA (1 ml); 20 ml 0.25% plain bupivacaine + 5 mg DEX (0.5 ml) and 40 mg MPA (1 ml) will be administered through an iPACK block. | Drug: Bupivacaine -Dexamethasone Sodium Phosphate-Methylprednisolone Acetate<br>* Adductor canal block comprised of 30 ml 0.25% plain bupivacaine + 5 mg DEX (0.5 ml) and 40 mg MPA (1 ml); 20 ml 0.25% plain bupivacaine + 5 mg DEX (0.5 ml) and 40 mg MPA (1 ml) will be administered through an iPACK block.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative Knee Pain Score | Average postoperative knee pain scores for the first two postoperative days using Visual analogue scale (VAS) pain score. Score range from 0 (no pain) to 10 (worst pain possible). | Day 1 and Day 2 | 
| Postoperative opioid consumption | In-hospital postoperative opioid consumption in oral milligram morphine equivalent (OME) will be monitored up to 48-hour between anesthesia end time and discharge time | From anesthesia end time to discharge time, up to 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Postoperative Knee Pain Score | Average postoperative knee pain scores for postoperative day 7 using Visual analogue scale (VAS) pain score. Score range from 0 (no pain) to 10 (worst pain possible). | Day 7 | 
| Worst and best pain score | Worst and best postoperative knee pain scores for days 1, 2 and 7 using Visual analogue scale (VAS) pain score. Score range from 0 (no pain) to 10 (worst pain possible). | Day 1, Day 2 and Day 7 | 
| Change in functional pain using Brief Pain Inventory (BPI) | Compare functional pain using the BPI at baseline, 6 weeks and 3 months. The BPI scale defines pain as follows: Score: 1 - 4 = Mild Pain, Score: 5 - 6 = Moderate Pain, Score: 7 - 10 = Severe Pain. | baseline, 6 weeks and 3 months | 
| Change in neuropathic pain using PainDetect | Compare neuropathic pain at baseline, 6 weeks and 3 months using PainDetect: a nine-item questionnaire that consists of seven sensory symptom items for pain that are graded from 0= never to 5= strongly, one temporal item on pain-course pattern graded -1 to +1, and one spatial item on pain radiation graded 0 for no radiation or +2 for radiating pain. | baseline, 6 weeks and 3 months | 
| Persistent opioid use using Yale Postoperative Recovery Scale | Persistent opioid use will be compared using the Yale Postoperative Recovery Scale on postoperative day 7, 6 weeks and 3 months. It is comprised of 3 free-text questions: Is patient still taking opioid medications, Yes or No; The number of pills left in pill box;and Has the patient needed a prescription refill, Yes or No. | Day 7, 6 weeks and 3 months | 
| Persistent opioid use using NarX | Persistent opioid use will be compared using the NarX score at 6 weeks and 3 months, scores range from 000-999; higher scores indicate more opioid usage | 6 weeks and 3 months | 
| Change in Quality of Recovery 40 questionnaire | 40 questions assessing quality of recovery graded on a five-point Likert scale, total score range from 40 (extremely poor recovery) to 200 (excellent recovery) | Day 1, 2 and 7 | 
| Prosthetic joint range of motion | Compare prosthetic joint range of motion using the patient's electronic medical record as reported by the physical therapist at baseline, day 0, day 1, and day 2 | baseline, day 0, day 1 and day 2 | 
| Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Global-10 | The PROMIS Global-10 is a 10-item patient-reported questionnaire that measures changes in general health in which the response options are presented as 5-point scale, 5 (without any difficulty) to 1 (Unable to do). Higher scores indicate a healthier patient. | 6 weeks and 3 months | 
| Change in knee functional status using Knee injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR) | Compare knee functional status using KOOS JR at 6 weeks and 3 months after surgery, Scores range from 0 to 100 with a score of 0 indicating total knee disability and 100 indicating perfect knee health. | 6 weeks and 3 months | 
| Length of stay | The patient's post surgical length of stay in the hospital will be compared between treatment groups. | from the start of the surgery to discharge from hospital, up to 48 hours | 
| Change in glucose | Compare the change in postoperative serum glucose from baseline. | baseline, day 0, day 1 and day 2 | 
| Change in white blood cell count (WBC) | Compare the change in postoperative WBC from baseline. | baseline, day 0, day 1 and day 2 | 
| Absolute value of Interleukin 1 beta (IL-1b) | Absolute value IL-1b at postoperative day 1 | day 1 |