Yale Steroid Enhanced Versus Exparel Nerveblock TKA Part 2 (Yale SEVEN)

The objective of this study is to investigate the efficacy of Dexamethasone sodium phosphate plus Methylprednisolone acetate in combination with plain bupivacaine ((B-DEX-MPA) compared with Liposomal Bupivacaine in combination with plain bupivacaine (B-LB) on post-surgical pain control among patients undergoing bilateral 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.

Study Overview

• Status: Recruiting
• Conditions: Knee Arthroplasty; Total Knee Replacement
• Intervention / Treatment: Drug: Bupivacaine-Liposomal Bupivacaine; Drug: Bupivacaine -Dexamethasone Sodium Phosphate-Methylprednisolone Acetate

Detailed Description

This phase 2 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 bilateral total knee arthroplasty (TKA).

The primary objective of this 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 bilateral 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). An anticipated 66 participants who are scheduled for primary, elective bilateral TKA will be enrolled.

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jinlei Li, MD PhD; Phone Number: 475-434-4038; Email: jinlei.li@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale New Haven Hospital Saint Raphael Campus
      • Contact: Jinlei Li, MD PhD; Phone Number: 475-434-4038; Email: jinlei.li@yale.edu
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale New Haven Hospital York Street Campus
      • Contact: Jinlei Li, MD PhD; Phone Number: 475-434-4038; Email: jinlei.li@yale.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• American Society of Anesthesiologists status I, II and III, elective, primary, bilateral 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: B-LB in left knee and B-DEX-MPA in right knee; Participants in this arm will receive B-LB in their left knee and B-DEX-MPA in their right knee. Nerve block with (B-LB): A medication mixture of 40 ml (20 ml LB and 20 ml 0.25% plain bupivacaine) will be prepared, of which 20 ml will be used in Adductor canal block, 10 ml will be used in iPACK block and 5 ml each will be used in medial upper and lateral upper genicular nerve block, respectively. Nerve block with (B-DEX-MPA): A medication mixture of 40 ml (40 ml 0.25% plain bupivacaine, 10 mg DEX and 80 mg MPA) will be prepared, of which 20 ml will be used in Adductor canal block, 10 ml will be used in iPACK block and 5 ml each will be used in medial upper and lateral upper genicular nerve block, respectively.	Drug: Bupivacaine-Liposomal Bupivacaine; A medication mixture of 40 ml (20 ml LB and 20 ml 0.25% plain bupivacaine) will be prepared, of which 20 ml will be used in Adductor canal block, 10 ml will be used in iPACK block and 5 ml each will be used in medial upper and lateral upper genicular nerve block, respectively.; Other Names: B-LB; Drug: Bupivacaine -Dexamethasone Sodium Phosphate-Methylprednisolone Acetate; A medication mixture of 40 ml (40 ml 0.25% plain bupivacaine, 10 mg DEX and 80 mg MPA) will be prepared, of which 20 ml will be used in Adductor canal block, 10 ml will be used in iPACK block and 5 ml each will be used in medial upper and lateral upper genicular nerve block, respectively.; Other Names: B-DEX-MPA
Experimental: B-LB in right knee and B-DEX-MPA in left knee; Participants in this arm will receive B-LB in their right knee and B-DEX-MPA in their left knee. Nerve block with (B-LB): A medication mixture of 40 ml (20 ml LB and 20 ml 0.25% plain bupivacaine) will be prepared, of which 20 ml will be used in Adductor canal block, 10 ml will be used in iPACK block and 5 ml each will be used in medial upper and lateral upper genicular nerve block, respectively. Nerve block with (B-DEX-MPA): A medication mixture of 40 ml (40 ml 0.25% plain bupivacaine, 10 mg DEX and 80 mg MPA) will be prepared, of which 20 ml will be used in Adductor canal block, 10 ml will be used in iPACK block and 5 ml each will be used in medial upper and lateral upper genicular nerve block, respectively.	Drug: Bupivacaine-Liposomal Bupivacaine; A medication mixture of 40 ml (20 ml LB and 20 ml 0.25% plain bupivacaine) will be prepared, of which 20 ml will be used in Adductor canal block, 10 ml will be used in iPACK block and 5 ml each will be used in medial upper and lateral upper genicular nerve block, respectively.; Other Names: B-LB; Drug: Bupivacaine -Dexamethasone Sodium Phosphate-Methylprednisolone Acetate; A medication mixture of 40 ml (40 ml 0.25% plain bupivacaine, 10 mg DEX and 80 mg MPA) will be prepared, of which 20 ml will be used in Adductor canal block, 10 ml will be used in iPACK block and 5 ml each will be used in medial upper and lateral upper genicular nerve block, respectively.; Other Names: B-DEX-MPA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Change in 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Average Postoperative Knee Pain Score	Average postoperative knee pain scores for each surgical knee 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 each surgical knee 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
Prosthetic joint range of motion	Compare prosthetic joint range of motion for each surgical knee 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

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Department of Anesthesiology Faculty Development Fund
• Investigators: Principal Investigator: Jinlei Li, MD PhD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: February 17, 2023
• First Posted (Actual): February 21, 2023

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Sensory System Agents; Anesthetics; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Neuroprotective Agents; Protective Agents; Anesthetics, Local; Dexamethasone; Dexamethasone acetate; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; BB 1101; Bupivacaine; Dexamethasone 21-phosphate
• Other Study ID Numbers: 2000031881_a

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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