The Effect of Regional Anesthesia and Periarticular Injection and Versus Periarticular Injection Alone on Early Recovery After Total Knee Arthroplasty: A Prospective Randomized Trial
Phase: PHASE4
Conditions: Pain, Postoperative
Sponsor: Washington University School of Medicine

 
 
 
 
The Effect of Regional Anesthesia and Periarticular Injection and Versus Periarticular 
Injection Alone on Early Recovery after Total Knee Arthroplasty: A Prospective 
Randomized Trial 
 
NCT06410612   Unique Protocol ID: 202311211 
  
Date:2/29/24 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

The Effect of Regional Anesthesia and Periarticular Injection and Versus Periarticular 
Injection Alone on Early Recovery after Total Knee Arthroplasty: A Prospective 
Randomized Trial 
 
 
 
 
Main Sites: Barnes-Jewish West County Hospital  
Study Coordinator: Venessa Riegler 
 
PI: Andrew Schneider 
 
Participating surgeons: Andrew Schneider, Robert Barrack 
 
Purpose 
The purpose of the study is to compare two types of perioperative analgesic modalities, adductor 
canal block plus interspace between popliteal artery and capsule of the knee (IPACK) block and 
periarticular injection versus periarticular injection alone, to determine their relative efficacies 
with regard to pain relief and functional outcomes in the early postoperative period following 
primary total knee arthroplasty.   
 
Hypothesis 
We hypothesize that periarticular injection alone will be non-inferior in terms of pain scores, 
opioid consumption, and objective functional recovery metrics compared to periarticular 
injections with the addition of regional anesthesia (adductor canal block plus IPACK block.  
 
Background  
The widespread adoption of multimodal analgesia in contemporary total knee arthroplasty 
(TKA) has led to improvements in perioperative pain control, expedited recovery times, and 
shorter hospital stays1–3. Periarticular injections (PAIs), adductor canal blocks (ACBs), and 
interspace between popliteal artery and capsule of the knee (IPACK) blocks are commonly 
utilized as part of contemporary multimodal analgesia protocols, but their relative efficacies in 
improving early recovery after TKA has yet to be definitively elucidated4. There are a few 
known potential drawbacks of ACBs and IPACKs including surgical delay due to administration 
timing, increased costs, and small risks associated with a regional block. Both regional 
anesthesia and PAI have been found to be effective alone in improving pain and opioid 
consumption, but there is limited data on whether there is an additive benefit of providing both 
treatments for patients undergoing primary TKA. Therefore, the purpose of our study is to 
compare the efficacy of regional anesthesia and PAI vs. PAI alone for pain management and 
functional recovery in the early postoperative period following TKA. 
 
Design 
Prospective randomized trial  
 
Treatment Groups 

All ACBs will be administered as a single shot preoperatively in the holding area on the day of 
surgery by the regional anesthesia team and PAIs will be administered intraoperatively by the 
treating orthopaedic surgeon. 
 
Group 1: regional anesthesia (ACB + IPACK) and PAI 
Group 2: PAI alone 
 
Inclusion Criteria 
Age > 18 years  
Primary unilateral total knee arthroplasty  
BMI<45 
Primary diagnosis of osteoarthritis 
Patient owns smartphone capable of running the patient engagement platform and wearable 
activity monitor 
Robotic-assisted surgery 
 
Exclusion Criteria 
Preexisting functionally limiting neurologic disorders 
hepatic or renal insufficiency 
history of unprovoked venous thromboembolism 
Inability to complete baseline functional testing 
Chronic opioid or gabapentin and pregabalin use (chronic defined as use >5 days per week prior 
to the surgical procedure) 
Allergy or intolerance to trial medications 
Planned admission to a postoperative rehabilitation facility 
Planned general anesthesia 
Receiving Workers’ Compensation or disability payments 
 
Primary Outcome 
Mean VAS pain score for 2 weeks postoperatively 
 
Secondary Outcomes 
Daily opioid consumption 
Daily VAS score at rest  
Daily step count during the first 14 days postoperatively 
Length of stay 
Complications 
Knee range of motion  
Oxford Knee Score 
Sleep quality  
 
Power Analysis 
A prior study by Grosso et al. identified a VAS pain score with ACB alone to have an average of 
3.8 (standard deviation of 2.7) over the first 3 post-operative days2. Moreover, they identified a 
mean VAS pain score of 2.75 (standard deviation of 2.3) among those receiving an ACB and 
PAI over the first 3 post operative days. Assuming a common within-group assessment in the 

proposed study, the Cohen's d effect size of 0.42 was calculated for use in an a priori power 
analysis. With a power of 80% at a 2-sided alpha of 0.05 and 1:1 allocation, a power analysis 
resulted in 90 subjects required for each arm of the study (180 subjects total). Accounting for 
unknown contributing factors that may lead to exclusion of patients from the study, 200 subjects 
(100 in each arm) will be enrolled in this trial. We will plan to do a midterm analysis once 100 
patients have been enrolled.  
 
Methodology 
Randomization and Interventions 
Patients will be randomized to receive a PAI with or without regional anesthesia using a 
computerized formal probability model with block design and 1:1 allocation ratio. This will 
occur in the clinic when the patient is indicated for surgery. Only those patients that are 
randomized to the regional anesthesia group will be billed for regional anesthesia. Regional 
anesthesia will be administered by an anesthesiologist and staff working under his/her 
supervision using standard of care techniques. All patients will be issued and trained on a patient 
engagement platform (PEP) (FocusMotion, Santa Monica, CA) and a wearable activity monitor 
(FitBit Inspire HR, FitBit, San Francisco) at study recruitment5,6. The wearable activity monitor 
will be provided free of charge to the patients.  
 
. The periarticular injections will be given by the surgeon intraoperatively using standard of care 
techniques.  
 
Data Collection 
Patients will be instructed to begin using the PEP and wearable activity monitor 2 weeks before 
surgery for baseline data collection and continue use for 14 days postoperatively.  Patient 
reported outcome measures including the Oxford Knee Score (OKS) and Forgotten Joint Score 
(FJS), will be collected preoperatively via the PEP. Intraoperative and in-hospital data will be 
collected prospectively by surgeons and nursing staff. Mean running averages for daily VAS 
pain scores and opioid consumption as measured by morphine milligram equivalent (MME) will 
be calculated. Fourteen days of postoperative biometric data collected from the wearable activity 
monitor will include sleep duration, sleep quality, sleep disturbances, step count, as well as 
maximum resting heart rate. 
 
Enrollment 
We are planning for 1 enrolling site, Barnes Jewish West County Hospital.  
 
Risks, Benefits 
Total knee arthroplasty patients are routinely given PAI with or without the addition of regional 
anesthesia as standard of care; this decision is primarily based upon surgeon preference. 
Therefore, participation in this study does not involve any additional risk. However, whether the 
addition of regional anesthesia provides a clear clinical benefit is unknown, and thus there is no 
true standard for this important aspect of patient care.  There are known risks related to both 
local blocks alone as well as local blocks with the addition of a regional blocks, but the benefits 
of pain control, reduced opioid consumption, and enhanced functional recovery are believed to 
outweigh these risks.  
 

Breach of confidentiality and/or privacy is a risk of the study. Below is a description of the 
procedure for maintaining confidentiality. There is no direct benefit to the participants in this 
study.  
 
Procedures for Maintaining Confidentiality  
A breach of confidentiality and/or privacy is a risk of this study. To prevent this and protect 
patient identity and information, all collected data will be deidentified and stored electronically 
in password-protected files. All information will be collected and reviewed by the research team 
only. Data will be maintained on a password-protected computer. 
 
 
References 
1. Goytizolo EA, Lin Y, Kim DH, et al. Addition of Adductor Canal Block to Periarticular 
Injection for Total Knee Replacement: A Randomized Trial. The Journal of Bone and Joint 
Surgery. 2019;101(9):812-820. doi:10.2106/JBJS.18.00195 
2. Grosso MJ, Murtaugh T, Lakra A, et al. Adductor Canal Block Compared with Periarticular 
Bupivacaine Injection for Total Knee Arthroplasty: A Prospective Randomized Trial. The 
Journal of Bone and Joint Surgery. 2018;100(13):1141-1146. doi:10.2106/JBJS.17.01177 
3. Danoff JR, Goel R, Sutton R, Maltenfort MG, Austin MS. How Much Pain Is Significant? 
Defining the Minimal Clinically Important Difference for the Visual Analog Scale for Pain 
After Total Joint Arthroplasty. J Arthroplasty. 2018;33(7S):S71-S75.e2. 
doi:10.1016/j.arth.2018.02.029 
4. Hagar AD, Fang CJ, Dannenbaum JH, Smith EL, Bono JV, Talmo CT. Reducing Narcotic 
Usage With 0.5% Bupivacaine Periarticular Injections in Total Knee Arthroplasty. The 
Journal of Arthroplasty. 2022;37(5):851-856. doi:10.1016/j.arth.2022.01.026 
5. Lawrie CM, Hannon CP, Jo S, et al. Chitranjan S. Ranawat Award: Tourniquet Use Does Not 
Impact Trajectory of Total Knee Arthroplasty Early Recovery: A Prospective, Randomized 
Controlled Trial. The Journal of Arthroplasty. 2023;38(6):S7-S13. 
doi:10.1016/j.arth.2023.03.081 
6. Booth MW, Riegler V, King JS, Barrack RL, Hannon CP. Patients’ Perceptions of Remote 
Monitoring and App-Based Rehabilitation Programs: A Comparison of Total Hip and Knee 
Arthroplasty. The Journal of Arthroplasty. 2023;38(7):S39-S43. 
doi:10.1016/j.arth.2023.04.032