A Randomized Controlled Trial of Ultrasound Guided Knee Genicular Nerve Block and Anterior Femoral Cutaneous Nerve Block for Primary Total Knee Arthroplasty
Phase: PHASE4
Conditions: Total Knee Replacement, Genicular Nerve Block, Opioid Use
Sponsor: Hospital for Special Surgery, New York

Confidential 
Page 1 of 12 
 
 
 
 
 
 
 
 
 
A Randomized Controlled Trial of Ultrasound Guided Knee Genicular Nerve 
Block and Anterior Femoral Cutaneous Nerve Block for Primary Total Knee 
Arthroplasty 
FUNDER: Anesthesiology Research Department 
PROTOCOL NO.: 2023-0063 
VERSION & DATE: Version 1, 5/23/2023 
 
 
 
 
 
 
 
 
 
 
 
 
This document contains the confidential information of the Hospital for Special Surgery.  It is provided 
to you and your company’s personnel for review.  Your acceptance of this document constitutes an 
agreement that you will not disclose the information contained herein to others without the prior written 
consent of the Hospital for Special Surgery.  No other use or reproduction is authorized by Hospital for 
Special Surgery, nor does the Hospital for Special Surgery assume any responsibility for unauthorized 
use of this protocol. 

 
Protocol Number: 2023-0063  
Version Date: 5/23/2023  
 
Confidential 
Page 2 of 12 
 
 
 
TABLE OF CONTENTS 
TABLE OF CONTENTS ............................................ 2 
PROTOCOL SYNOPSIS ........................................... 4 
1.0 
INTRODUCTION ............................................. 6 
2.0 
OBJECTIVE OF CLINICAL STUDY ............... 6 
3.0 
STUDY HYPOTHESES .................................. 6 
4.0 
STUDY DESIGN ............................................. 6 
4.1 
Study Duration ................................................................................................................ 6 
4.2 
Endpoints ....................................................................................................................... 6 
4.2.1 
Primary Endpoint ...................................................................................................... 6 
4.2.2 
Secondary Endpoints ................................................................................................ 7 
4.3 
Study Sites ..................................................................................................................... 7 
5.0 
STUDY POPULATION ................................... 7 
5.1 
Number of Subjects ........................................................................................................ 7 
5.2 
Inclusion Criteria............................................................................................................. 7 
5.3 
Exclusion Criteria ........................................................................................................... 7 
5.4 
Randomization ............................................................................................................... 8 
6.0 
PROCEDURES ............................................... 8 
6.1 
Surgical Procedure ......................................................................................................... 8 
6.2 
Medical Record Requirements ....................................................................................... 8 
6.3 
Data Collection ............................................................................................................... 8 
6.4 
Schedule of Assessments .............................................................................................. 9 
7.0 
STATISTICAL ANALYSIS ............................ 10 
8.0 
ADVERSE EVENT ASSESSMENT .............. 10 
8.1 
Adverse Event (AE) ...................................................................................................... 10 
8.2 
Serious Adverse Events (SAE) .................................................................................... 10 
8.3 
Adverse Event Relationship ......................................................................................... 10 
9.0 
INVESTIGATOR RESPONSIBILITIES, RECORD 
AND REPORTS ....................................................... 11 
9.1 
Subject Consent and Information ................................................................................. 11 
9.2 
Subject Data Protection ............................................................................................... 11 
9.3 
Staff Information ........................................................................................................... 11 
9.4 
Protocol Reviews.......................................................................................................... 11 

 
Protocol Number: 2023-0063  
Version Date: 5/23/2023  
 
Confidential 
Page 3 of 12 
 
10.0 
REFERENCES ........................................... 11 
 
 
 

 
Protocol Number: 2023-0063  
Version Date: 5/23/2023  
 
Confidential 
Page 4 of 12 
 
PROTOCOL SYNOPSIS 
Protocol Title: 
A Randomized Controlled Trial of Ultrasound Guided Knee 
Genicular Nerve Block and Anterior Femoral Cutaneous 
Nerve Block for Primary Total Knee Arthroplasty 
Protocol Number: 
2023-0063 
Protocol Date: 
5/23/2023 
Sponsor: 
Anesthesiology Department 
Principal 
Investigator: 
Jiabin Liu, MD/PhD 
Products: 
N/A 
Objective: 
The purpose of this study is to conduct a randomized 
controlled trial on patients undergoing unilateral total knee 
arthroplasty to assess the benefits of adding genicular and 
anterior femoral cutaneous nerve block. 
Study Design: 
Randomized Clinical Trial 
Enrollment: 
244 
Subject Criteria: 
Inclusion: 
• patients age 18-80 
• patients undergoing ambulatory unilateral total knee 
arthroplasty, including 23 hours stay cohort 
• ASA I-III 
• BMI < 35 
Exclusion: 
• history of chronic pain syndromes 
• chronic opioid use (daily morphine milligram 
equivalents > 30 mg for at least 3 months) 
• contraindication to peripheral nerve blocks 
• contraindication to neuraxial anesthesia 
• history of peripheral neuropathy or pre-existing 
neurological deficits 
• Psychiatric or cognitive disorder that prohibit patient 
from following study protocol 
• allergy to local anesthetic or study medications 
• multiligament surgery 
• history of substance abuse 
• infection at the site of injection 
• chronic kidney disease 
Study Duration: 
• 2 years 

 
Protocol Number: 2023-0063  
Version Date: 5/23/2023  
 
Confidential 
Page 5 of 12 
 
Data Collection: 
Sources: EPIC, Medical Records, and Patient Reported. 
 
Variables: Name, MRN, DOB, Race, Ethnicity, Gender, 
Height, Weight, BMI, phone number, comorbidities, 
medications to manage existing conditions, surgery details, 
anesthesia details, opioid consumption, NRS pain scores, 
length of PACU stay, time to meet discharge, nerve block 
success, brief pain inventory, patient satisfaction, 
analgesic duration of the blocks, time of discontinuing 
opioids, bang blinding index 
Statistical Analysis: Proposed analysis: 
Two sample t-test (two-sided) 
Chi-square test (two-sided) proportion 
Interim analysis planned? No 
Alpha level: .025 
Beta or power level: .80 
Number of groups being compared: 2 
Resulting number per group: 122 
Total sample size: 244 
 
 
 
 

 
Protocol Number: 2023-0063  
Version Date: 5/23/2023  
 
Confidential 
Page 6 of 12 
 
1.0 INTRODUCTION 
Adductor canal nerve block (ACB), infiltration between the popliteal artery and the 
posterior knee capsule (IPACK), with or without peri-articular infiltration of local 
anesthetics (PAI), is the current standard of practice for analgesia coverage after 
total knee arthroplasty at the Hospital for Special Surgery. However, we frequently 
see patients with moderate post-operative knee pain, particularly on the anterior, 
middle, and lateral sides of the knee. There is limited clinical research on if adding a 
genicular nerve block could offer TKA patients a more complete analgesia. 
2.0 OBJECTIVE OF CLINICAL STUDY 
This study will test if the addition of genicular nerve block (including superolateral 
genicular nerve, superomedial genicular nerve, inferomedial genicular nerve, and 
nerve to vastus intermedius) and anterior femoral cutaneous nerve block could offer 
TKA patients a more complete analgesia. The primary outcomes of interest are the 
numerical rating scale (NRS) pain score, measured as the worst pain experienced, 
in the PACU and total opioid consumption within the first 24 hours of surgery. 
Secondary outcomes of interest include post-operative opioid use (up to 7 days) and 
readiness for home discharge. 
3.0 STUDY HYPOTHESES 
Hypothesis 1: There is no relationship between adding genicular nerve block and 
anterior femoral cutaneous nerve block to provide more complete analgesia and the 
use less oral and intravenous medication after TKA. 
Hypothesis 2: There is no relationship between the addition of genicular nerve block 
and anterior femoral cutaneous nerve block and reduced opioid consumption. 
4.0 STUDY DESIGN 
 
4.1 Study Duration 
2 years 
4.2 Endpoints 
4.2.1 Primary Endpoint 
• The average pain score in the post-anesthesia care unit 
• The cumulative opioid consumption within the first 24 hours after 
surgery 

 
Protocol Number: 2023-0063  
Version Date: 5/23/2023  
 
Confidential 
Page 7 of 12 
 
4.2.2 Secondary Endpoints 
• The average pain score at 24 & 48 hours after surgery 
• Cumulative opioid consumption at 24, 48, and 168 hours after surgery 
• The severity of pain and impact on functioning in the PACU and 168 
hours after surgery 
• Patient satisfaction with pain management in the PACU and 168 hours 
after surgery 
• Time of discharge 
• Bang blinding index 
 
4.3 Study Sites 
Hospital for Special Surgery – Main Campus 
5.0 STUDY POPULATION 
5.1 Number of Subjects 
A total of 244 subjects will be enrolled. 
 
5.2 Inclusion Criteria 
Subjects of either gender will be included if they: 
• patients age 18-80 
• patients undergoing ambulatory unilateral total knee arthroplasty, including 23 
hour stay cohort 
• ASA I-III 
• BMI < 35 
5.3 Exclusion Criteria 
Subjects will be excluded from the study if they: 
• history of chronic pain syndromes 
• chronic opioid use (daily morphine milligram equivalents > 30 mg for at least 3 
months) 
• contraindication to peripheral nerve blocks 
• contraindication to neuraxial anesthesia 
• history of peripheral neuropathy or pre-existing neurological deficits 
• Psychiatric or cognitive disorder that prohibits patient from following study 
protocol. 
• allergy to local anesthetic or study medications 
• multiligament surgery 
• history of substance abuse 
• infection at the site of injection 

 
Protocol Number: 2023-0063  
Version Date: 5/23/2023  
 
Confidential 
Page 8 of 12 
 
• chronic kidney disease 
5.4 Randomization 
A computer-generated, 1:1 ratio randomization schedule with blocks of sizes 
4 and 6 will be created by a statistician not otherwise involved in the study. 
Participants will be randomized to 1 of 2 groups: 
• Group 1 Standard Total Knee Arthroplasty 
• Group 2 Genicular Total Knee Arthroplasty 
6.0 PROCEDURES 
6.1 Surgical Procedure 
Total Knee Arthroplasty/Replacement 
6.2  Medical Record Requirements 
EPIC 
6.3 Data Collection 
The following data will be collected: 
 
Pre-operative/Baseline 
• basic demographic data 
• patient weight & height, BMI 
 
Surgical procedure 
• date of surgery 
• type of surgery 
• surgery details 
• anesthesia details 
 
Follow-up visits (PACU, POD1, POD2, POD7) 
• Medication intake 
• Numerical Rating Scale (NRS) Pain Score 
• Brief Pain Inventory 
• Analgesic duration 
• Patient satisfaction 
• Opioid discontinuation 

Confidential 
Page 9 of 12 
 
 
6.4 Schedule of Assessments 
Procedures 
Pre-Op 
Day of 
Sugery 
PACU 
POD 1 
POD 2 
POD 7 
Identify eligible patients on 
schedule 
X 
 
 
 
 
 
Introduce study to patient 
X 
X 
 
 
 
 
Randomization 
 
X 
 
 
 
 
Obtain consent 
 
X 
 
 
 
 
Administer Intervention 
 
X 
 
 
 
 
NRS Pain Score 
 
X 
X 
X 
X 
X 
Brief Pain Inventory 
 
X 
 
 
 
X 
Analgesic Duration 
 
 
 
X 
X 
X 
Patient Satisfaction 
 
 
X 
 
 
X 
Opioid Discontinuation 
 
 
 
 
 
X 
Bang Blinding Index 
 
 
 
 
 
X 

Confidential 
Page 10 of 12 
 
 
 
7.0 STATISTICAL ANALYSIS 
Proposed analysis: 
Two sample t-test (two-sided) 
Chi-square test (two-sided) proportion 
Interim analysis planned? No 
Alpha level: .025 
Beta or power level: .80 
Number of groups being compared: 2 
Resulting number per group: 122 
Total sample size: 244 
 
8.0 ADVERSE EVENT ASSESSMENT 
All Adverse Events (AEs) will be reported in the final study report. Definitions for 
Adverse Event (AE) used in this study are listed below and are based on FDA and 
international guidelines: 
 
8.1 Adverse Event (AE) 
Any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product which does not necessarily have to 
have a causal relationship with this treatment. An adverse event (AE) can 
therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding, for example), symptom, or disease temporally associated 
with the use of a medicinal (investigational) product, whether or not 
considered related to the medicinal (investigational) product. 
 
8.2 Serious Adverse Events (SAE) 
The event is serious and should be reported to FDA when the patient 
outcome is: 
Death, Life-threatening, Hospitalization (initial or prolonged), Disability or 
Permanent Damage, Congenital Anomaly/Birth Defect, Required Intervention 
to Prevent Permanent Impairment or Damage (Devices), Other Serious 
(Important Medical Events). 
 
8.3 Adverse Event Relationship 
Relationship to study: definitely, probably, possibly, not related. 
 

 
Protocol Number: 2023-0063  
Version Date: 5/23/2023  
 
Confidential 
Page 11 of 12 
 
9.0 INVESTIGATOR RESPONSIBILITIES, RECORD AND REPORTS 
 
9.1 Subject Consent and Information 
Research assistants will screen the co-investigating surgeons' patients 
undergoing ambulatory total knee arthroplasty surgery. Screening will involve 
reviewing the patient's EPIC chart to ensure that they meet the inclusion criteria 
and are not excluded due to any of the exclusion criteria listed. Patients who 
meet the inclusion criteria will be identified as potential study participants. After 
the investigating anesthesiologists have confirmed the eligibility of all potential 
participants, one of the investigating anesthesiologists will approach the 
potential patients in the pre-operative holding area, explain the rationale for the 
study, and ask if the patient is interested in participating. 
9.2 Subject Data Protection 
Subject privacy and confidentiality will be maintained through the storage of 
study data in a password-protected computer database maintained by the 
Research Director and accessible only to the principal investigator, in addition 
to other IRB-approved study personnel. Each subject will be assigned a unique 
study number for identification in the study database. This unique study 
number will not be derived from or related to information about the individual. 
The key linking this unique study number to patient identifiers (i.e., name, 
medical record number, date of birth, registry number) will be maintained in a 
different password-protected database maintained by Research Director, to 
which only the primary investigator will have access. 
9.3 Staff Information 
Primary Investigator: Jiabin Liu, MD/PhD 
Research Coordinator: Pa Thor, PhD, 646-797-8535 
Research Assistant: Miriam Sheetz 
 
9.4 Protocol Reviews 
Study protocol reviewed and approved by: 
• Anesthesiology CRP 
• Hospital for Special Surgery Institutional Review Board 
10.0 REFERENCES 
1. Conger A, Gililland J, Anderson L, Pelt CE, Peters C, McCormick ZL. 
Genicular Nerve Radiofrequency Ablation for the Treatment of Painful 
Knee Osteoarthritis: Current Evidence and Future Directions. Pain Med. 
2021 Jul 25;22(Suppl 1):S20-S23. doi: 10.1093/pm/pnab129.   PubMed 
ID: 34308957 

 
Protocol Number: 2023-0063  
Version Date: 5/23/2023  
 
Confidential 
Page 12 of 12 
 
2. Kim DH, Choi SS, Yoon SH, Lee SH, Seo DK, Lee IG, Choi WJ, Shin JW. 
Ultrasound-Guided Genicular Nerve Block for Knee Osteoarthritis: A 
Double-Blind, Randomized Controlled Trial of Local Anesthetic Alone or in 
Combination with Corticosteroid. Pain Physician. 2018 Jan;21(1):41-
52.   PubMed ID: 29357330 
3. Rambhia M, Chen A, Kumar AH, Bullock WM, Bolognesi M, Gadsden J. 
Ultrasound-guided genicular nerve blocks following total knee arthroplasty: 
a randomized, double-blind, placebo-controlled trial. Reg Anesth Pain 
Med. 2021 Oct;46(10):862-866. doi: 10.1136/rapm-2021-102667. Epub 
2021 Jul 14.   PubMed ID: 34261807