Clinical trial NCT05286307
Conditions: Anterior Cruciate Ligament Rupture
Sponsor: NYU Langone Health
Start date: 2022-07-11; Completion date: 2023-12-18
Enrollment: 102 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A randomized, single-blind, single-center study measuring the effects of adductor canal block combined with IPACK infiltration compared to adductor canal block alone on post-operative pain and opioid consumption in patients undergoing ACL reconstruction with Bone Patellar Tendon Bone Autograft

Detailed description:
The protocol will determine if the addition of an IPACK block to the standard adductor canal block is superior to an isolated adductor canal block in controlling post-operative pain and decreasing postoperative opioid consumption in patients undergoing ACLR with Bone Patellar Tendon Bone Autograft

Arms: arm 1: Patients in this study group will receive the standard of care adductor canal block composed of 15 mL of Bupivacaine (0.25%). And receive the additional IPACK block performed using 20 mL of Bupivacaine (0.25%) injected into the interspace between the popliteal artery and capsule of the knee. arm 2: Patients in the control group will receive the standard of care adductor canal block composed of 15 mL of Bupivacaine (0.25%).
Interventions: intervention 1: IPACK block
Intervention descriptions: intervention 1: IPACK block with 20 mL of 0.25% Bupivacaine injected into the Interspace between the Popliteal Artery and Capsule of the Knee

Protocol documents:
Prot_SAP_000.pdf: 
 
 
Official Title: 
Adductor Canal Block and IPACK Block vs. Isolated Adductor Canal 
Block for Post-Operative Analgesia Following ACL Reconstruction With 
Bone Patellar Tendon Bone Autograft: A Single Center Randomized 
Placebo-Controlled Trial   
NCT Number: 
NCT05286307 
Study Number: 
22-00148 
Document Type:  
Study Protocol and Statistical Analysis Plan 
Date of the 
Document: 
• 
March 14, 2022 
 
 


Study#: s22-00148 
Version date: 02.24.2022 
  
CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as 
authorized in writing by the study sponsor 
 
 
 
 
 
ADDUCTOR CANAL BLOCK PLUS IPACK BLOCK VS ISOLATED 
ADDUCTOR CANAL BLOCK FOR POSTOPERATIVE ANALGESIA IN 
ACLR WITH BONE PATELLAR TENDON BONE AUTOGRAFT 
 
 
 
Principal Investigator: 
 
 
Eric J. Strauss MD 
Department of Orthopedic Surgery 
NYU Langone Health  
NYU Langone Orthopedic Hospital  
301 East 17th Street  
New York, NY 10003 
Eric.Strauss@nyulangone.org 
 
Co-PIs 
David Furgiuele MD 
Department of Anesthesiology 
NYU Langone Health 
NYU Langone Orthopedic Hospital  
301 East 17th Street  
New York, NY 10003 
David.Furgiuele@nyulangone.org 
 
 
Jovan Popovic MD 
Department of Anesthesiology 
NYU Langone Health 
NYU Langone Orthopedic Hospital  
301 East 17th Street  
New York, NY 10003 
Jovan.Popovic@nyulangone.org 
 
 
 
 
 
 
NYULMC Study Number: 
i22-00148 
Study Product: 
N/A 
 
 


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Statement of Compliance 
 
This study will be conducted in accordance with the Code of Federal Regulations on the Protection of 
Human Subjects (45 CFR Part 46), 21 CFR Parts 50, 56, 312, and 812 as applicable, any other applicable 
US government research regulations, and institutional research policies and procedures. The 
International Conference on Harmonisation (“ICH”) Guideline for Good Clinical Practice (“GCP”) 
(sometimes referred to as “ICH-GCP” or “E6”) will be applied only to the extent that it is compatible with 
FDA and DHHS regulations. The Principal Investigator will assure that no deviation from, or changes to 
the protocol will take place without prior agreement from the sponsor and documented approval from 
the Institutional Review Board (IRB), except where necessary to eliminate an immediate hazard(s) to the 
trial participants. All personnel involved in the conduct of this study have completed Human Subjects 
Protection Training. 
 
 


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Table of Contents 
STATEMENT OF COMPLIANCE ................................................................................................................................... II 
PROTOCOL SUMMARY ................................................................................................................................................... 6 
1 
BACKGROUND AND SPECIFIC AIMS............................................................................................................ 8 
1.1 
SPECIFIC AIMS ..................................................................................................................................................................... 8 
1.2 
STATISTICAL HYPOTHESIS ................................................................................................................................................ 8 
1.3 
OBJECTIVES AND PURPOSE ............................................................................................................................................... 9 
2 
STUDY DESIGN AND ENDPOINTS ................................................................................................................ 9 
2.1 
DESCRIPTION OF STUDY DESIGN ..................................................................................................................................... 9 
2.2 
SCHEMATIC OF STUDY DESIGN ...................................................................................................................................... 11 
3 
STUDY ENROLLMENT AND WITHDRAWAL .......................................................................................... 12 
3.1 
INCLUSION CRITERIA ...................................................................................................................................................... 12 
3.2 
EXCLUSION CRITERIA ..................................................................................................................................................... 12 
3.3 
VULNERABLE SUBJECTS.................................................................................................................................................. 12 
3.4 
RECRUITMENT AND CONSENT ....................................................................................................................................... 12 
3.5 
DURATION OF STUDY PARTICIPATION ......................................................................................................................... 13 
3.6 
TOTAL NUMBER OF PARTICIPANTS AND SITES .......................................................................................................... 13 
3.7 
PARTICIPANT WITHDRAWAL OR TERMINATION ....................................................................................................... 14 
3.8 
PREMATURE TERMINATION OR SUSPENSION OF STUDY .......................................................................................... 14 
4 
STUDY PROCEDURES AND SCHEDULE ................................................................................................... 14 
4.1 
STUDY PROCEDURES/EVALUATIONS ........................................................................................................................... 14 
 
 
4.1.1 
STUDY SPECIFIC PROCEDURES ................................................................................................................................ 14 
 
 
4.1.2 
STANDARD OF CARE STUDY PROCEDURES ............................................................................................................ 14 
4.2 
STUDY SCHEDULE ............................................................................................................................................................ 15 
 
 
4.2.1 
SCREENING .................................................................................................................................................................. 15 
 
 
4.2.2 
ENROLLMENT/BASELINE ......................................................................................................................................... 15 
 
 
4.2.3 
FOLLOW-UP  (POD 1 POD 2 AND POD 3) .......................................................................................................... 15 
            4.2.3.    Follow-Up Postop Visit 1…………………………………………………………………………….………………..15 
 
 
4.2.4 
WITHDRAWAL/EARLY TERMINATION VISIT ........................................................................................................ 15 
4.3 
CONCOMITANT MEDICATIONS, TREATMENTS, AND PROCEDURES ......................................................................... 15 
5 
RISKS AND BENEFITS ................................................................................................................................... 15 
5.1 
POTENTIAL RISKS ............................................................................................................................................................ 15 
5.2 
POTENTIAL BENEFITS ..................................................................................................................................................... 16 
6 
STATISTICAL ANALYSIS .............................................................................................................................. 16 
6.1 
GENERAL APPROACH ...................................................................................................................................................... 16 
6.2 
ANALYSIS OF ENDPOINTS ............................................................................................................................................... 16 
6.3 
SAMPLE SIZE .................................................................................................................................................................... 17 
6.4 
ENROLLMENT/RANDOMIZATION/MASKING PROCEDURES ..................................................................................... 17 
6.5 
BREAKING THE STUDY BLIND/PARTICIPANT CODE ................................................................................................. 17 
7 
ASSESSMENT OF SAFETY ............................................................................................................................ 17 
7.1 
DEFINITION OF ADVERSE EVENTS (AE) ..................................................................................................................... 18 
7.2 
DEFINITION OF UNANTICIPATED PROBLEMS (UP) ................................................................................................... 18 
7.3 
CLASSIFICATION OF AN ADVERSE EVENT .................................................................................................................... 18 
 
 
7.3.1 
SEVERITY OF EVENT .................................................................................................................................................. 18 


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7.3.2 
RELATIONSHIP TO STUDY AGENT ........................................................................................................................... 19 
 
 
7.3.3 
EXPECTEDNESS ........................................................................................................................................................... 20 
7.4 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP ...................................................... 20 
7.5 
REPORTING PROCEDURES – NOTIFYING THE IRB ..................................................................................................... 20 
 
 
7.5.1 
UNANTICIPATED PROBLEM REPORTING ................................................................................................................ 20 
7.6 
STUDY HALTING RULES ...................................................................................... ERROR! BOOKMARK NOT DEFINED. 
7.7 
SAFETY OVERSIGHT ........................................................................................................................................................ 21 
8 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ........................................ 21 
9 
QUALITY ASSURANCE AND QUALITY CONTROL ................................................................................. 22 
10 
ETHICS/PROTECTION OF HUMAN SUBJECTS ...................................................................................... 22 
10.1 
ETHICAL STANDARD ....................................................................................................................................................... 22 
10.2 
INSTITUTIONAL REVIEW BOARD1 ................................................................................................................................ 22 
10.3 
PARTICIPANT AND DATA CONFIDENTIALITY .............................................................................................................. 23 
11 
DATA HANDLING AND RECORD KEEPING ............................................................................................ 23 
11.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES .................................................................................... 23 
11.2 
STUDY RECORDS RETENTION ........................................................................................................................................ 24 
11.3 
PROTOCOL DEVIATIONS ................................................................................................................................................. 24 
11.4 
PUBLICATION AND DATA SHARING POLICY ................................................................................................................ 24 
12 
STUDY FINANCES ........................................................................................................................................... 25 
12.1 
FUNDING SOURCE ............................................................................................................................................................ 25 
12.2 
COSTS TO THE PARTICIPANT ......................................................................................................................................... 25 
12.3 
PARTICIPANT REIMBURSEMENTS OR PAYMENTS ...................................................................................................... 25 
13 
CONFLICT OF INTEREST POLICY .............................................................................................................. 25 
14 
REFERENCES ................................................................................................................................................... 26 
15 
ATTACHMENTS .............................................................................................................................................. 27 
15.1 
OPIOID EQUIVALENTS ..................................................................................................................................................... 27 
15.2 
BASELINE ASSESSMENTS .................................................................................... ERROR! BOOKMARK NOT DEFINED. 
15.3 
MEDICATION USAGE RECORD  .......................................................................... ERROR! BOOKMARK NOT DEFINED. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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List of Abbreviations 
 
ACLR 
Anterior Cruciate Ligament Reconstruction 
 
BPTB 
Bone Patellar Tendon Bone 
 
IPACK 
Interspace between the Popliteal Artery and Capsule of the Knee 
 
ACB 
Adductor Canal Block 
 
ASA 
American Society of Anesthesiologist Score 
 
BMI 
Body Mass Index 
 
DOS 
Day of surgery 
 
VAS 
Visual analog scale 
 
AE 
Adverse event 
 
SAE 
Serious adverse event 
 
IV 
Intravenous 
 
ITT 
Intention-to-treat 
 
PACU 
Post-Anesthesia Care Unit 
 
PO 
Taken orally 
 
CI 
Confidence interval 
 
SD 
Standard deviation; a parameter that characterizes a population distribution 
 
SE 
Standard error 
 
ANOVA 
Analysis of variance; a linear model   
 
NSAID 
Non-steroidal anti-inflammatory drug 


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Protocol Summary 
Title 
Adductor Canal Block and IPACK Block vs. Isolated Adductor Canal Block for 
Post-Operative Analgesia Following ACL Reconstruction with Bone Patellar 
Tendon Bone Autograft: A Single Center Randomized Placebo-Controlled 
Trial.  
Brief Summary 
A randomized, single-blind, single-center study measuring the effects of 
adductor canal block combined with IPACK infiltration compared to adductor 
canal block alone on post-operative pain and opioid consumption in patients 
undergoing ACL reconstruction with Bone Patellar Tendon Bone Autograft 
 
Objectives 
To determine if the addition of an IPACK block to the standard adductor canal 
block is superior to an isolated adductor canal block in controlling post-
operative pain and decreasing postoperative opioid consumption in patients 
undergoing ACLR with Bone Patellar Tendon Bone Autograft 
Methodology 
Randomized, single-blind, single-center study 
Endpoint 
Primary Endpoint:  
Opioid utilization for the first 72 hours after surgery, including during surgery, 
calculated as morphine equivalent. 
 
Secondary Endpoints:   
Opioid consumption Post-operatively 
Patient reported VAS scores in PACU 
Length of stay in PACU 
Patient reported VAS scores on POD 1, POD 2, POD 3, POD 7 
Reaction to IPACK block 
Incidence of postoperative complications 
Study Duration 
The study will continue until 50 subjects are enrolled per arm, to allow for 
potential dropout and increased power. 
Participant Duration 
Each participant will be enrolled on DOS and complete their final follow up on 
postoperative day seven. 
Duration of IP 
administration 
Once during surgery 
Population 
50 patients per study arm scheduled for ACLR with BPTB autograft 
Study Sites 
NYU Langone Orthopedic Hospital and NYU Ambulatory Surgery Center at 
38th street 
Number of 
participants 
100 
Description of Study 
Agent/Procedure 
Patients in both the study and control group will receive the standard of care 
adductor canal block composed of 15 mL of Bupivacaine (0.25%). Patients in 
the study group will receive the additional IPACK block performed using 20 
mL of Bupivacaine (0.25%) injected into the interspace between the popliteal 
artery and capsule of the knee. Patients will be blinded to their group 
allocation.   
Reference Therapy 
Reference is isolated adductor canal block 
Key Procedures 
Adductor canal block 15 mL 0.25% Bupivacaine, IPACK block with 20 mL 
0.25% bupivacaine  


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Statistical Analysis 
Continuous and categorical baseline characteristics will be compared using 
Hedges standardized difference. Normally distributed data will be compared 
using t tests while non-normally distributed continuous outcomes will be 
assessed using the Mann-Whitney U test. 
 
  
 
 
 


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1 Background and Specific Aims 
Anterior cruciate ligament (ACL) reconstructions are among the most commonly performed outpatient 
orthopedic procedures, with approximately 400,000 ACLRs performed each year.1 Outcomes following ACL 
reconstruction (ACLR) are excellent, with low rates of graft failure and high rates of return to pre-injury 
function.2,3 Despite these positive outcomes, post-operative pain and discomfort is a commonly cited 
complaint following ACLR. Pain control following ACLR is multimodal, including peripheral nerve blocks 
intraarticular injections, oral, and IV medications.4  However, given the rise in reported rates of addiction to 
opioids and high prescribing patterns among orthopedic surgeons, alternative pain control modalities must 
be explored.4,5  
 
For arthroscopic ACLR with Bone Patellar Tendon Bone (BPTB) autograft, assuming there are no contra-
indications, anesthesiologists at our institution perform a block of the saphenous nerve via the adductor 
canal, also known as adductor canal block (ACB).  When compared to a femoral nerve block (FNB), the 
adductor canal block has been shown to have equivalent analgesia without the undesired quadriceps 
weakness associated with FNBs.6-8 While these peripheral blocks have proven to be effective, they spare 
sensory function to the posterior knee compartment, leading to posterior knee pain postoperatively. This 
portion of the knee, innervated by the common peroneal nerve, obturator nerve, and tibial nerves, can be a 
source of pain for patients following knee surgery.9 The IPACK block seeks to reduce pain in the posterior 
aspect of the knee, while sparing quadriceps strength. There have been several studies looking at the use of 
IPACK block in arthroplasty; these studies have found a short term improved analgesic effect of decreased 
pain scores while in the post anesthesia care unit (PACU), however they did not find significant differences 
in amount of narcotics used postoperativly.6,9-11 In a study looking at ACLR with femoral block + IPACK and 
local infiltration anesthesia, patients who underwent IPACK and femoral block had lower postoperative IV 
morphine consumption within 24 hours of surgery.12 To date, there have been no studies looking at 
analgesia using IPACK block combined with adductor canal block for patient undergoing ACLR in the 
ambulatory setting.  With this blinded randomized control trial, we seek to elucidate the added benefit of an 
IPACK  block and to determine if it leads to improved pain control and decreased opioid use following ACLR 
with BPTB autograft.  
1.1 Specific Aims 
This study will aim to compare ACB + IPACK block versus ACB only for posterior knee pain in patients 
undergoing ACLR with BPTB autograft.   
 
AIM 1:  To determine if the addition of IPACK block to the standard of care ACB is superior in terms of 
decreasing opioid consumption, decreasing pain, and increasing analgesia duration following anterior 
cruciate ligament reconstruction.  
 
1.2 Statistical Hypothesis 
We hypothesize that patients who receive an IPACK block plus an ACB will have lower postoperative opioid 
consumption over the first 24 hours (measured in morphine equivalents) compared to those who an isolated 
ACB following anterior cruciate ligament reconstruction. Furthermore, the study group will report lower 
postoperative pain scores on POD1 than the control group. Failing to reject the null would signify that the 
IPACK block has no clinically relevant difference on post-operative opioid consumption outcomes following 
ACLR with BPTB autograft.  
 


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1.3 Objectives and Purpose 
The goal of this study is to determine if the addition of IPACK block to the standard of care adductor canal 
block is superior to an isolated adductor canal block in decreasing postoperative pain, decreasing opioid 
consumption, and leads to increased duration of analgesia in patients undergoing ACLR. The primary 
objective will be to compare opioid utilization between the two arms within the first 72 hours after surgery, 
including intraoperatively, as measured by morphine equivalents. Our secondary objectives are measuring 
patient reported pain scores in PACU at 24 hours, 48 hours, and 72 hours, and at the first postoperative visit 
(POD 7).  
 
2 Study Design and Endpoints 
 
 
Arm 1: Experimental 
 
 
Arm 2: Control 
 
Sample Size: 50 
 
 
Sample Size: 50 
 
Medication: 15 mL of 0.25% Bupivacaine block 
of the saphenous nerve injected under 
ultrasound guidance via adductor canal and 
IPACK block with 20 mL of 0.25% Bupivacaine 
injected into the Interspace between the Popliteal 
Artery and Capsule of the Knee 
 
 
 
Medication: 15 mL of 0.25% Bupivacaine block 
of the saphenous nerve injected under 
ultrasound guidance via adductor canal 
 
2.1 Description of Study Design 
RECRUITMENT PHASE/CONSENTING PHASE: 
Surgeons will identify eligible patients via Epic during their initial clinic visit and discuss the study. Surgeons 
will provide research coordinator with the name and medical record number of eligible patients.  If the patient 
meets the inclusion criteria outlined below and is agreeable, subjects will be first introduced to the study 
during one of their presurgical clinic visits and then consented on the day of surgery by a member of the 
research team.  Patients will be made acquainted with the study prior to surgery. On DOS when they arrive 
1.5/2 hours before surgery, we (study team members) will consent them in a private room and provide ample 
time to discuss and review any questions or concerns they may have.  
 
BASELINE ASSESSMENTS:  
Subjects will complete a baseline VAS McGill Pain scale, Kujala, KOOS-PS and Tegner Activity Scale 
 
RANDOMIZATION PHASE:  
Subjects scheduled to undergo ACLR with BPTB autograft will be randomized to either ACB with IPACK block 
or to ACB only. A randomization scheme will be created prior to start of study enrollment using the 
randomizer.org website to generate the assignment. Block randomization is commonly used in clinical trial 
design to reduce bias  and achieve balance in the allocation of participants to treatment arms throughout the 
course of the study. Randomized block design allows us to account for variables so that observed differences 
are largely due to true differences between  treatments and not to the variable. We will create blocks of four 
patients and in each block, two patients will be assigned to the IPACK + ACB group, and two to the ACB only 


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group. Thus, patients in both groups with be evenly spread from the beginning to the end of the study. 
  
A research coordinator will place the randomization results in sealed envelopes prior to recruitment.  Each 
subject enrolled in the study will be assigned a number and the sealed envelope assigning the subject to the 
IPACK + ACB or ACB only will be opened on the day of surgery after the patient has signed consent agreeing 
to participate in the study. 
 
Patients will be blinded to their group allocation. During peripheral block patients are sedated and 
postoperatively, the areas of infiltration will be covered by bandage.  
 
TREATMENT PHASE:  
 
Patients in both the study and control group will receive the standard of care adductor canal block. This 
consists of 15mL of bupivacaine (0.25%) Injected under ultrasound guidance in the saphenous nerve via the 
adductor canal. Patients in the study group will receive the additional IPACK block performed using 20 mL 
of bupivacaine (0.25%) injected into the interspace between the popliteal artery and capsule of the knee.  
 
 
POST-OPERATIVE PHASE:  
After initial recruitment, subjects’ pain will be assessed via visual analog scale (VAS) by nursing staff during 
the post-operative period as per standard of care in the post anesthesia care unit, and by the research staff 
prior to leaving the surgical center. The VAS pain scores are collected and documented in the patient’s 
electronic medical record. Additionally, a standardized regimen of pain medication will be given to all subjects 
who are enrolled. The pain medications given to patients are standard of care medication 325-5 mg Percocet 
and vary based on pain level. This is determined by the clinical staff caring for each patient.  While the patient 
is in the PACU prior to discharge, an authorized research member will visit the patient and obtain a pain score 
using the VAS and McGill Pain Scale. Data on PACU opioid use documented in the electronic medical record 
will be collected. On POD1, POD 2 and POD 3, a phone call or email survey will be sent to the patient to collect 
additional data on opioid use at home as well as a VAS score at 24, 48, and 72 hours after surgery.  
 
 


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2.2 Schematic of Study Design 
  
 
 
 
 
Patient will be seen in standard fashion by surgeon on POD7 for their first 
follow up visit. Where the block area will be examined, and final pain scales 
(McGill and VAS) will be administered.  
100 subjects: Obtain informed consent. Screen potential subjects by inclusion and 
exclusion criteria; obtain history. Scales: VAS, McGill, KOOS-PS, KUJALA, Tegner 
Activity Scale 
Randomize 
50 Subjects: ACB + IPACK 
Block  
50 subjects: ACB only 
Assess reaction to skin incision, opioid requirements 
Assess pain score, skin sensation test, continue opioid requirement 
assessment, administer pain questionnaire 
Patients will receive a text message 24 hours, 48 hours, and 72 hours 
following PACU Discharge, to collect additional data on opioid use, pain 
level, and any residual loss of sensation, paresthesia, foot drop, or skin 
reaction in the block distribution 
Final Assessments: Opioid 
requirements, pain scores, pain 
questionnaire, strength (foot drop) 
Intraoperative 
Measurements 
Enrollment 
PACU 
Measurements 
After discharge 
measurements 
Data compilation 
Post Op Visit 1 
(Day 7) 
Patient will be seen in standard fashion at their 6 month postoperative visit 
scales will be administered: VAS, KOOS-PS, KUJALA, Tegner Activity Scale  
Early Functional 
Outcomes 


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3 Study Enrollment and Withdrawal 
The researchers will approach patients scheduled for primary ACLR and are eligible for participation in the 
study. Anesthesiology/Sports Medicine attendings, fellows, residents, and authorized researchers will 
consent and enroll patients pre-operatively.  
3.1 Inclusion Criteria 
• 
Patients between 18 and 75 years of age 
• 
Patients undergoing primary ACL reconstruction with BPTB Autograft 
• 
ASA I or II 
3.2 Exclusion Criteria 
• 
Patients younger than 18 and older than 75. 
• 
Patients with multi-ligament injury 
• 
Patients undergoing concomitant cartilage procedure or osteotomy.  
• 
Patients with a history of chronic pain that have used opioids for pain management for 3 months or 
longer. 
• 
Patients who are allergic to oxycodone; 
• 
Patients with diagnosed or self-reported cognitive dysfunction; 
• 
Patients with a history of neurologic disorder that can interfere with pain sensation; 
• 
Patients with a history of drug or recorded alcohol abuse; 
• 
Patients who are unable to understand or follow instructions; 
• 
Patients with severe liver disease, renal insufficiency, congestive heart failure, and/or significant heart 
disease; 
• 
Patients with an allergy or contraindication to any of the medications used in the study, or patients with 
a contraindication to any study procedures; 
• 
Patients with a BMI over 45;  
• 
Any patient that the investigators feel cannot comply with all study related procedures; 
• 
Any pregnant patient; assessed via urine pregnancy test in the preoperative area as part of standard 
preoperative surgical protocol; 
3.3 Vulnerable Subjects 
No vulnerable populations will be enrolled in this study.  
3.4 Recruitment and Consent 
Surgeon will identify potential subjects during their initial preoperative visit at which the surgeon will discuss 
the study with the patient. Should the potential subjects agree, the surgeon will provide the researcher with 
the name and medical record number of the patient. Researchers will receive the name and MRN of potential 
subjects identified by treating physician (study team members not volunteers) will utilize EPIC to extract 
patient demographic and surgical information to determine study eligibility. Once eligibility is confirmed, the 
treating physicians (TPs) will be notified via email, and they will discuss the study with the patient in the clinic 
at least 1 day prior to surgery to allow potential subjects to review and consider participation in the study. 
 
If a subject requests information regarding opting out of further recruitment for all research, subjects will be 
directed to contact study coordinator or have subjects contact research-contact-optout@nyumc.org or 1-855-
777-7858. 
 
 


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Written consent will then be obtained on the day of surgery in the preoperative holding area by an authorized 
research team member or the treating physician (surgeon or anesthesiologist). Once the patient is enrolled, 
they will be assigned a subject ID number and be randomized into a treatment group. 
 
Once enrolled in the study, subject medical records will be accessed once more after surgery (for the second 
and final time) using subject MRNs by authorized study team members to collect demographic data including 
age, BMI, sex, smoking history, past surgical history, intraoperative findings, and opioid consumption (mgs) 
in the PACU. Once collected, deidentified data will be stored in the MCIT-managed HIPAA-compliant and 
encrypted version of Redcap in addition to the MCIT governed, firewall protected shared drive located on the 
NYU MCIT network.  
 
Data linking protected health information to the deidentified patient record number will be kept in a local 
password-protected computer. Only the principal investigator will have access to the identified data.  
 
Process of Consent 
Written consent for participation will be obtained on day of surgery in pre-operative holding room by the 
Attending Physicians, or authorized researchers that are members of the study team. Extensive discussion of 
risks and possible benefits of participation will be provided to the participants and their families. Consent 
forms will be IRB-approved, and participants will be asked to read and review the document. The investigator 
will explain the research study to the participant and answer any questions that may arise. All participants 
will receive a verbal explanation suited to their comprehension of the purposes, procedures and potential 
risks as well as their rights as research participants. Participants will have the opportunity to carefully review 
the written consent form and ask questions prior to signing. The participants will have the opportunity to 
discuss the study with their surrogates or think about it prior to agreeing to participate. The participant will 
sign the informed consent document prior to any procedures being done specifically for the study. The 
participants may withdraw consent at any time throughout the course of the trial. A copy of the key 
information form document will be given to the participants for their records. The rights and welfare of the 
participants will be protected by emphasizing that the quality of their medical care will not be adversely 
affected if they decline to participate in this study. If possible, subjects will be given a copy of the informed 
consent form at their pre-surgical visit to allow them time to read through it, discuss with their relatives, and 
contact the study team with any questions prior to their surgery. 
 
A copy of the signed informed consent document will be given to the patient, placed in the patient’s 
electronic medical record and the original copy will be stored in the research regulatory binder.  Any 
alteration to the standard consent process (e.g., use of a translator, consent document presented orally, etc.) 
and the justification for such alteration will likewise be documented.  
 
Capacity will be assessed through the subject’s ability to express understanding of the information being 
presented to them. The subject will be asked to state back the goals of the study and that they are willing to 
participate in their primary language. 
3.5 Duration of Study Participation 
The study will remain open until 50 patients are recruited for each intervention arm of the study. The actual 
subject participation length will be seven days. 
3.6 Total Number of Participants and Sites  
Recruitment will end when 100 participants have been enrolled. It is expected that there will be subjects 
enrolled who will be lost to follow up and be evaluated by intention-to-treat. The sites for enrollment will be 
the NYU Langone Orthopedic Hospital and NYU Ambulatory Surgery Center at 38th street. 


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3.7 Participant Withdrawal or Termination 
Participants are free to withdraw from participation in the study at any time upon request. An investigator 
may terminate participation in the study if: 
• 
Any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant 
• 
The participant meets an exclusion criterion (either newly developed or not previously recognized) 
that precludes further study participation 
3.8 Premature Termination or Suspension of Study 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable cause. 
If the study is prematurely terminated or suspended, the PI will promptly inform the IRB and will provide 
the reason(s) for the termination or suspension. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants; 
• 
Demonstration of efficacy that would warrant stopping; 
• 
Insufficient compliance to protocol requirements; 
• 
Data that are not sufficiently complete and/or evaluable; or 
• 
Determination of futility 
4 Study Procedures and Schedule 
4.1 Study Procedures/Evaluations 
4.1.1 Study Specific Procedures 
Patients will be screened for eligibility by the surgical team during their pre-surgical office visit. Surgeons 
will explain the study to the eligible patient. 
 
If patients are agreeable to participation, a research team member will provide further details and ask for 
participation on day of surgery. Informed consent will be obtained on day of surgery when the patient is in 
the pre-operative holding room by an authorized research member. Patient will complete a baseline pain 
assessment as part of the research study.  
 
Patients in both the study and control group will receive the standard of care adductor canal block 
composed of 15 mL of bupivacaine (0.25%). Patients in the study group will receive the additional IPACK 
block performed using 20 mL of bupivacaine (0.25%) injected into the interspace between the popliteal 
artery and capsule of the knee. This use of bupivacaine (0.25%) in this dosage is consistent with its 
approved use for peripheral nerve blocks of the lower extremity, per the package insert. 
 
Postoperatively, pain will be assessed via visual analog scale (VAS) by nursing staff during the post-
operative period as per standard of care. The VAS pain scores are collected and documented in the patient’s 
electronic medical record. Additionally, while the patient is in the PACU, an authorized research member 
will visit the patient and administer a pain questionnaire (VAS and McGill Pain scale). Data on PACU opioid 
use documented in EPIC will be collected. 
4.1.2 Standard of Care Study Procedures 
The subjects receiving standard of care procedures will undergo adductor canal block with 15 mL of 0.25% 
bupivacaine. Although not standard of care at this institution, the addition of IPACK block is widely accepted 
as a standard part of multimodal analgesia in ACLR.  


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4.2 Study Schedule 
4.2.1 Screening  
 
Screening Visit (Pre-surgical office visit -30 to -1 days)  
• Review medical history to determine eligibility based on inclusion/exclusion criteria. 
• Review medications history to determine eligibility based on inclusion/exclusion criteria. 
• Provide participants with further details regarding their participation on day of surgery and follow up. 
 
4.2.2 Enrollment/Baseline 
 
Enrollment/Day of surgery (Visit 1, Day 0) 
• Obtain informed consent of potential participant verified by signature on study informed consent 
form. 
• Verify inclusion/exclusion criteria. 
• Complete baseline global health and pain assessment 
• Randomize to ACB or ACB + IPACK group 
• Perform surgery with analgesic intervention determined by randomization 
• Record vital signs, opioid usage, results of examinations, other pain assessments. 
• Continue observation in PACU preceding discharge, including administration of VAS scores, pain 
questionnaire, and opioid usage monitoring. 
4.2.3 Follow-Up Phone call/message (POD 1, POD 2 and POD 3) 
Phone call to patient to collect additional data on opioid use following discharge, on POD 1, POD 2 
and 3 after surgery 
4.2.4 Postoperative Visits 
Patients will present to postoperative visit #1 of POD 7 per standard of care, at which point VAS pain, 
ROM, and strength will be assessed.  
4.2.5 Withdrawal/Early Termination Visit 
Subjects may discontinue their participation in the study at any time. As there is only a single intervention, 
and the safety of this is not in question, further follow up will not be required if a subject decides to terminate 
their participation in the study. 
 
4.3 Concomitant Medications, Treatments, and Procedures 
 
All concomitant prescription medications taken during study participation will be recorded on the case 
report forms (CRFs). For this protocol, a prescription medication is defined as a medication that can be 
prescribed only by a properly authorized/licensed clinician. Medications to be reported in the CRF are 
concomitant prescription medications, over-the-counter medications and non-prescription medications. 
5 Risks and Benefits  
5.1 Potential risks  
Medication and Procedure 


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The potential risks associated with bupivacaine include neurologic and cardiac toxicity, if injected 
intravascularly. However, the risk is very low because a trained anesthesiologist using ultrasound guidance 
will perform both the IPACK block and ACB. US guidance allows the anesthesiologist to see and avoid blood 
vessels when administering the medication. Additionally, the syringe of the local anesthetic will be aspirated 
prior to injection by the anesthesiologist and surgeon to ensure that the block needle tip is not intravascular.  
 
The risk of nerve injury or intravascular injection in the IPACK block is similar to the standard ACB arm of the 
study. Risk of infection at the injection site due to the expertise of the anesthesiologist performing the block 
under ultrasound guidance under sterile conditions to avoid infection risk. Allergic reactions to local 
anesthetic is possible however, any subjects with a history of allergies to local anesthetic will be excluded 
from the study.  
 
At the time of the nerve block, the anesthesiologist who is providing the injection under ultrasound will 
monitor the subject’s vitals, respiratory and cardiac status to assess for the aforementioned risk of neurologic 
or cardiac toxicity, as suggested in the Bupivacaine package insert Subsequently, patients will be monitored 
in the post anesthesia care unit per standard of care for any adverse effects of the nerve block including 
nausea, vomiting, blurred vision, and infection at the injection site. Both the ACB and ACB plus IPACK block 
are used as standard of care at this institution depending on treatment physician’s preference.  
 
5.2 Potential benefits  
 
Study subjects may experience better pain control, improved satisfaction, decreased need for opioids and 
reduced incidence of side effects. If the study is not inconclusive, the study’s results may benefit future 
patients by showcasing that addition of IPACK block improves pain control in the first 24 hours of an ACLR. 
 
6 Statistical Analysis  
6.1 General Approach  
The primary analysis will follow the intention-to-treat (ITT) principle in order to evaluate the true outcome 
of the intervention as experienced by the patient who is blinded to the intervention. 
 
Continuous and categorical baseline characteristics will be compared using Hedges standardized difference 
Normally distributed data will be compared using t tests while non-normally distributed continuous 
outcomes will be assessed using the Mann-Whitney U test. 
 
It is anticipated that the data for some subjects will be incomplete for various reasons:  missing diary entries, 
refusal to answer a question on the questionnaire, onset of illness, loss-to-follow-up, etc. All occurrences of 
incomplete data will be investigated to carefully document the reasons for the missing data. If the primary 
outcome (amount of opioid utilization for the first 24 hours after surgery) cannot be ascertained with a 
reasonable degree of certainty, the patient will be excluded from the study. 
 
6.2 Analysis of Endpoints 
Primary Endpoints: 
1. Opioid utilization for the first 24 hours after surgery, including during surgery, calculated as oral 
morphine equivalent. 
 


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Secondary Endpoints: 
1. Patient reported VAS scores in PACU 
2. Length of stay in PACU 
3. Patient reported VAS scores on POD 1, POD 2, POD 3, POD7 
4. Reaction to IPACK block 
5. Mid-term functional outcomes will be assessed at 6 months: VAS, KOOS-PS, KUJALA, Tegner 
Activity Scale, strength, ROM.  
 
Normally distributed data such as the primary outcome variable will be compared using the two-sample t-
test. In the case that the data are not normally distributed, the Wilcoxon rank-sum test will be used instead. 
Categorical variable will be compared using the Chi-Squares unless other tests such as the Fisher’s exact test 
are more appropriate. 
 
All endpoints will be evaluated as fits the data set with graphical figures such as scatter plots, box-and-whisker 
plots, and frequency histograms to visualize the distribution of these outcomes and their relationships to 
covariates and treatment assignment. When appropriate descriptive graphical and tabular methods will also 
be estimated and presented in a graphical figure. 
 
6.2.1 
Baseline Descriptive Statistics 
The following patient data will be recorded: age, gender, height, weight, MRI diagnosis date of admission, date 
of discharge, laterality, surgical approach, implants used, duration of surgery, concomitant procedure, 
contamination, ASA, comorbidities (smoking, cardiac history, diabetes etc.), and medications. This 
information will be accessible in the patient’s medical record.  
6.3 Sample Size 
Using a 2-sided, 2-sample t test, an α value of 0.05, a power analysis revealed that 42 subjects were needed 
per group to detect a moderate effect size with a power of 0.80. We chose to enroll 50 subjects per arm to 
allow for potential dropout and an increased power. 
 
6.4 Enrollment/Randomization/Masking Procedures 
We will utilize randomization.com to generate a block randomization assignments for all 100 participants. 
Someone that is not a stakeholder in the study will make randomization envelopes, which include the study 
ID number, the treatment assignment, and dosage specifics. These randomization envelopes will then be 
distributed to the anesthesiologist pre-operatively by the authorized researcher after informed consent is 
obtained. 
6.5 Breaking the Study Blind/Participant Code 
If there is any adverse event related to the drug, we will break the blind for the subject and randomization will 
be disclosed to the patient. 
7 Assessment of Safety 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.  
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
• results in study withdrawal 
• is associated with a serious adverse event 
• is associated with clinical signs or symptoms 
• leads to additional treatment or to further diagnostic tests 
• is considered by the investigator to be of clinical significance 


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7.1 Definition of Adverse Events (AE) 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that is:  
• fatal 
• life-threatening 
• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 
• an important medical event 
 
Important medical events are those that may not be immediately life threatening but are clearly of major 
clinical significance. They may jeopardize the subject and may require intervention to prevent one of the 
other serious outcomes noted above. For example, drug overdose or abuse, a seizure that did not result in 
in-patient hospitalization, or intensive treatment of bronchospasm in an emergency department would 
typically be considered serious.  
 
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious 
adverse events.  
7.2 Definition of Unanticipated Problems (UP) 
 
Unanticipated Problems Involving Risk to Subjects or Others 
Any incident, experience, or outcome that meets all of the following criteria:  
• 
Unexpected in nature, severity, or frequency (i.e., not described in study-related documents such as 
the IRB-approved protocol or consent form, the investigators brochure, etc) 
• 
Related or possibly related to participation in the research (i.e., possibly related means there is a 
reasonable possibility that the incident experience, or outcome may have been caused by the 
procedures involved in the research) 
• 
Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
 
This definition could include an unanticipated adverse device effect, any serious adverse effect on health or 
safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of 
subjects (21 CFR 812.3(s)). 
 
7.3 Classification of an Adverse Event 
7.3.1 Severity of Event 
 
For AEs not included in the protocol defined grading system, the following guidelines will be used to 
describe severity. 
• Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities. 
• Moderate – Events result in a low level of inconvenience or concern with the therapeutic measures. 
Moderate events may cause some interference with functioning. 


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• Severe – Events interrupt a participant’s usual daily activity and may require systemic drug therapy 
or other treatment. Severe events are usually potentially life-threatening or incapacitating. 
 
7.3.2 Relationship to Study Agent 
 
The clinician’s assessment of an AE's relationship to study agent (drug, biologic, device) is part of the 
documentation process, but it is not a factor in determining what is or is not reported in the study. If there is 
any doubt as to whether a clinical observation is an AE, the event should be reported. All AEs must have their 
relationship to study agent assessed. In a clinical trial, the study product must always be suspect. To help assess, 
the following guidelines are used. 
 
1. Related – The AE is known to occur with the study agent, there is a reasonable possibility that the 
study agent caused the AE, or there is a temporal relationship between the study agent and event. 
Reasonable possibility means that there is evidence to suggest a causal relationship between the study 
agent and the AE. 
2. Not Related – There is not a reasonable possibility that the administration of the study agent caused 
the event, there is no temporal relationship between the study agent and event onset, or an alternate 
etiology has been established. 
 
For all collected AEs, the clinician who examines and evaluates the participant will determine the AE’s causality 
based on temporal relationship and his/her clinical judgment. The degree of certainty about causality will be 
graded using the categories below. 
 
1. Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test result, 
occurs in a plausible time relationship to drug administration and cannot be explained by concurrent 
disease or other drugs or chemicals. The response to withdrawal of the drug (dechallenge) should be 
clinically plausible. The event must be pharmacologically or phenomenologically definitive, with use of 
a satisfactory rechallenge procedure if necessary. 
2. Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within a 
reasonable time after administration of the drug, is unlikely to be attributed to concurrent disease or 
other drugs or chemicals, and follows a clinically reasonable response on withdrawal (dechallenge). 
Rechallenge information is not required to fulfill this definition. 
3. Possibly Related – There is some evidence to suggest a causal relationship (e.g., the event occurred 
within a reasonable time after administration of the trial medication). However, other factors may 
have contributed to the event (e.g., the participant’s clinical condition, other concomitant events). 
Although an AE may rate only as “possibly related” soon after discovery, it can be flagged as requiring 
more information and later be upgraded to “probably related” or “definitely related,” as appropriate. 
4. Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to drug administration makes a causal relationship improbable (e.g., the event 
did not occur within a reasonable time after administration of the trial medication) and in which other 
drugs or chemicals or underlying disease provides plausible explanations (e.g., the participant’s clinical 
condition, other concomitant treatments). 
5. Not Related – The AE is completely independent of study drug administration, and/or evidence exists 
that the event is definitely related to another etiology. There must be an alternative, definitive etiology 
documented by the clinician. 
 


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7.3.3 Expectedness 
The PI, Dr. Strauss, will be responsible for determining whether an AE is expected or unexpected. An AE will 
be considered unexpected if the nature, severity, or frequency of the event is not consistent with the risk 
information previously described for the study agent. 
 
7.4 Time Period and Frequency for Event Assessment and Follow-Up 
 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits and 
interviews of a study participant presenting for medical care, or upon review by a study monitor. All AEs 
including local and systemic reactions not meeting the criteria for SAEs will be captured on the appropriate 
RF. Information to be collected includes event description, time of onset, clinician’s assessment of severity, 
relationship to study product (assessed only by those with the training and authority to make a diagnosis), 
and time of resolution/stabilization of the event. All AEs occurring while on study must be documented 
appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any time 
during the study, it will be recorded as an AE. UPs will be recorded in the data collection system throughout 
the study. 
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event at 
each level of severity to be performed. AEs characterized as intermittent require documentation of onset 
and duration of each episode. 
 
The PI will record all reportable events with start dates occurring any time after informed consent is 
obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation. At each 
study visit, the investigator will inquire about the occurrence of AE/SAEs since the last visit. Events will be 
followed for outcome information until resolution or stabilization.  
 
All unresolved adverse events should be followed by the investigator until the events are resolved, the 
subject is lost to follow-up, or the adverse event is otherwise explained.  At the last scheduled visit, the 
investigator should instruct each subject to report any subsequent event(s) that the subject, or the subject’s 
personal physician, believes might reasonably be related to participation in this study.  The investigator 
should notify the study sponsor of any death or adverse event occurring at any time after a subject has 
discontinued or terminated study participation that may reasonably be related to this study.  The sponsor 
should also be notified if the investigator should become aware of the development of cancer or of a 
congenital anomaly in a subsequently conceived offspring of a subject that has participated in this study.  
 
7.5 Reporting Procedures – Notifying the IRB  
7.5.1 Unanticipated Problem Reporting 
 
Incidents or events that meet the OHRP criteria for UPs require the creation and completion of an UP report 
form. It is the site investigator’s responsibility to report UPs to their IRB. The UP report will include the 
following information: 
 
1. Protocol identifying information: protocol title and number, PI’s name, and the IRB project number; 
2. A detailed description of the event, incident, experience, or outcome; 


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3. An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP; 
4. A description of any changes to the protocol or other corrective actions that have been taken or are 
proposed in response to the UP. 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline: 
 
• 
UPs that are SAEs will be reported to the IRB within 7 days of the investigator becoming aware of 
the event. 
• 
Any other UP will be reported to the IRB within 7 days of the investigator becoming aware of the 
problem. 
• 
All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), the supporting agency head (or designee), and OHRP within 7 days 
of the IR’s receipt of the report of the problem from the investigator. 
7.6 Safety Oversight 
 
It is the responsibility of the Principal Investigator Eric J Strauss, and co-investigators David Furgiuele MD 
and Jovan Popovic MD to oversee the safety of the study at his/her site.  This safety monitoring will include 
careful assessment and appropriate reporting of adverse events as noted above, as well as the construction 
and implementation of a site data and safety-monitoring plan. Adverse Events such as development of an 
allergy to local anesthetic, inadvertent intravascular injection of local anesthetic and infection at site of 
injection will be reviewed every three months. Serious adverse events are rare and are unlikely to occur but 
if a serious adverse event occurs, steps will be taken to address it.  Study recruitment will cease temporarily 
while a data safety monitoring team convenes to review the event. Medical monitoring will include a regular 
assessment of the number and type of serious adverse events. 
 
Data Safety Monitoring Plan 
 
The principal investigator Eric J Strauss, and co-investigators David Furgiuele MD and Jovan Popovic MD are 
responsible for data safety and monitoring of the overall study.  
 
The following data points and outcomes will be reviewed during data safety monitoring reviews: number of 
patients enrolled, pain scores of patients, AEs and SAEs such as neuro and cardiotoxicity. Data will be 
monitored quarterly and will be reported at the time of continuing review.  
 
The stopping rules for the study are adverse harm to patients, as measured by the serious adverse events, 
specifically neurotoxicity, cardiotoxicity, or allergic reaction to bupivacaine. A chi-square test will be used to 
determine if there is a statistically significant difference (p<0.01) in the rate of SAEs between treatment 
arms. If there is a statistically significant difference in the rates of SAEs between arms, accrual to the trail 
will be suspended while the study team and data safety monitoring team conduct an evaluation of the 
events.  
 
The PI will oversee all study activities including data collection and management and will ensure study 
personnel conduct this study based on the approved protocol. 
8 Source Documents and Access to Source Data/Documents 
Source data is all information, original records of clinical findings, observations, or other activities in a 
clinical trial necessary for the reconstruction and evaluation of the trial.  Source data are contained in source 
documents.  Examples of these original documents, and data records include: hospital records, clinical and 


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office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing 
records, recorded data from automated instruments, copies or transcriptions certified after verification as 
being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, 
subject files, and records kept at the pharmacy, at the laboratories, and at medico-technical departments 
involved in the clinical trial. It is acceptable to use CRFs as source documents. If this is the case, it should be 
stated in this section what data will be collected on CRFs and what data will be collected from other sources. 
 
The study case report form (CRF) is the primary data collection instrument for the study.  All data requested 
on the CRF must be recorded.  All missing data must be explained.  If a space on the CRF is left blank because 
the procedure was not done or the question was not asked, write “N/D”.  If the item is not applicable to the 
individual case, write “N/A”.  All entries should be printed legibly in black ink.  If any entry error has been 
made, to correct such an error, draw a single straight line through the incorrect entry and enter the correct 
data above it.  All such changes must be initialed and dated.  DO NOT ERASE OR WHITE OUT ERRORS.  For 
clarification of illegible or uncertain entries, print the clarification above the item, then initial and date it. 
 
Access to study records and patient contact will be limited to IRB-approved study team members, not 
volunteers. The investigator will permit study-related monitoring, audits, and inspections by the IRB/EC, the 
sponsor, government regulatory bodies, and University compliance and quality assurance groups of all study 
related documents (e.g. source documents, regulatory documents, data collection instruments, study data 
etc.).  The investigator will ensure the capability for inspections of applicable study-related facilities (e.g. 
pharmacy, diagnostic laboratory, etc.). 
 
Participation as an investigator in this study implies acceptance of potential inspection by government 
regulatory authorities and applicable University compliance and quality assurance offices. 
9 Quality Assurance and Quality Control 
QC procedures will be implemented beginning with the data entry system and data QC checks that will be 
run on the database will be generated. Any missing data or data anomalies will be communicated to the 
site(s) for clarification/resolution. 
 
Following written SOPs, the monitors will verify that the clinical trial is conducted and data are generated, 
documented (recorded), and reported in compliance with the protocol, GCP, and the applicable regulatory 
requirements.  
10 Ethics/Protection of Human Subjects 
10.1 Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with Regulations for the 
Protection of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 
and/or the ICH E6. 
10.2 Institutional Review Board 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form must be 
obtained before any participant is enrolled. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. All changes to the consent form will 
be IRB approved; a determination will be made regarding whether previously consented participants need 
to be re-consented. 


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10.3 Participant and Data Confidentiality 
Information about study subjects will be kept confidential and managed according to the requirements of the 
Health Insurance Portability and Accountability Act of 1996 (HIPAA).  Those regulations require a signed 
subject authorization informing the subject of the following:  
• What protected health information (PHI) will be collected from subjects in this study 
• Who will have access to that information and why 
• Who will use or disclose that information  
• The rights of a research subject to revoke their authorization for use of their PHI.  
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, retains 
the ability to use all information collected prior to the revocation of subject authorization.  For subjects that 
have revoked authorization to collect or use PHI, attempts should be made to obtain permission to collect at 
least vital status (i.e. that the subject is alive) at the end of their scheduled study period. 
 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and the 
sponsor(s) and their agents. Therefore, the study protocol, documentation, data, and all other information 
generated will be held in strict confidence. No information concerning the study or the data will be released 
to any unauthorized third party without prior written approval of the sponsor. 
 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB or 
pharmaceutical company supplying study product may inspect all documents and records required to be 
maintained by the investigator, including but not limited to, medical records (office, clinic, or hospital) and 
pharmacy records for the participants in this study. The clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use during 
the study. At the end of the study, all records will continue to be kept in a secure location for as long a period 
as dictated by local IRB and Institutional regulations. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be 
transmitted to and stored at NYU Langone Medical Center. This will not include the participant’s contact or 
identifying information. Rather, individual participants and their research data will be identified by a unique 
study identification number. The study data entry and study management systems used by clinical sites and 
by NYU Langone Medical Center research staff will be secured and password protected. At the end of the study, 
all study databases will be de-identified and archived at the NYU Langone Medical Center. 
 
11 Data Handling and Record Keeping 
11.1 Data Collection and Management Responsibilities 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site PI. 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data 
reported. 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation of 
data. Black ink is required to ensure clarity of reproduced copies. When making changes or corrections, 
cross out the original entry with a single line, and initial and date the change. DO NOT ERASE, OVERWRITE, 
OR USE CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
 
Copies of the electronic CRF (eCRF) will be provided for use as source documents and maintained for 
recording data for each participant enrolled in the study. Data reported in the eCRF derived from source 


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This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
documents should be consistent with the source documents or the discrepancies should be explained and 
captured in a progress note and maintained in the participant’s official electronic study record. 
 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and clinical 
laboratory data will be entered into Redcap. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear inconsistent, incomplete, or 
inaccurate. Clinical data will be entered directly from the source documents. 
11.2 Study Records Retention 
Study documents will be retained for the longer of 3 years after close-out, 5 years after final 
reporting/publication. 
 
11.3 Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or Manual of Procedures 
(MOP) requirements. The noncompliance may be either on the part of the participant, the investigator, or 
the study site staff. As a result of deviations, corrective actions are to be developed by the site and 
implemented promptly. 
 
These practices are consistent with ICH E6: 
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
• 
5.1 Quality Assurance and Quality Control, section 5.1.1 
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2. 
 
It is the responsibility of the site PI/study staff to use continuous vigilance to identify and report deviations 
within 7 working days of identification of the protocol deviation, or within 7 working days of the scheduled 
protocol-required activity. 
 
Protocol deviations must be reported to the local IRB per their guidelines. The site PI/study staff is 
responsible for knowing and adhering to their IRB requirements. Further details about the handling of 
protocol deviations will be included in the MOP. 
 
11.4 Publication and Data Sharing Policy 
 
The International Committee of Medical Journal Editors (ICMJE) member journals have adopted a clinical 
trials registration policy as a condition for publication. The ICMJE defines a clinical trial as any research 
project that prospectively assigns human subjects to intervention or concurrent comparison or control 
groups to study the cause-and-effect relationship between a medical intervention and a health outcome. 
Medical interventions include drugs, surgical procedures, devices, behavioral treatments, process-of-care 
changes, and the like. Health outcomes include any biomedical or health-related measures obtained in 
patients or participants, including pharmacokinetic measures and adverse events. The ICMJE policy, and the 
Section 801 of the Food and Drug Administration Amendments Act of 2007, requires that all clinical trials be 
registered in a public trials registry such as ClinicalTrials.gov, which is sponsored by the National Library of 
Medicine. Other biomedical journals are considering adopting similar policies. For interventional clinical 
trials performed under NIH IC grants and cooperative agreements, it is the grantee’s responsibility to 
register the trial in an acceptable registry, so the research results may be considered for publication in 
ICMJE member journals. The ICMJE does not review specific studies to determine whether registration is 
necessary; instead, the committee recommends that researchers who have questions about the need to 


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This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
register err on the side of registration or consult the editorial office of the journal in which they wish to 
publish. 
 
FDAAA mandates that a "responsible party" (i.e., the sponsor or designated principal investigator) register 
and report results of certain "applicable clinical trials": 
 
• 
Trials of Drugs and Biologics: Controlled, clinical investigations, other than Phase I investigations of a 
product subject to FDA regulation; 
• 
Trials of Devices: Controlled trials with health outcomes of a product subject to FDA regulation (other 
than small feasibility studies) and pediatric postmarket surveillance studies. 
• 
NIH grantees must take specific steps to ensure compliance with NIH implementation of FDAAA. 
 
12 Study Finances 
12.1 Funding Source 
There is no funding source available.   
12.2 Costs to the Participant 
There are no expected costs to the subjects. 
12.3 Participant Reimbursements or Payments 
Participants will not receive any financial compensation for participation in this study. 
 
13 Conflict of Interest Policy 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a way 
that is appropriate to their participation in the trial. The study leadership has established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a mechanism 
for the management of all reported dualities of interest.  
 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial gain 
greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by the NYU 
Langone Conflict of Interest Management Unit (CIMU) with a Committee-sanctioned conflict management 
plan that has been reviewed and approved by the study sponsor prior to participation in this study. All 
NYULMC investigators will follow the applicable conflict of interest policies. 
 
 


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writing by the study sponsor 
14 References 
 
1. 
Bollen SR, Scott BW. Rupture of the anterior cruciate ligament--a quiet epidemic? Injury. Jul 
1996;27(6):407-9. doi:10.1016/0020-1383(96)00033-2 
2. 
Wilde J, Bedi A, Altchek DW. Revision anterior cruciate ligament reconstruction. Sports health. 
2014;6(6):504-518. doi:10.1177/1941738113500910 
3. 
Glogovac G, Schumaier AP, Grawe BM. Return to Sport Following Revision Anterior Cruciate Ligament 
Reconstruction 
in 
Athletes: 
A 
Systematic 
Review. 
Arthroscopy. 
Jul 
2019;35(7):2222-2230. 
doi:10.1016/j.arthro.2019.01.045 
4. 
Davey MS, Hurley ET, Anil U, et al. Pain Management Strategies After Anterior Cruciate Ligament 
Reconstruction: A Systematic Review With Network Meta-analysis. Arthroscopy. Apr 2021;37(4):1290-
1300.e6. doi:10.1016/j.arthro.2021.01.023 
5. 
Alaia MJ. Editorial Commentary: Uncle Sam Wants YOU! (to Stop the Opioid Crisis). Arthroscopy: The 
Journal 
of 
Arthroscopic 
& 
Related 
Surgery. 
2020-03-01 
2020;36(3):832-833. 
doi:10.1016/j.arthro.2019.12.021 
6. 
Kim DH, Lin Y, Goytizolo EA, et al. Adductor Canal Block versus Femoral Nerve Block for Total Knee 
Arthroplasty. Anesthesiology. 2014-03-01 2014;120(3):540-550. doi:10.1097/aln.0000000000000119 
7. 
Lynch JR, Okoroha KR, Lizzio V, Yu CC, Jildeh TR, Moutzouros V. Adductor Canal Block Versus Femoral 
Nerve Block for Pain Control After Anterior Cruciate Ligament Reconstruction: A Prospective Randomized 
Trial. Am J Sports Med. Feb 2019;47(2):355-363. doi:10.1177/0363546518815874 
8. 
Xue Q, Jiang W, Wang M, Sui J, Wang Y. Femoral nerve block vs adductor canal block after anterior 
cruciate ligament reconstruction under general anesthesia: A prospective randomized trial protocol. Medicine. 
2020;99(28):e20776-e20776. doi:10.1097/MD.0000000000020776 
9. 
Abdallah FW, Chan VWS, Gandhi R, Koshkin A, Abbas S, Brull R. The Analgesic Effects of Proximal, 
Distal, or No Sciatic Nerve Block on Posterior Knee Pain after Total Knee Arthroplasty. Anesthesiology. 2014-
12-01 2014;121(6):1302-1310. doi:10.1097/aln.0000000000000406 
10. 
Patterson ME, Vitter J, Bland K, Nossaman BD, Thomas LC, Chimento GF. The Effect of the IPACK Block 
on Pain After Primary TKA: A Double-Blinded, Prospective, Randomized Trial. The Journal of Arthroplasty. 
2020-06-01 2020;35(6):S173-S177. doi:10.1016/j.arth.2020.01.014 
11. 
Ochroch J, Qi V, Badiola I, et al. Analgesic efficacy of adding the IPACK block to a multimodal analgesia 
protocol for primary total knee arthroplasty. Reg Anesth Pain Med. Oct 2020;45(10):799-804. 
doi:10.1136/rapm-2020-101558 
12. 
Schwenk ES, Gupta RK. Femoral triangle block plus iPACK block versus local infiltration analgesia for 
anterior cruciate ligament reconstruction: an infographic. Regional Anesthesia & Pain Medicine. 2022-01-01 
2022;47(1):64-64. doi:10.1136/rapm-2021-102942 
 
 
 


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CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in 
writing by the study sponsor 
15 Attachments 
These documents are relevant to the protocol, but they are not considered part of the protocol.  They are 
stored and modified separately. As such, modifications to these documents do not require protocol 
amendments. 
15.1 MORPHINE EQUIVALENTS