Pain After Total Knee Arthroplasty: a Comparison of Combined Continuous Adductor Canal Block With Infiltration of Local Anesthetic Between the Popliteal Artery and Capsule of the Knee Block Versus Continuous Adductor Canal Block Alone on Postoperative Analgesia
Phase: PHASE4
Conditions: Arthropathy of Knee, Anesthesia
Sponsor: Ochsner Health System

 
Ochsner Clinic Foundation 
Ochsner Health System 
 
 
 
 
 
 
 
Pain after total knee arthroplasty: a comparison of combined 
continuous adductor canal block with infiltration of local anesthetic 
between the popliteal artery and capsule of the knee block versus 
continuous adductor canal block alone on postoperative analgesia 
 
 
Regulatory Sponsor: 
None 
Funding Sponsor: 
None, internal funding 
Study Product: 
PRO 00013121 
Protocol Number: 
2016.307.c 
IND Number: 
Not applicable 
 
 
 
 
 
Date: November 17, 2016 
 
Amended: N/A 
 
Administrative Change: N/A 
 
 
 
CONFIDENTIAL 
 
This document is confidential and the property of the Ochsner Clinic Foundation.  No part 
of it may be transmitted, reproduced, published, or used by other persons without prior 
written authorization from the study sponsor. 

 
 
Page ii 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
Table of Contents 
STUDY SUMMARY ................................................................................................................................................... 1 
1 
INTRODUCTION .............................................................................................................................................. 3 
1.1 
BACKGROUND .................................................................................................................................................. 3 
1.2 
INVESTIGATIONAL AGENT................................................................................................................................ 4 
1.3 
PRECLINICAL DATA ......................................................................................................................................... 4 
1.4 
CLINICAL DATA TO DATE ................................................................................................................................ 4 
1.5 
DOSE RATIONALE AND RISK/BENEFITS ............................................................................................................ 4 
2 
STUDY OBJECTIVES ...................................................................................................................................... 4 
3 
STUDY DESIGN ................................................................................................................................................ 4 
3.1 
GENERAL DESIGN ............................................................................................................................................ 4 
3.2 
PRIMARY STUDY ENDPOINTS ........................................................................................................................... 5 
3.3 
SECONDARY STUDY ENDPOINTS ...................................................................................................................... 5 
3.4 
PRIMARY SAFETY ENDPOINTS .......................................................................................................................... 5 
4 
SUBJECT SELECTION AND WITHDRAWAL............................................................................................ 5 
4.1 
INCLUSION CRITERIA ....................................................................................................................................... 5 
4.2 
EXCLUSION CRITERIA ...................................................................................................................................... 6 
4.3 
SUBJECT RECRUITMENT AND SCREENING ........................................................................................................ 6 
4.4 
EARLY WITHDRAWAL OF SUBJECTS ................................................................................................................. 6 
4.4.1 
When and How to Withdraw Subjects .................................................................................................... 6 
4.4.2 
Data Collection and Follow-up for Withdrawn Subjects ....................................................................... 6 
5 
STUDY DRUG ................................................................................................................................................... 6 
5.1 
DESCRIPTION ................................................................................................................................................... 6 
5.2 
TREATMENT REGIMEN ..................................................................................................................................... 6 
5.3 
METHOD FOR ASSIGNING SUBJECTS TO TREATMENT GROUPS ......................................................................... 7 
5.4 
PREPARATION AND ADMINISTRATION OF STUDY DRUG ................................................................................... 7 
5.5 
SUBJECT COMPLIANCE MONITORING ............................................................................................................... 7 
5.6 
PRIOR AND CONCOMITANT THERAPY .............................................................................................................. 7 
5.7 
PACKAGING...................................................................................................................................................... 7 
5.8 
BLINDING OF STUDY DRUG .............................................................................................................................. 7 
5.9 
RECEIVING, STORAGE, DISPENSING AND RETURN ............................................................................................ 7 
5.9.1 
Receipt of Drug Supplies ....................................................................................................................... 7 
5.9.2 
Storage ................................................................................................................................................... 7 
5.9.3 
Dispensing of Study Drug ...................................................................................................................... 8 
5.9.4 
Return or Destruction of Study Drug ..................................................................................................... 8 
6 
STUDY PROCEDURES .................................................................................................................................... 8 
6.1 
DAY OF SURGERY (POD #0) ............................................................................................................................ 8 
6.2 
POSTOPERATIVE COURSE ................................................................................................................................. 9 
7 
STATISTICAL PLAN ....................................................................................................................................... 9 
7.1 
SAMPLE SIZE DETERMINATION ........................................................................................................................ 9 
7.2 
STATISTICAL METHODS ................................................................................................................................... 9 
7.3 
SUBJECT POPULATION(S) FOR ANALYSIS ......................................................................................................... 9 
8 
SAFETY AND ADVERSE EVENTS ............................................................................................................... 9 
8.1 
DEFINITIONS .................................................................................................................................................... 9 
8.2 
RECORDING OF ADVERSE EVENTS ................................................................................................................. 11 
8.3 
REPORTING OF SERIOUS ADVERSE EVENTS.................................................................................................... 12 
8.3.1 
Study Sponsor Notification by Investigator ......................................................................................... 12 
8.3.2 
EC/IRB Notification by Investigator .................................................................................................... 12 
8.3.3 
FDA Notification by Sponsor ............................................................................................................... 12 

 
 
Page iii 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
8.4 
UNBLINDING PROCEDURES ............................................................................................................................ 13 
8.5 
STOPPING RULES ............................................................................................................................................ 13 
8.6 
MEDICAL MONITORING.................................................................................................................................. 13 
8.6.1 
Internal Data and Safety Monitoring Board ........................................................................................ 13 
8.6.2 
Independent Data and Safety Monitoring Board ................................................................................. 13 
9 
DATA HANDLING AND RECORD KEEPING .......................................................................................... 13 
9.1 
CONFIDENTIALITY .......................................................................................................................................... 13 
9.2 
SOURCE DOCUMENTS ..................................................................................................................................... 14 
9.3 
CASE REPORT FORMS..................................................................................................................................... 14 
9.4 
RECORDS RETENTION .................................................................................................................................... 14 
10 
STUDY MONITORING, AUDITING, AND INSPECTING ....................................................................... 14 
10.1 
STUDY MONITORING PLAN ....................................................................................................................... 14 
10.2 
AUDITING AND INSPECTING ....................................................................................................................... 14 
11 
ETHICAL CONSIDERATIONS .................................................................................................................... 15 
12 
STUDY FINANCES ......................................................................................................................................... 15 
12.1 
FUNDING SOURCE ..................................................................................................................................... 15 
12.2 
CONFLICT OF INTEREST ............................................................................................................................. 15 
12.3 
SUBJECT STIPENDS OR PAYMENTS ............................................................................................................ 15 
13 
PUBLICATION PLAN .................................................................................................................................... 15 
14 
REFERENCES ................................................................................................................................................. 16 
15 
ATTACHMENTS ............................................................................................................................................ 16 
 

 
 
Page iv 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
List of Abbreviations 
 
ACB – adductor canal block 
IPACK – infiltration between the popliteal artery and capsule of the knee 
FNB – femoral nerve block 
TKA – total knee arthroplasty 
PACU – post anesthesia recovery unit 
DOSC – day of surgery center (preoperative area) 
IV – intravenous 
PO – per os (oral) 
RASS – Richmond agitation sedation score 
BPI – brief pain inventory 
 
 
 
 

 
 
Page 1 
Study Summary 
Title 
Pain after total knee arthroplasty: a comparison of combined 
continuous adductor canal block with infiltration of local anesthetic 
between the popliteal artery and capsule of the knee block versus 
continuous adductor canal block alone on postoperative analgesia 
Short Title 
IPACK nerve block for total knee arthroplasty 
Protocol Number 
N/A 
Phase 
IV 
Methodology 
Allocation: Randomized 
Endpoint Classification: Efficacy Study 
Intervention Model: Single Group Assignment 
Masking: Double Blind (Outcomes Assessor, patient) 
Primary Purpose: Treatment 
Study Duration 
Intervention period immediately prior to surgery with follow-up until 
hospital discharge 
Study Center(s) 
Ochsner Medical Center Main Campus 
Objectives 
To examine the effect of two approaches to nerve blockade on opioid 
consumption, patient satisfaction, postoperative pain, mobility, length 
of hospital stay, and several other secondary outcomes. 
Number of Subjects 
72 total, approximately 36 in each study arm 
Diagnosis and Main 
Inclusion Criteria 
Inclusion Criteria: 
• Unilateral, primary tricompartment total knee arthroplasty 
• Age 18 years or older 
• ASA I-III 
• Eligible for spinal or combined spinal epidural anesthetic 
• Able to speak, read, and understand English 
• Willing to participate in the trial 
• Anticipated discharge home from hospital 
 
Exclusion Criteria: 
• Contraindication to regional anesthesia or peripheral nerve 
blocks 
• Allergy to local anesthetics 
• Allergy to NSAIDs 
• Chronic renal insufficiency with Cr > 1.4 or GFR < 60 
• Have chronic pain that is not related to their knee joint 
• Have been using opioids on a chronic basis (daily or almost 
daily opioid use for 3 months or longer) 
• Have a pre-existing peripheral neuropathy involving the 
operative site 
• Body mass index greater than 40 

 
 
Page 2 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
Study Regimen 
Double-blind, randomized controlled clinical trial to test the efficacy of 
IPACK on postoperative opioid consumption, patient satisfaction, pain 
scores, mobility, and several other secondary outcomes in adults 
undergoing primary unilateral TKA. 
Enrolled patients will be randomized to either continuous ACB with 
IPACK or to continuous ACB with sham subcutaneous saline injection.  
Outcomes assessors and patients will be blinded to the intervention. 
Duration of 
administration 
Single preoperative IPACK block 
Reference therapy 
No IPACK block/sham subcutaneous saline injection 
Statistical 
Methodology 
Descriptive statistics per Ochsner statisticians 
 

 
 
Page 3 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
1 Introduction 
This document is a protocol for a human research study. This study is to be conducted according 
to US and international standards of Good Clinical Practice (FDA Title 21 part 312 and 
International Conference on Harmonization guidelines), applicable government regulations and 
Institutional research policies and procedures.  
1.1 Background 
Total knee arthroplasty (TKA) is an effective surgical treatment for end-stage knee osteoarthritis 
and is commonly performed in the United States.  Recovery following TKA is painful and 
regional anesthesia is often utilized to minimize postoperative pain, improve function, and allow 
earlier rehabilitation physical therapy.  Goals of regional anesthesia are to provide effective 
analgesia with minimal postoperative muscle weakness to allow for early postoperative 
rehabilitation while also minimizing fall risk in the immediate postoperative period.  While many 
different regional modalities exist and are effective for improving pain control, there is no 
consensus for best technique.  Popular regional techniques for postoperative analgesia include 
single injection or continuous femoral nerve block (FNB) and adductor canal block (ACB), 
sciatic nerve block (SNB), and lumbar epidurals.  Each modality requires a technical skill set and 
has its own limitations, benefits, and risk profile.  Interestingly, a study in 2014 showed that 
approximately 76% of TKA surgeries across the country are still performed under general 
anesthesia and 87% of these patients do not receive any regional technique, despite 
overwhelming evidence of improved patient outcomes, decreased length of hospital stay, and 
improved function with regional techniques.1  More recently, a 2016 study showed that only 
27.3% of patients in a national registry received a peripheral nerve block and this was associated 
with decreased extended-length recovery room stays and postoperative nausea and/or vomiting.2 
 
Recent studies published, including one study performed at Ochsner Medical Center,5 support 
that ACB provides similar analgesia compared to FNB while preserving straight leg raise and 
sparing the majority of quadriceps motor function.3,4,5  Both ACB and FNB only provide 
analgesia to the anterior medial part of the knee and most tricompartment TKA patients require 
supplemental opioid medications to cover joint pain usually attributed to the sciatic and obturator 
nerves.  Historically SNB was used effectively to provide posterior analgesia but now is less 
used due to concern over increased difficulty with physical therapy due to foot drop.  Because 
peroneal nerve palsy occurs in 0.3-1.3% of TKA,6 an additional concern is that foot drop due to 
SNB may mask surgical injury to the common peroneal nerve. 
 
A novel alternative to SNB is the infiltration of local anesthetic between the popliteal artery and 
capsule of the knee (IPACK) block that targets the terminal sensory nerve endings to the 
posterior knee joint.  Common practice at our institution incorporates preoperative continuous 
ACB and single IPACK block.  A retrospective review of patients at our institution who received 
IPACK block with continuous FNB compared to patients who received FNB alone showed 
similar VAS pain scores with significantly decreased narcotic requirements postoperatively.  The 
same retrospective review showed that patients who received IPACK block with continuous 
ACB had clinically improved performance with physical therapy and a significantly shorter 
hospital stay.7  The goal of this study is to prospectively examine and hopefully confirm the 
observations of the retrospective chart review by studying the effect of preoperative IPACK 

 
 
Page 4 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
block on opioid consumption, patient satisfaction, pain scores, walk distance, hospital length of 
stay, and several other secondary outcomes. 
1.2 Investigational Agent 
Infiltration of local anesthetic between the popliteal artery and capsule of the knee (IPACK) 
block using 20ml of ropivacaine 0.25% with 1:300,000 epinephrine. 
1.3 Preclinical Data 
N/A 
1.4 Clinical Data to Date 
No published studies about IPACK exist.  An IRB-approved retrospective review of patients at 
our institution who received IPACK with continuous FNB compared to patients who received 
FNB alone showed similar VAS pain scores with significantly decreased narcotic requirements 
postoperatively.6  The group of patients who received IPACK block had a 38.8% decrease in the 
mean opioid consumption in the first 24 hours.  The same retrospective review showed that 
patients who received IPACK with continuous ACB had clinically improved performance with 
physical therapy and a significantly shorter hospital stay. 
1.5 Dose Rationale and Risk/Benefits 
We chose 20ml of 0.25% ropivacaine with 1:300,000 epinephrine to use for the IPACK because 
under ultrasound guidance it appears to provide adequate spread without reaching the sciatic 
nerve and causing foot drop.  Less volume may not reliably provide analgesia.  Larger volumes 
could cause foot drop or even lead to anesthetic toxicity. 
 
2 Study Objectives 
The goal of this study is to prospectively examine the effect of preoperative IPACK block on 
opioid consumption, patient satisfaction, pain scores, walk distance, hospital length of stay, and 
several other secondary outcomes. 
3 Study Design 
3.1 General Design 
Double blinded, randomized controlled trial.  All patients who present for primary, unilateral 
tricompartment TKA will be screened for inclusion.  Consecutive patients who meet preset 
inclusion and exclusion criteria will be recruited either on day of surgery or in the preoperative 
anesthesia clinic by one of the study investigators.  Written consent will be obtained for study 
participation.  Patients who participate will be randomized into one of two treatment arms: 
continuous ACB with IPACK block versus continuous ACB with sham subcutaneous saline 
injection.  Randomization will be done using the website random.org’s Coin Flipper, selecting 
the Susan B Anthony coin, and flipping 5 coins.  Majority heads will be randomized to receive 
the IPACK block whereas majority tails will be randomized to receive the sham subcutaneous 
injection.  See Attachment A for an example of this website. 
 

 
 
Page 5 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
Only the regional anesthesiologist performing the block will know the randomization status.  The 
study participants, outcome assessors/researchers, other anesthesia personnel, surgeons, 
physician assistants, and nurses will be blinded to the treatment arm.  All patients will receive 
sedation with midazolam and/or fentanyl titrated to comfort during block procedures.  Per our 
standard practice at Ochsner Medical Center, all patients will have either spinal or combined 
spinal-epidural anesthesia with mepivacaine 1.5% as the primary anesthetic during the surgery 
and sedation with propofol titrated to comfort.  Also per our standard practice at Ochsner 
Medical Center, multimodal therapy will include ketamine 0.25mg/kg IV (up to 50mg) 
intraoperatively, dexamethasone 8mg IV intraoperatively, pregablin 150mg PO preoperatively 
(adjusted to 75mg for age over 70) followed by 75mg nightly (or home gabapentin dose), 
acetaminophen 1000mg IV followed by 100mg PO every 6 hours postoperatively, and celecoxib 
400mg PO on POD #0 followed by 200mg PO daily. 
3.2 Primary Study Endpoints 
• Cumulative opioid consumption (morphine equivalents) in the first 24 hours 
3.3 Secondary Study Endpoints 
• Patient satisfaction on day of discharge using the Brief Pain Inventory (BPI) or a similar 
validated satisfaction survey 
• Average pain score at rest and with physical therapy in PACU, POD#1 am, POD#1 pm 
• Worst pain score at rest and with physical therapy in PACU, POD#1 am, POD#1 pm 
• Walk distance on POD#1 am, POD#1 pm, POD#2 
• Time to first intravenous opioid, oral opioid in PACU and after arrival to hospital room 
• Time to oral-only opioids 
• Pain location 
• Hospital length of stay 
• Incidence of foot drop 
• Incidence of itching, nausea, or vomiting in PACU, POD#1am, POD#1 pm 
• Incidence of over-sedation based on Richmond Agitation Sedation (RASS) score 
3.4 Primary Safety Endpoints 
Not applicable. 
4 Subject Selection and Withdrawal 
4.1 Inclusion Criteria 
• Unilateral, primary tricompartment total knee arthroplasty 
• Age 18 years or older 
• ASA I-III 
• Eligible for spinal or combined spinal epidural anesthetic 
• Able to speak, read, and understand English 
• Willing to participate in the trial 

 
 
Page 6 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
4.2 Exclusion Criteria 
• Contraindication to regional anesthesia or peripheral nerve blocks 
• Allergy to local anesthetics 
• Allergy to NSAIDs 
• Chronic renal insufficiency with Cr > 1.4 or GFR < 60 
• Have chronic pain that is not related to their knee joint 
• Have been using opioids on a chronic basis (daily or almost daily opioid use for 3 months 
or longer) 
• Have a pre-existing peripheral neuropathy involving the operative site 
• Body mass index greater than or equal to 40 
4.3 Subject Recruitment and Screening 
All patients scheduled for primary unilateral TKA at Ochsner Medical Center Main Campus will 
be screened for eligibility.  Eligible patients will be provided study information by one of the 
study investigators on day of surgery or in preoperative anesthesia clinic and given option to 
participate in the study.  Participants will undergo written consent.  There is no financial 
inventive for participation. 
4.4 Early Withdrawal of Subjects 
4.4.1 When and How to Withdraw Subjects 
Patients may voluntarily withdraw at any time of the study.  All procedures are performed 
preoperatively and further patient participation only includes questionnaires while admitted to 
the hospital.  Patients may refuse to answer these questionnaires.  Patients may also elect to 
discontinue their continuous ACB early. 
4.4.2 Data Collection and Follow-up for Withdrawn Subjects 
All withdrawn subjects will be included in the intention to treat analysis.  Already-accrued data 
for individuals who withdraw from the study will be maintained as part of the study data. 
5 Study Drug  
5.1 Description 
Peripheral nerve blocks will be performed using preservative-free ropivacaine 0.25% with 
1:300,000 epinephrine.  Dilutions and sham subcutaneous injections will use preservative-free 
0.9% saline.  Package inserts are included as Attachment C. 
5.2 Treatment Regimen 
Two treatment regimens exist: 1) continuous ACB and IPACK block both with ropivacaine 
0.25% with 1:300,000 epinephrine; and 2) continuous ACB with ropivacaine 0.25% with 
1:300,000 epinephrine and sham subcutaneous saline injection. 

 
 
Page 7 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
5.3 Method for Assigning Subjects to Treatment Groups 
Subjects will be randomized to one treatment arm at time of trial enrollment.  Randomization 
will be done using the website random.org’s Coin Flipper, selecting the Susan B Anthony coin, 
and flipping 5 coins.  Majority heads will be randomized to receive the IPACK block whereas 
majority tails will be randomized to receive the sham subcutaneous injection. 
5.4 Preparation and Administration of Study Drug 
Preservative-free ropivacaine 0.25% with 1:300,000 epinephrine will be prepared on day of 
surgery by diluting ropivacaine 0.5% with sterile saline and adding the appropriate amount of 
epinephrine.  A total of 20ml will be used during adductor canal catheter placement and 20ml 
will be used in the IPACK block.  All drug preparations will be performed by a member of the 
regional anesthesia team. 
5.5 Subject Compliance Monitoring 
Study investigators will ensure that correct multimodal therapy is ordered and review the 
medication record to ensure appropriate administration by nursing. 
5.6 Prior and Concomitant Therapy 
Patients taking opioid medications daily or almost daily for 3 months or greater preoperatively 
will not be included in this study. 
5.7 Packaging 
Not applicable. 
5.8 Blinding of Study Drug 
Physicians performing the study intervention will not be blinded to the drug or technique.  
Outcome assessors and patients will be blinded to the study intervention performed. 
5.9 Receiving, Storage, Dispensing and Return 
5.9.1 Receipt of Drug Supplies 
Upon receipt of the of the study treatment supplies, an inventory must be performed and a 
drug receipt log filled out and signed by the person accepting the shipment.  It is important 
that the designated study staff counts and verifies that the shipment contains all the items 
noted in the shipment inventory.  Any damaged or unusable study drug in a given shipment 
(active drug or comparator) will be documented in the study files.  The investigator must 
notify study sponsor of any damaged or unusable study treatments that were supplied to the 
investigator’s site. 
5.9.2 Storage 
Study drugs are securely stored in the pyxis and regional anesthesia block cart. 

 
 
Page 8 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
5.9.3 Dispensing of Study Drug 
Study drugs will be dispensed from the pyxis and regional anesthesia block cart by a 
member of the regional anesthesia team on day of surgery.  
5.9.4 Return or Destruction of Study Drug 
At the completion of the study, there will be a final reconciliation of drug shipped, drug 
consumed, and drug remaining.  This reconciliation will be logged on the drug reconciliation 
form, signed and dated.  Any discrepancies noted will be investigated, resolved, and 
documented prior to return or destruction of unused study drug.  Drug destroyed on site will 
be documented in the study files. 
6 Study Procedures 
6.1 Day of Surgery (POD #0) 
Prior to regional interventions, patients will be placed on standard ASA monitors with EtCO2 
monitoring and supplemental oxygen by nasal cannula.  A time out will be performed with the 
regional team, pre-op nurse, and patient prior to any sedating medications.  Sedation will be 
accomplished with midazolam and fentanyl titrated to patient comfort at the discretion of the 
regional team. 
 
Continuous adductor canal block placement 
A high-frequency linear ultrasound transducer will be used to identify the adductor canal.  The 
transducer will be placed at the mid-thigh, approximately half the distance between the inguinal 
crease and the patella, and at least 12 cm above the patella.  The superficial femoral artery will 
be identified when it courses dorsal/lateral to the sartorius muscle in the short-axis.  The 
hyperechoic structure located lateral/anterior to the artery will be the target catheter site at the 
adductor canal.  A 17-gauge Tuohy needle will be placed lateral to the superficial femoral artery 
and within the adductor canal, using an in-plane ultrasound technique by a member of the 
regional anesthesia team.  A total of 20ml of local anesthesia will be injected into the adductor 
canal.  A flexible spring-wound 19-gauge epidural catheter will be advanced 1-2 cm into the 
adductor canal.  The needle will be removed and a test dose of 5ml lidocaine 1.5% with 
1:200,000 epinephrine will be injected into the catheter under ultrasound observation.  The 
continuous catheter will be secured with surgical glue and liquid adhesive, and covered with a 
clear occlusive dressing.  The catheter will be attached to a portable electronic infusion pump 
when the patient reaches PACU.  In PACU, an initial 5ml bolus and then 8ml/h continuous 
infusion of ropivacaine 0.2% will be initiated through the continuous adductor canal catheter. 
 
IPACK block placement 
A high-frequency curvilinear ultrasound transducer will be used to identify the popliteal artery 
just proximal to the femoral condyles along the shaft of the femur in the short-axis.  A 21g 
peripheral nerve block needle will be advanced using an in-plane ultrasound technique until the 
needle tip is located between the popliteal artery and femoral shaft.  A total of 15ml of local 
anesthesia will be injected at this location with an additional 5ml of local anesthesia injected as 
the needle is withdrawn. 
 
 

 
 
Page 9 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
Sham subcutaneous saline injection 
A high-frequency curvilinear ultrasound transducer will be used to identify the popliteal artery 
just proximal to the femoral condyles along the shaft of the femur in the short-axis as done with 
the IPACK block.  A total of 1-2 ml of saline will be injected subcutaneously through a 
peripheral nerve block needle.   
6.2 Postoperative Course 
No further procedures are required. 
 
At 24 hours, the cumulative opioid consumption will be summated.  An outcomes assessor will 
survey the patient at pre-specified times for secondary outcomes.  Additional secondary 
outcomes will be pulled from the electronic medical record.  
 
Per standard of care at Ochsner Medical Center, patients that meet clinical milestones will be 
discharged home on the afternoon of POD#1 with an on-Q pain ball that will be removed by the 
patient after approximately 48 hours. 
7 Statistical Plan 
7.1 Sample Size Determination 
Prior published literature demonstrates analgesic equivalence between adductor canal block and 
femoral nerve block.3,4  An institutional retrospective study here showed a 38.8% effect 
difference between femoral nerve block with and without IPACK.  Using this information, for an 
effect size of 0.4, power of 0.8, and significance level of 0.05 we determined a sample size of 64 
patients.  Assuming a dropout rate of 10%, we will include 72 patients in this study with 
approximately 36 patients per study arm. 
7.2 Statistical Methods 
A t-test will be used to compare the two arms of the study.  We will apply other statistical 
methods as per Ochsner’s statistics team & researchers. 
7.3 Subject Population(s) for Analysis 
• Unilateral, primary tricompartment total knee arthroplasty 
• Age 18 years or older 
• ASA I-III 
• Eligible for spinal or combined spinal epidural anesthetic 
• Able to speak, read, and understand English 
• Willing to participate in the trial 
• Do not meet any exclusion criteria previously defined in this protocol 
8 Safety and Adverse Events 
8.1 Definitions 
Adverse Event 

 
 
Page 10 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
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 
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.  
Adverse Event Reporting Period 
The study period during which adverse events must be reported is normally defined as the 
period from the initiation of any study procedures to the end of the study treatment follow-
up.  For this study, the study treatment follow-up is defined as 30 days following the last 
administration of study treatment.  
Preexisting Condition 
A preexisting condition is one that is present at the start of the study.  A preexisting 
condition should be recorded as an adverse event if the frequency, intensity, or the 
character of the condition worsens during the study period. 
General Physical Examination Findings 
At screening, any clinically significant abnormality should be recorded as a preexisting 
condition.  At the end of the study, any new clinically significant findings/abnormalities 
that meet the definition of an adverse event must also be recorded and documented as an 
adverse event.  
Post-study Adverse Event 

 
 
Page 11 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
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.  
Abnormal Laboratory Values 
A clinical laboratory abnormality should be documented as an adverse event if any one of 
the following conditions is met:  
• The laboratory abnormality is not otherwise refuted by a repeat test to confirm the 
abnormality 
• The abnormality suggests a disease and/or organ toxicity 
• The abnormality is of a degree that requires active management; e.g. change of 
dose, discontinuation of the drug, more frequent follow-up assessments, further 
diagnostic investigation, etc. 
Hospitalization, Prolonged Hospitalization or Surgery 
Any adverse event that results in hospitalization or prolonged hospitalization should be 
documented and reported as a serious adverse event unless specifically instructed otherwise 
in this protocol.  Any condition responsible for surgery should be documented as an 
adverse event if the condition meets the criteria for and adverse event.  
 
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported 
as an adverse event in the following circumstances: 
• Hospitalization or prolonged hospitalization for diagnostic or elective surgical 
procedures for a preexisting condition.  Surgery should not be reported as an 
outcome of an adverse event if the purpose of the surgery was elective or diagnostic 
and the outcome was uneventful. 
• Hospitalization or prolonged hospitalization required to allow efficacy 
measurement for the study. 
• Hospitalization or prolonged hospitalization for therapy of the target disease of the 
study, unless it is a worsening or increase in frequency of hospital admissions as 
judged by the clinical investigator. 
8.2 Recording of Adverse Events 
At each contact with the subject, the investigator must seek information on adverse events by 
specific questioning and, as appropriate, by examination.  Information on all adverse events 
should be recorded immediately in the source document, and also in the appropriate adverse 
event module of the case report form (CRF).  All clearly related signs, symptoms, and abnormal 
diagnostic procedures results should recorded in the source document, though should be grouped 
under one diagnosis. 

 
 
Page 12 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
 
All adverse events occurring during the study period must be recorded.  The clinical course of 
each event should be followed until resolution, stabilization, or until it has been determined that 
the study treatment or participation is not the cause.  Serious adverse events that are still ongoing 
at the end of the study period must be followed up to determine the final outcome.  Any serious 
adverse event that occurs after the study period and is considered to be possibly related to the 
study treatment or study participation should be recorded and reported immediately. 
8.3 Reporting of Serious Adverse Events 
8.3.1 Study Sponsor Notification by Investigator 
A serious adverse event must be reported to the study sponsor by telephone within 24 hours 
of the event.  A Serious Adverse Event (SAE) form must be completed by the investigator 
and faxed to the study sponsor within 24 hours.  The investigator will keep a copy of this 
SAE form on file at the study site.  Report serious adverse events by phone and facsimile 
to: 
 
Matthew Patterson,     phone 504-842-3755,     fax 504-842-2036 
 
At the time of the initial report, the following information should be provided: 
• Study identifier 
• Study Center 
• Subject number 
• A description of the event 
• Date of onset 
• Current status 
• Whether study treatment was 
discontinued 
• The reason why the event is 
classified as serious 
• Investigator assessment of the 
association between the event and 
study treatment 
 
Within the following 48 hours, the investigator must provide further information on the 
serious adverse event in the form of a written narrative.  This should include a copy of the 
completed Serious Adverse Event form, and any other diagnostic information that will 
assist the understanding of the event.  Significant new information on ongoing serious 
adverse events should be provided promptly to the study sponsor 
8.3.2 EC/IRB Notification by Investigator 
Reports of all serious adverse events (including follow-up information) must be submitted 
to the EC/IRB within 10 working days.  Copies of each report and documentation of 
EC/IRB notification and receipt will be kept in the Clinical Investigator’s binder. 
8.3.3 FDA Notification by Sponsor 
The study sponsor shall notify the FDA by telephone or by facsimile transmission of any 
unexpected fatal or life-threatening experience associated with the use of the drug as soon 
as possible but no later than 7 calendar days from the sponsor’s original receipt of the 
information. 
 

 
 
Page 13 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
If a previous adverse event that was not initially deemed reportable is later found to fit the 
criteria for reporting, the study sponsor will submit the adverse event in a written report to 
the FDA as soon as possible, but no later than 15 calendar days from the time the 
determination is made. 
8.4 Unblinding Procedures 
Physicians performing the study intervention will not be blinded to the drug or technique.  The 
study participants, outcome assessors/researchers, other anesthesia personnel, surgeons, 
physician assistants, and nurses will be blinded to the treatment arm.  Unblinding will occur at 
the conclusion of the study in order to facilitate group analysis. 
8.5 Stopping Rules  
Not applicable. 
8.6 Medical Monitoring 
It is the responsibility of the Principal Investigator 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 (see section 9 Auditing, Monitoring and Inspecting).  Medical monitoring will include a 
regular assessment of the number and type of serious adverse events. 
8.6.1 Internal Data and Safety Monitoring Board 
 
8.6.2 Independent Data and Safety Monitoring Board 
 
9 Data Handling and Record Keeping 
9.1 Confidentiality 
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act (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. 

 
 
Page 14 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
9.2 Source 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 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. 
9.3 Case Report Forms 
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. 
9.4 Records Retention 
For FDA-regulated studies the following sample language is appropriate: 
 
It is the investigator’s responsibility to retain study essential documents for at least 2 years after 
the last approval of a marketing application in their country and until there are no pending or 
contemplated marketing applications in their country or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product.  These documents 
should be retained for a longer period if required by an agreement with the sponsor.  In such an 
instance, it is the responsibility of the sponsor to inform the investigator/institution as to when 
these documents no longer need to be retained.  
 
10 Study Monitoring, Auditing, and Inspecting 
10.1 Study Monitoring Plan 
Not applicable. 
10.2 Auditing and Inspecting 
The investigator will permit study-related monitoring, audits, and inspections by the EC/IRB, 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.). 
 

 
 
Page 15 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
Participation as an investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable University compliance and quality assurance 
offices. 
11 Ethical Considerations 
This study is to be conducted according to US and international standards of Good Clinical 
Practice (FDA Title 21 part 312 and International Conference on Harmonization guidelines), 
applicable government regulations and Institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to a properly constituted independent 
Ethics Committee (EC) or Institutional Review Board (IRB), in agreement with local legal 
prescriptions, for formal approval of the study conduct.  The decision of the EC/IRB concerning 
the conduct of the study will be made in writing to the investigator and a copy of this decision 
will be provided to the sponsor before commencement of this study.  The investigator should 
provide a list of EC/IRB members and their affiliate to the sponsor. 
 
All subjects for this study will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in this 
study.  See Attachment D for a copy of the Subject Informed Consent Form.  This consent form 
will be submitted with the protocol for review and approval by the EC/IRB for the study.  The 
formal consent of a subject, using the EC/IRB-approved consent form, must be obtained before 
that subject is submitted to any study procedure.  This consent form must be signed by the 
subject or legally acceptable surrogate, and the investigator-designated research professional 
obtaining the consent.  
 
12 Study Finances 
12.1 Funding Source 
Internally funded 
12.2 Conflict 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 a properly constituted Conflict of Interest Committee with a Committee-
sanctioned conflict management plan that has been reviewed and approved by the study sponsor 
prior to participation in this study.  All University of Pennsylvania investigators will follow the 
University conflict of interest policy. 
12.3 Subject Stipends or Payments 
Not applicable. 
13 Publication Plan 
Neither the complete nor any part of the results of the study carried out under this protocol, nor 
any of the information provided by the sponsor for the purposes of performing the study, will be 

 
 
Page 16 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor 
published or passed on to any third party without the consent of the study sponsor.  Any 
investigator involved with this study is obligated to provide the sponsor with complete test 
results and all data derived from the study. 
14 References 
1. Memtsoudis SG et al.  “Inpatient falls after total knee arthroplasty: the role of anesthesia 
type and peripheral nerve blocks.”  Anesthesiology.  2014 Mar; 120(3):551-63. 
2. Gabriel RA et al.  “Utilization of femoral nerve blocks for total knee arthroplasty.”  J 
Arthroplasty.  2016 Aug; 31(8):1680-5. 
3. Gao F et al.  “Adductor canal block versus femoral nerve block for analgesia after total 
knee arthroplasty: a systematic review and meta-analysis.”  Clin J Pain.  2016 Jun 17; 
epub. 
4. Jiang et al.  “Analgesic efficacy of adductor canal block in total knee arthroplasty: a 
meta-analysis and systematic review.”  Orthop Surg.  2016 Aug; 8(3):294-300. 
5. Patterson ME et al.  “The adductor canal block provides effective analgesia similar to a 
femoral nerve block in patients undergoing total knee arthroplasty – a retrospective 
study.”  J Clin Anesth.  2015 Feb; 27(1):39-44. 
6. Nercessian OA et al.  “Peroneal nerve palsy after total knee arthroplasty.”  J 
Arthroplasty.  2005; 20(8):1068-73. 
7. Thobhani A et al.  “Novel regional techniques in total knee arthroplasty promote 
reduced length of stay: an analysis of 106 patients.”  Submitted and under review for 
publication. 
15 Attachments 
A: random.org simulation 
B: Brief Pain Inventory 
C: Study Drug Package Inserts 
D: Subject Informed Consent Form 
 
 
 
 
 
 
 
 
 
 
 
ATTACHMENT A 

 
 
Page 17 
CONFIDENTIAL 
This material is the property of Ochsner Clinic Foundation.  Do not disclose or use except as authorized in writing by the study sponsor