Comparison Between Ipack Block and Periarticular Infiltration in Total Knee Arthroplasty - a Randomized Control Trial
Phase: PHASE4
Conditions: Osteo Arthritis Knee
Sponsor: Icahn School of Medicine at Mount Sinai

Comparison Between Ipack Block And Periarticular Infiltration In Total Knee Arthroplasty - A 
Randomised Controlled Trial 
PI: Dr. Yan Lai 
NCT03653416 
Document Date: July 22, 2017

 
Protocol Name: 
COMPARISON BETWEEN IPACK BLOCK AND 
PERIARTICULAR INFILTRATION IN TOTAL KNEE 
ARTHROPLASTY - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD. 
 
Date Revised: 
7/22/2017 
Study Number: 
 IF# 2087568 , GCO#17-04304 
 
1 
Revised 9/2/14 
HRP-503 PROTOCOL TEMPLATE  
• 
Note that, depending on the nature of your research, certain questions, directions, or entire sections below 
may not be applicable. Provide information if and when applicable, and in cases where an entire section is not 
applicable, indicate this by marking the section “N/A”.  Do not delete any sections. 
• 
For any items below that are already described in the sponsor’s protocol, the investigator’s protocol,  the 
grant application, or other source documents, you may simply reference the title and page numbers of these 
documents in the sections below, rather than cutting and pasting into this document. Do not refer to the 
Sample Consent document, or information on the application form in this document.. 
• 
Keep an electronic copy of this version of the document. You will need to modify this copy when making 
changes. 
 
Brief Summary of Research (250-400 words):  
Total knee arthroplasty (TKA) is an effective modality for the treatment of advanced 
osteoarthritis of the knee joint with excellent outcomes. With 719,000 cases being 
performed as of 2010, the incidence is expected to increase up to 3.48 million 
procedures annually by 2030.  Multimodal analgesia is the cornerstone intervention 
in TKA that is utilized to minimize postoperative pain and improve functional 
outcomes in patients. Pain management in perioperative period enhances recovery 
and rehabilitation that improves length of stay and facilitates faster discharge with 
improvements in patient satisfaction scores.  Numerous strategies devised as a part 
of multimodal analgesia after TKA are epidural anesthesia, femoral nerve block, 
adductor canal block, intra articular epidural catheter (Caledonian protocol), intra 
articular cocktail, intra venous patient control analgesia along with IV analgesics 
and combinations. The goal to minimize narcotics has been based on several studies 
demonstrating opioid related adverse events, increased length of stay as well as 
hospitalization costs. 
 
Local infiltrative analgesia administered by the surgeon around the joint capsule has 
been an emerging adjunct to multimodal analgesia advocated by surgeons claiming 
improved rehabilitation by reducing venous stasis and maximizing motor strength. 
Periarticular analgesia (PAI) primarily targets the mechanoreceptors and the free 
nerve endings in the intra articular area.  
 

 
Protocol Name: 
COMPARISON BETWEEN IPACK BLOCK AND 
PERIARTICULAR INFILTRATION IN TOTAL KNEE 
ARTHROPLASTY - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD. 
 
Date Revised: 
7/22/2017 
Study Number: 
 IF# 2087568 , GCO#17-04304 
 
2 
Revised 9/2/14 
IPACK block is a novel technique gaining popularity where one injects local 
anesthesia safely under ultrasound guidance in the interspace between the popliteal 
artery and capsule of the knee. It primarily targets genicular nerves innervating the 
knee joint. It does not affect the sciatic nerve hence motor blockade is avoided 
promising enhanced recovery.  
 
There have been no studies till date comparing the efficacy between IPACK block 
and PAI. 
 
The purpose of our study is to evaluate the difference in quality of analgesia 
between efficacy of IPACK block and PAI performed by surgeon as measured by 
patient’s opioid consumption and pain scores.  
 
 
1)Objectives 
Research Question: Does IPACK block provide superior analgesia in comparison 
with surgeon performed periarticular infiltrate (PAI) in TKA patients? 
 Primary outcome: The amount of opioid consumption (in mg IV morphine 
equivalents) postoperatively during the first 24 hours after the procedure. VAS pain 
scores on arrival and departure from PACU. 
Secondary outcome: 
The degree of postoperative pain in terms of VAS scores from arrival to the floors to 
the first 24 hours after surgery. 
Time to first dose of narcotic administration, PACU length of stay, location of pain,              
ambulation distance with assistance on POD 1 as assessed by PT and activities of 
daily living(ADL’s) on POD 1 as assessed by OT.  
 
2)Background 
See above. There have been several studies regarding efficacy of peri-articular 
infiltration. IPACK block is a novel technique gaining popularity where one injects 

 
Protocol Name: 
COMPARISON BETWEEN IPACK BLOCK AND 
PERIARTICULAR INFILTRATION IN TOTAL KNEE 
ARTHROPLASTY - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD. 
 
Date Revised: 
7/22/2017 
Study Number: 
 IF# 2087568 , GCO#17-04304 
 
3 
Revised 9/2/14 
local anesthesia safely under ultrasound guidance in the interspace between the 
popliteal artery and capsule of the knee.  
There have been no studies till date comparing the efficacy between IPACK block 
and PAI. 
 
3)Setting of the Human Research 
Prospective triple blinded randomized control trial undergoing total knee 
arthroplasty surgeries. The research study will take place at Mount Sinai West 
hospital and Mount Sinai St. Luke’s hospitals. The site PI is Yan Lai, MD, MPH. 
 
4)Resources Available to Conduct the Human Research 
For n=200, the feasibility of recruitment is manageable. Recruitment will be done 
through a coordination of the operating schedule and the surgeon’s office.  Patients 
presenting for preoperative visits at the preoperative joint clinic will be approached. 
Patients routinely are seen by anesthesiologists at the pre operative testing clinic as 
part of pre operative anesthetic evaluation. Patients will be approached by research 
personnel and details of the study will be explained. The consent will be obtained in 
the pre operative testing clinic after all questions are thoroughly answered. After 
confirmation on the operating schedule, patients will be provided detailed 
instructions the day before surgery. The staff members on this protocol are all 
employees of Mount Sinai and will either be a resident or attending physicians that 
are included on the IRB protocol. There are two primary members of the research 
personnel: 
     a)Yan Lai, MD, MPH – Roles for Dr. Lai in this study include serving as primary 
investigator      responsible for study design and planning, data collection, subject 
recruitment, manuscript writing and preparation, data analysis, safety monitoring, 
and responding to adverse events and/or complications. He is certified in PPHS/IRB 
protocols, all Citi/IRB required training in human subject protection, and has prior 
clinical research experience. He is also a board certified anesthesiologist and 
assistant professor of anesthesiology with the Icahn School of Medicine and the 
Mount Sinai Health System. 

 
Protocol Name: 
COMPARISON BETWEEN IPACK BLOCK AND 
PERIARTICULAR INFILTRATION IN TOTAL KNEE 
ARTHROPLASTY - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD. 
 
Date Revised: 
7/22/2017 
Study Number: 
 IF# 2087568 , GCO#17-04304 
 
4 
Revised 9/2/14 
     b) Poonam Pai. B.H MD – Roles for Dr. Pai include serving as primary research 
coordinator involved in data collection, subject recruitment, manuscript writing and 
preparation, data analysis, safety monitoring, and responding to adverse events 
and/or complications.  She has completed all of her required CITI training to be IRB 
certified and has experience in clinical research. In addition she has been a resident 
physician in anesthesiology with the Icahn School of Medicine in good standing for 
the previous three years going on her fourth. 
There are institutional processes to ensure that all persons assisting with the protocol 
will be well informed.  The research personnel will conduct regular meetings and 
department email updates to review the results and safety data of the study.  The 
research personnel will initiate the formation of a safety monitoring board for 
adverse effects, complications, or complaints from patient subjects. 
 
 
 5) Study Design 
Prospective triple blinded randomized control trial. Recruitment will be done 
through a coordination of the operating schedule and the surgeon’s office.  Patients 
presenting for preoperative visits at the preoperative joint clinic will be approached. 
Patients routinely are seen by anesthesiologists at the pre operative testing clinic as 
part of pre operative anesthetic evaluation. Patients who meet the inclusion criteria 
will be approached by research personnel and details of the study will be explained. 
The consent will be obtained in the pre operative testing clinic after all questions are 
thoroughly answered. The team will finalize participation and ask the subject to sign 
study consent forms.  All patients will be provided with copies of the IRB protocol 
and consent if they wish to have it. Copy of the consent form will be sent in a 
secured email to the potential subject. The email will be secured by entering in 
[SECURE] in the e-mail subject line.  Once recruited blinding assessments will be 
done by the study team.  
Patients will be assigned randomly using a computer- generated table of numbers to 
either IPACK block (IPACK group) or Periarticular infiltration (PAI group). Block 
team will perform all blocks. Resident anesthesiologist will know the group 
allocation but will not be involved in the study. Patients assigned to IPACK block 
group will receive 20cc 0.25% bupivacaine under USG guidance on the side of 

 
Protocol Name: 
COMPARISON BETWEEN IPACK BLOCK AND 
PERIARTICULAR INFILTRATION IN TOTAL KNEE 
ARTHROPLASTY - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD. 
 
Date Revised: 
7/22/2017 
Study Number: 
 IF# 2087568 , GCO#17-04304 
 
5 
Revised 9/2/14 
surgery. At the conclusion of the surgery prior to skin closure, all patients in the PAI 
group will receive 100cc of joint cocktail infiltrated by the surgeon. Patients in both 
groups will receive a post operative adductor canal catheter in the PACU, with 
Bupivacaine 0.1% 8-12 cc/hr with demand dose of 3-5 cc q20 min.  Otherwise, the 
patient, surgeon, and anesthesiologist in the case will be blinded.   
 
a) Recruitment methods: Patients will be recruited and consented in pre operative 
testing/Joint clinic. 
b) Inclusion and Exclusion Criteria 
   Inclusion criteria: ASA (American Society of Anesthesiology) class I-IV, age 18-     
75. 
Exclusion criteria: ASA class V, morbid obesity, patient refusal, patients with 
chronic pain or on pain medications, allergy to LA, patients receiving any additional 
regional techniques, coagulopathy, patients receiving systemic anticoagulation, local 
infection, and procedures anticipated to last more than 5 hours.  
     c)Number of Subjects 
We intend to recruit 200 patients. 
Based on a confidence level of 99% with a Z score of 2.58, standard deviation of .5 
and a confidence interval of 10% our sample size should be 166. For ease of 
statistical calculations we rounded up to 200 patients. Based on previous literature 
pertaining to local articular infiltration in total knee arthroplasty and postoperative 
femoral nerve block, we found studies included anywhere from 40 to 100 patients. 
We intend to use a higher sample size to see any statistical significance. 
 
ss = 
Z 2 * (p) * (1-p) 
c 2 
 
Where: 

 
Protocol Name: 
COMPARISON BETWEEN IPACK BLOCK AND 
PERIARTICULAR INFILTRATION IN TOTAL KNEE 
ARTHROPLASTY - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD. 
 
Date Revised: 
7/22/2017 
Study Number: 
 IF# 2087568 , GCO#17-04304 
 
6 
Revised 9/2/14 
Z 
= 
Z 
value 
(2.58 
for 
99% 
confidence 
level)  
p = percentage picking a choice, expressed as decimal (.5 used for sample size needed) 
c = confidence interval, expressed as decimal  (e.g., .01= ±1) 
 
Sample size= [(2.58^2)(.5)(.5)]/(.1^2)=166 subjects 
For effect size, we expect a Cos d medium effect of 0.5. The estimate for sample 
sizes was obtained by using the first set of pain scores obtained in the PACU. A 
previous study of 45 patients undergoing knee arthroplasty treated with a femoral 
nerve block reported a mean visual analog scale score of 3.6 (SD 1.1) upon 
movement, at 24 h (Singelyn et al. 1998). In an earlier study on total knee 
arthroplasties (Axelsson et al. 2005), the mean morphine consumption over 48 hours 
postoperatively was 64.6 (SD 36.3) mg in the placebo group.  
 
The aim of this study was to investigate whether the IPACK technique could reduce 
the morphine consumption.  The Mann-Whitney U test will be used for the analysis 
of the primary endpoint (morphine consumption). Mann-Whitney U test will be used 
to assess pain scores and the Bonferroni-Holm method was used to correct for 
multiple measures. Hospital stay, time to fulfill discharge criteria, knee function 
scores, and patient satisfaction scores will be analyzed using the Mann-Whitney U 
test. Dichotomous data will be analyzed using the chi-squared test or Fisher's exact 
test, as appropriate. Values of p < 0.05 were considered to be statistically 
significant. 
 
 
d)Study Timelines 
     2017-2018 and subsequent data analysis. The subject’s participation will be from 
time of enrollment in the pre-operative period until first 24 hours after surgery. 
Estimated date of enrollment completion will be when 200 eligible subjects are 
enrolled in final data analysis.  Estimate date for study completion will be June 
2018. 
 
 

 
Protocol Name: 
COMPARISON BETWEEN IPACK BLOCK AND 
PERIARTICULAR INFILTRATION IN TOTAL KNEE 
ARTHROPLASTY - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD. 
 
Date Revised: 
7/22/2017 
Study Number: 
 IF# 2087568 , GCO#17-04304 
 
7 
Revised 9/2/14 
e)Endpoints 
The primary endpoints will be the amount of opioid consumption (in mg IV 
morphine equivalents) postoperatively up to 24 hours after the surgery. 
 
f)Procedures Involved in the Human Research 
Prospective randomized controlled trial and data analysis only. IPACK block and 
PAI. Intraoperative care of the patient will be provided by an anesthesia team 
member who is a part of the Mount Sinai System. The anesthesia provider will not 
be aware of the randomization of the patient.  Standard post-operative orders will be 
written for patients during their time in the PACU. 
 
g)Specimen Banking 
 N/A  
 
h)Data Management and Confidentiality 
Data collected in excel file to be de-identified after initial collection. Excel file be 
subsequently encrypted and shared only between the above listed investigators via 
secure Mt. Sinai (chpnet) electronic mail.  The information included in the data will 
be medical record number, age, gender, ASA class, type of surgery, pain score 
assessments, and time to first narcotic, total narcotic use and satisfaction/pain scores 
during the first 24 hours after surgery. Pain scores on arrival and discharge from 
PACU, PACU length of stay, location of pain, and ambulation distance with 
assistance on POD 1 as assessed by PT and activities of daily living (ADL’s) on 
POD 1 as assessed by OT will be other data collected. 
Only the research personnel will have access to the data. The data will be stored as a 
hard copy files and on a secure spreadsheet. The research personnel is responsible 
for the receipt of the data. The PI will keep the hard copies secure and any electronic 
data will be encrypted. No personal identifiers will be used. The data will undergo 
statistical analysis 
 
 
 

 
Protocol Name: 
COMPARISON BETWEEN IPACK BLOCK AND 
PERIARTICULAR INFILTRATION IN TOTAL KNEE 
ARTHROPLASTY - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD. 
 
Date Revised: 
7/22/2017 
Study Number: 
 IF# 2087568 , GCO#17-04304 
 
8 
Revised 9/2/14 
i)Provisions to Monitor the Data to Ensure the Safety of Subjects 
       Part I: Elements of Data and Safety Monitoring Plan 
MSSM Principal Monitor: 
 
Last Name: Lai 
First Name: Yan 
Academic Title: Attending Physician, Assistant Professor 
Department: Anesthesiology 
Mailing Address: Mount Sinai West 1000 10th Avenue, New York, NY 10019 
Phone: 212-523-6915 
Fax:  
E-mail: ylai@chpnet.org 
 
 
MSSM Additional Monitor: 
 
Last Name: Pai B.H 
First Name: Poonam 
Academic Title: Research Personnel, Physician 
Department: Anesthesiology 
Mailing Address: Mount Sinai West 1000 10th Avenue, New York, NY 10019 
Phone: 212-523-6915 
Fax:  
E-mail: phebbalasankatte@chpnet.org 
 
The principal monitor is a board certified anesthesiologist thus minimizing the risk 
to the subjects and further optimizing their health and wellbeing. Adverse events 
will be monitored as a standard of care everyone receives regardless of participation 
in the study. The safety and data information will be reviewed on a daily basis until 
the desired sample size is achieved. All temporary and/or permanent suspensions 
will be reported.  
Poonam Pai B.H MD – Roles for Dr. Pai include serving as primary research 
coordinator involved in data collection, subject recruitment, manuscript writing and 
preparation, data analysis, safety monitoring, and responding to adverse events 
and/or complications.  She has completed all of her required CITI training to be IRB 
certified and has experience in clinical research. In addition she has been a resident 
physician in anesthesiology with the Icahn School of Medicine in good standing for 
the previous three years going on her fourth. 

 
Protocol Name: 
COMPARISON BETWEEN IPACK BLOCK AND 
PERIARTICULAR INFILTRATION IN TOTAL KNEE 
ARTHROPLASTY - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD. 
 
Date Revised: 
7/22/2017 
Study Number: 
 IF# 2087568 , GCO#17-04304 
 
9 
Revised 9/2/14 
 
j)Withdrawal of Subjects 
 Patients may withdraw from the study at any given time by contacting any member 
of the research study group. Data will not be collected on patients who wish to 
withdraw. Patient do not need to withdraw consent in writing. 
 
6)Risks to Subjects 
If patients are injured or made sick from taking part in this research study, medical care 
will be provided. Generally, this care will be billed to the patient or their insurance in the 
ordinary manner and the patient will be responsible for all treatment costs not covered 
insurance, including deductibles, co-payments and coinsurance.  This does not prevent the 
patient from seeking payment for injury related to malpractice or negligence. Contact the 
investigator for more information. 
 
As with any medication, there is a possibility of an allergic reaction. Although rare, 
possible complications include LA toxicity, hypersensitivity reaction, bleeding or 
local site infection, chance of pneumothorax. All anesthesiologists involved in 
patient care will be prepared for the prevention and rescue for any complications 
involving local anesthetic injections. 
 
7)Provisions for Research Related Harm/Injury 
If patients are injured or made sick from taking part in this research study, medical care 
will be provided. Generally, this care will be billed to the patient or their insurance in the 
ordinary manner and the patient will be responsible for all treatment costs not covered 
insurance, including deductibles, co-payments and coinsurance.  This does not prevent the 
patient from seeking payment for injury related to malpractice or negligence. Contact the 
investigator for more information. 
 
8)Potential Benefits to Subjects 
It is important to know that you may not get any benefit from taking part in this 
research.  Others may not benefit either. However, possible benefits may be 
improved knowledge about how the different forms of analgesia affect pain control 
in knee surgery. There is potential for better pain control after the surgery. 

 
Protocol Name: 
COMPARISON BETWEEN IPACK BLOCK AND 
PERIARTICULAR INFILTRATION IN TOTAL KNEE 
ARTHROPLASTY - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD. 
 
Date Revised: 
7/22/2017 
Study Number: 
 IF# 2087568 , GCO#17-04304 
 
10 
Revised 9/2/14 
 
9)Provisions to Protect the Privacy Interests of Subjects 
Patients will be appropriately educated about the research study. Any questions or 
concerns they have will be adequately addressed and patients will have the option to 
decline participation. Patients will be given as much time as they need to review the 
consent form. The study personnel will be approaching the subjects. Privacy will be 
maintained by not including any identifiers such as names or addresses in the data 
collected.  
The identities of human subjects whose data is being studied will be de-identified as 
per HIPAA Privacy Rule. 
 
10)Economic Impact on Subjects 
Patients will not incur any additional cost for participating in the study. The 
medications used are part of a standard anesthetic regimen that will be billed to 
subject’s insurance as bundled standard of anesthesia care. The cost of the procedure 
is overall unaffected.   
 
11)Payments to Subjects 
 Patients will not be reimbursed for their participation. 
 
12)Consent Process 
Informed consent will be obtained prior to the procedure. Both the HRP-090 (SOP) 
Informed Consent Process for Research and the HRP-091 (SOP) Written 
Documentation of Consent will be followed by the study team. These documents are 
both 
available 
at 
http://icahn.mssm.edu/research/resources/program-for-
the-protection-of-human-subjects/irb-members-palette. 
 
 
 
 
 

 
Protocol Name: 
COMPARISON BETWEEN IPACK BLOCK AND 
PERIARTICULAR INFILTRATION IN TOTAL KNEE 
ARTHROPLASTY - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD. 
 
Date Revised: 
7/22/2017 
Study Number: 
 IF# 2087568 , GCO#17-04304 
 
11 
Revised 9/2/14 
13.Process to Document Consent in Writing 
The patients will receive a paper copy of the IRB approved consent packet and will 
sign in the designated areas to confirm consent of participation.  They will have the 
option of have a copy of the consent and may ask for a personal copy of the consent.  
 
 
14.Vulnerable Populations 
Indicate specifically whether you will include (target) or exclude each of the following 
populations: 
I
n
c
l
u
d
e 
E
x
c
l
u
d
e 
Vulnerable Population Type 
 
X 
Adults unable to consent 
 
X 
Individuals who are not yet adults (e.g. infants, children, teenagers) 
 
X 
Wards of the State (e.g. foster children) 
 
X 
Pregnant women 
 
X 
Prisoners 
 
15.Multi-Site Human Research (Coordinating Center) 
 
This study will be performed within the Mount Sinai West and St. Luke’s Hospitals. 
No additional centers will be involved. 
 
 
 

 
Protocol Name: 
COMPARISON BETWEEN IPACK BLOCK AND 
PERIARTICULAR INFILTRATION IN TOTAL KNEE 
ARTHROPLASTY - A RANDOMISED CONTROLLED TRIAL 
Principal Investigator:  
YAN LAI MD,MPH. 
Primary Contact 
Name/Contact Info: 
POONAM PAI B.H MD. 
 
Date Revised: 
7/22/2017 
Study Number: 
 IF# 2087568 , GCO#17-04304 
 
12 
Revised 9/2/14 
16.Community-Based Participatory Research 
 
This does not apply to our study. 
 
17.Sharing of Results with Subjects 
Results will not be shared with the patients since the study will take time to 
complete.  Patients can request results if they contact the PI by writing. 
 
18.External IRB Review History 
This does not apply to our study. 
 
19.Control of Drugs, Biologics, or Device  
Not applicable.  Local anesthetic are routinely used in this setting.