How Many Opiates Should we Prescribe for Pain in Patients Undergoing Knee Arthroscopies and ACL Reconstructions?
Phase: NA
Conditions: Knee Injuries, ACL Injury
Sponsor: Northwestern University

PROTOCOL TITLE: Knee arthroscopy and ACL reconstruction RCT study 
 
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Official title: How Many Opiates Should we Prescribe for Pain in Patients 
Undergoing Knee Arthroscopies and ACL Reconstructions?  
NCT number: NCT03876743   
Document date: 29Jan2020 
 
 

PROTOCOL TITLE: Knee arthroscopy and ACL reconstruction RCT study 
 
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PROTOCOL TITLE: 
How many opiates should we prescribe for pain in patients undergoing knee 
arthroscopies and ACL reconstructions? 
 
PRINCIPAL INVESTIGATOR: 
Vehniah Tjong, MD 
Northwestern University 
Department of Orthopaedic Surgery 
676 N. St. Clair, Suite 1350 
Chicago, IL 60611 
Vehniah.tjong@northwestern.edu 
 
 
VERSION NUMBER: 
4.0 
VERSION DATE: 
01/29/2020 
 

PROTOCOL TITLE: Knee arthroscopy and ACL reconstruction RCT study 
 
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Table of Contents 
1.0 
Objectives ................................................................................................................ 4 
2.0 
Background .............................................................................................................. 4 
3.0 
Inclusion and Exclusion Criteria .............................................................................. 4 
4.0 
Study-Wide Number of Subjects ............................................................................. 5 
5.0 
Study-Wide Recruitment Methods .......................................................................... 5 
6.0 
Multi-Site Research ................................................................................................. 5 
7.0 
Study Timelines ....................................................................................................... 5 
8.0 
Study Endpoints ....................................................................................................... 6 
9.0 
Procedures Involved................................................................................................. 6 
10.0 Data and Specimen Banking .................................................................................. 10 
11.0 Data and Specimen Management........................................................................... 10 
12.0 Provisions to Monitor the Data to Ensure the Safety of Subjects .......................... 11 
13.0 Withdrawal of Subjects* ........................................................................................ 11 
14.0 Risks to Subjects* .................................................................................................. 11 
15.0 Potential Benefits to Subjects ................................................................................ 11 
16.0 Vulnerable Populations .......................................................................................... 11 
17.0 Community-Based Participatory Research ............................................................ 11 
18.0 Sharing of Results with Subjects ........................................................................... 12 
19.0 Setting .................................................................................................................... 12 
20.0 Resources Available............................................................................................... 12 
21.0 Prior Approvals ...................................................................................................... 12 
22.0 Recruitment Methods ............................................................................................. 12 
23.0 Local Number of Subjects ..................................................................................... 12 
24.0 Confidentiality ....................................................................................................... 12 
25.0 Provisions to Protect the Privacy Interests of Subjects .......................................... 12 
26.0 Compensation for Research-Related Injury ........................................................... 13 
27.0 Economic Burden to Subjects ................................................................................ 13 
28.0 Consent Process ..................................................................................................... 13 
29.0 Process to Document Consent in Writing .............................................................. 13 
30.0 Drugs or Devices.................................................................................................... 14 
 

PROTOCOL TITLE: Knee arthroscopy and ACL reconstruction RCT study 
 
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1.0 
Objectives 
 The purpose of the study is to determine if opiates are required to 
achieve adequate analgesia after knee arthroscopy and ACL 
reconstruction in outpatient surgery. 
 We hypothesize that patients are frequently prescribed more 
opiates than are needed after surgery, resulting in excess 
medications that are at risk for misuse, diversion and contribution 
to the opioid epidemic. 
 
2.0 
Background 
Perioperative pain management is an important aspect of quality patient care. 
Opioid pain medications are increasingly being used for pain control, with the 
United States writing over 250 million prescriptions for painkillers per year[1]. 
Increased usage has led to unintended negative consequences for individuals and 
society. It is estimated that 46 people die each day from an overdose of 
prescription painkillers, and individual use can lead to the development of 
tolerance and worse treatment outcomes [1, 2]. Further issues arise when opioids 
are misused, it is estimated that nontherapeutic use has increased three fold in 
recent years[3]. In the United States alone in 2006 the estimated total cost of 
opioid prescription misuse was $53.4 billion, of which $42 billion was attributed 
to lost productivity, $8.2 billion to criminal justice cost and the remainder drug 
abuse treatment and medical complications[4]. The federal government has 
recognized this epidemic and raised a call for clinicians to more responsibly 
prescribe opiate pain medications[5]. 
 
Opiate use has increased in recent years, from 2000-2010 the use of opiates in 
office based visits nearly doubled from 11.3% to 19.6% whereas there was no 
change in the prescribing of non-opioid pharmacotherapies. Further, when 
specifically looking at new musculoskeletal pain visits, one half resulted in 
pharmacologic treatment, with the prescribing of non-opioid pharmacotherapies 
decreasing from 38%  to 29% from 2000 to 2010, respectively[6]. The clinical use 
of opioids for post-operative pain control has also been linked to the opioid 
epidemic and risk of future abuse[7]. Legitimate opioid use before high school 
graduation is independently associated with a 33% increased risk of future misuse 
after high school[8]. 
 
It has been estimated that orthopedic surgeons prescribe 7.7% of all opioids in the 
United States[9].Special attention needs to be paid to the amount of opioid pain 
medications orthopedic surgeons prescribe to patients after ambulatory surgery, 
there is considerable variability among surgeon and procedure in regards to the 
amount of opioids to prescribe with many patients left with excess unused 
medication[10].An analysis of 250 patients undergoing outpatient upper extremity 
surgery found that on average patients consumed 10 opioid pills, with 19 pills left 
over and a total of 4,639 pills going unused in the cohort[10]. Leftover 
prescription opioids are at risk for diversion to family and friends for nonmedical 
use[11]. Further studies are needed to quantify the amount of opioids to prescribe 

PROTOCOL TITLE: Knee arthroscopy and ACL reconstruction RCT study 
 
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for specific orthopedic procedures to limit excess narcotic use, misuse, diversion 
and contribution to the opioid epidemic. 
 
3.0 
Inclusion and Exclusion Criteria 
 Inclusion Criteria: 
o All patients presenting to Northwestern Memorial Hospital 
(NMH) or to a Northwestern orthopaedic surgery faculty 
member’s clinic undergoing knee arthroscopy with 
meniscus repair and/or debridement 
o 18 years old or greater 
o Ability to read and speak English 
 Exclusion Criteria: 
o Revision surgery 
o Oncologic surgery 
o Arthroscopic knee surgery that involves procedures other 
than ACL or the meniscus (i.e PCL, LCL, MPFL) 
o Patients currently taking narcotics, chronic pain 
management patients, history of substance abuse 
o Adults unable to consent 
o Individuals who are not yet adults (infants, children, 
teenagers) 
o Pregnant women 
o Prisoners 
o Patients currently taking narcotics, chronic pain 
management patients, history of substance abuse 
 
4.0 
Study-Wide Number of Subjects 
N/A 
 
5.0 
Study-Wide Recruitment Methods 
N/A 
 
6.0 
Multi-Site Research 
NA 
 
7.0 
Study Timelines 
This study will be observational in nature. Patient will fill out a 
preoperative questionnaire related to specific risk factors for opiate 
use/abuse. Following their operation a phone call will be placed at 24 
hours, 48 hours, and between 7-14 days after surgery and asked how many 
opiate pain medications they took, how many are left over and when the 
date they stopped taking them. If they are still taking pain medications at 
that point 1 follow-up call will be placed at 21 days again asking the same 
questions. Maximum total length of the study will be 21 days post-
surgery. 

PROTOCOL TITLE: Knee arthroscopy and ACL reconstruction RCT study 
 
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8.0 
Study Endpoints 
This study is observational in nature. The study will end once we have collected 
data for 60 patients for each arm in order to sufficiently power the subsequent 
analysis as a level 1 prospective study. 
 
9.0 
Procedures Involved 
This study will be a pilot randomized control trial to establish non-
inferiority in opiate prescribing patterns.  
 
Eligible patients will be identified in clinic by the treating attending 
physician. Patients will subsequently be approached by research personnel 
at that time. In the event that a patient determines that they wish to pursue 
surgery and this is discussed by phone without an additional clinic visit 
they will be approached on the day of surgery by our research staff. 
 
All patients will fill out a preoperative questionnaire asking them the 
questions below related to specific risk factors for opiate use/abuse.  
 
 Age 
 Sex 
 BMI 
 Do you actively smoke cigarettes? 
 If no, have you ever consistently smoked cigarettes (daily for > 1 month)? 
 What is your employment status? 
 Is this injury part of a workers’ compensation claim? 
 Are you actively participating in organized sporting activities? If so, at 
what level (i.e. professional, college, recreational)? 
 Are you currently using narcotic pain medications? 
 Do you have a personal history of substance abuse (ex. prescription or 
illicit drugs, alcohol)? 
 Do you have a family history of substance abuse (ex. prescription or illicit 
drugs, alcohol)? 
 What is the highest level of education you attained? 
 What is your average yearly household income? 
 
Additionally, the patients undergoing knee arthroscopy will be 
randomized into two groups prior to surgery by the research staff. The 
surgeons’ physician assistants will be responsible for prescribing the 
appropriate medications. 
 
 Group 1: Will have all of their post-operative prescriptions sent 
down to the pharmacy on the day of surgery to be collected. 
 Group 2: Will have all prescriptions sent to pharmacy with the 
exception of an opiate prescription. Instead, they will be handed a 

PROTOCOL TITLE: Knee arthroscopy and ACL reconstruction RCT study 
 
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physical paper prescription. They will be instructed to only fill the 
prescription if absolutely needed.  
 
The patients undergoing ACL reconstruction surgery will be randomized 
into two groups prior to surgery by the research staff. The surgeons’ 
physician assistants will be responsible for prescribing the appropriate 
medications. 
 Group 1: Will be prescribed 60 opiate tablets in addition to other 
routine post-operative pain medication regimens.  
 Group 2: Will be prescribed 30 opiate tablets in addition to other 
routine post-operative pain medication regimens. 
 
In order to limit potential variability in sample size, block randomization 
will be utilized with the following parameters: 18 blocks with 5 patients in 
each block. The blocks will be as follows (Block #/#/#): 
 
Block (1/7/13) 
22112 
 
Block (2/8/14) 
11221 
 
Block (3/9/15) 
21121 
 
Block (4/10/16) 
21122 
 
Block (5/11/17) 
21211 
 
Block (6/12/18) 
22121 
 
A computer program will randomly select a block number. Once a block is 
selected patients will be enrolled in the order listed in the block. For 
example, if block 6 is selected initially Patient 1 will be enrolled in Group 
2, Patient 2 will be enrolled in group 2, Patient 3 will be enrolled in group 
1, etc. After every 5th patient is randomized to a group a new block will be 
randomly selected.  
 
The surgeons’ physician assistants will be responsible for prescribing the 
appropriate medications. To clarify, we do not electronically prescribe C2 
medications as a routine part of practice and do not intend to as part of the 
study. 
 

PROTOCOL TITLE: Knee arthroscopy and ACL reconstruction RCT study 
 
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All patients will be provided the same counseling regardless of the amount 
of narcotics they are prescribed. In the event that a patient requires 
additional narcotics on top of the original prescription the treating surgeon 
will need to be notified in order to accurately assess the amount already 
consumed and appropriately prescribe additional medications. 
 
Please note that there is considerable variability in opiate prescribing 
between practitioners. Patient's that undergo ACL reconstruction typically 
are prescribed between 30-60 Norco depending on the practitioner. Our 
randomization falls within the variability of the current standard for which 
there is no evidence based literature. Additionally, we are attempting to 
discern if 30 opiate tablets would be sufficient for patients undergoing 
ACL reconstruction. We suspect that the majority of patients prescribed 
60 tablets do not take greater than 50% of what they are prescribed. We 
are interested in determining the number of opiates left over after ACL 
reconstruction and if the amount prescribed affects the total amount 
consumed. 
 
Following their operation, all patients will have Pain -Numeric Pain 
Rating Scale (NPRS) assessed at 2 hours post-surgery by the authorized 
co-investigators or research staff while the patient is recovering in the 
post-anesthesia care unit (PACU).  
 
Additionally, a phone call will be placed at 24 hours, 48 hours and 
between 7-14 days after surgery and asked a Numeric Pain Rating Score 
(NPRS), how many opiate pain medications they took, how many are left 
over and when the date they stopped taking them.  
NPRS scores can be performed verbally. The following statement will be 
provided to patients:  
The 11-point numeric scale ranges from '0' representing one pain extreme 
(e.g. “no pain”) to '10' representing the other pain extreme (e.g. “pain as 
bad as you can imagine” or “worst pain imaginable”), please rate your 
pain on a scale of 0-10. 
If they are still taking pain medications at that point, an additional follow-
up call will be placed at 21 days (+1-3 days) after surgery asking the same 
questions. We will allow 4 total phone calls (24 hours, 48 hours, 7-14 
days, and 21 (+ 1 to 3) days post-surgery. If patients continue to take 
narcotics 21 days after surgery they will be listed as >3 weeks of narcotic 
use) 
 
Refill requests will also be recorded.  
 
Maximum total length of the study will be 21 days post-surgery. 
 

PROTOCOL TITLE: Knee arthroscopy and ACL reconstruction RCT study 
 
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Knee Arthroscopy 
 
All Patients: Preoperative Questionnaire 
Randomization – Two Groups 
Group 1, n=60 
Group 2, n=60 
 Post-Operative 
Medication Regimen: 
o All scripts sent to 
pharmacy 
- 
Aspirin 325mg 
BID x7 days (14 
tabs) 
- 
Naproxen 500mg 
BID x7 days (14 
tabs) 
- 
Tylenol 1000mg 
BID x7 days (14 
tabs) 
- 
Oxycodone 20mg 
q6 PRN (20 tabs) 
 Post-Operative 
Medication Regimen: 
o All scripts EXCEPT 
Oxycodone sent to 
pharmacy 
- 
Aspirin 325mg BID 
x7 days (14 tabs) 
- 
Naproxen 500mg 
BID x7 days (14 
tabs) 
- 
Tylenol 1000mg 
BID x7 days (14 
tabs) 
- 
Oxycodone 20mg 
q6 PRN 20 tab 
prescription 
Postoperative Follow-Up 
2 hours – NPRS Pain Scores 
24 hours – NPRS Pain Scores, Opiate Count, Side Effects, Still 
Taking?, Refill Requests 
48 hours – NPRS Pain Scores, Opiate Count, Side Effects, Still 
Taking?, Refill Requests  
7 -14 days – NPRS Pain Scores, Opiate Count, Side Effects, Still 
Taking?, Refill Requests 
 
 
ACL Reconstruction 
 
All Patients: Preoperative Questionnaire 
Randomization – Two Groups 
Group 1, n=60 
Group 2, n=60 
 Post-Operative 
Medication Regimen: 
o All scripts sent to 
pharmacy 
- 
Aspirin 325mg BID 
x7 days (14 tabs) 
 Post-Operative 
Medication Regimen:  
o All scripts sent to 
pharmacy 
- 
Aspirin 325mg BID 
x7 days (14 tabs) 

PROTOCOL TITLE: Knee arthroscopy and ACL reconstruction RCT study 
 
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- 
Naproxen 500mg 
BID x7 days (14 
tabs) 
- 
Norco 10-325, 1-2 
tabs q6 PRN (60 
tabs) 
- 
Naproxen 500mg BID 
x7 days (14 tabs) 
- 
Norco 10-325, 1-2 
tabs q6 PRN (30 tabs) 
Postoperative Follow-Up – All Patients 
2 hours – NPRS Pain Scores 
24 hours – NPRS Pain Scores, Opiate Count, Side Effects, Still 
Taking?, Refill Requests 
48 hours – NPRS Pain Scores, Opiate Count, Side Effects, Still 
Taking?, Refill Requests  
7 -14 days – NPRS Pain Scores, Opiate Count, Side Effects, Still 
Taking?, Refill Requests 
 
The following data will also be retrieved from each study subject’s EMR through the 
NMEDW: 
 
 Intra-operative reports 
 Results of clinical examinations 
 Medical history (i.e. comorbid conditions, historical/current medications, surgical 
history) 
 Perioperative data (pain scores before and after surgery, drugs given, anesthesia 
blocks) 
 
 
10.0 Data and Specimen Banking 
Identifiable data will be collected and transcribed into NU SharePoint in Excel 
format. All survey data will be collected through REDCap. Access to both these 
databased will only be available to members of Dr. Tjong’s research team.  
Identifying information will be kept separately.  Subjects’ privacy interest will be 
maintained as they will only interact with or provide sensitive information to 
members of Dr. Tjong’s research team after they have confirmed interest in 
enrolling in the study.   
 
Research data will be stored electronically, password-protected, and encrypted on 
NU SharePoint and REDCap.  Only members of the research team will have 
access to the data.  Recorded data will be retained for a period of 5 years 
following completion of the study per NU policy on data retention for Human 
Subjects research. All data will thereafter be permanently deleted. 
 
11.0 Data and Specimen Management 

PROTOCOL TITLE: Knee arthroscopy and ACL reconstruction RCT study 
 
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The above data will be collected for each patient. Mean opiate use and left 
over opiates will be reported. Demographic data will be recorded, linear 
regression will be performed to determine risk for prolonged opiate use.  
 
Study is observational with reporting of means as the main outcome 
measure, no power analysis is necessary. 
 
Each member of Dr. Tjong’s research team has been CITI-certified for 
human subjects’ research.  Only members of Dr. Tjong’s research team 
will have access to study data, which will be encrypted on a secure server 
with separations of identifiers and subject data.   
 
Research data will be stored electronically, password-protected, and 
encrypted on a Northwestern Medicine secure server.  Only members of 
the research team will have access to the data.  Recorded data will be 
deleted at study completion and transcripts stored in a locked file drawer 
at Northwestern Memorial Hospital for future studies.   
 
 
12.0 Provisions to Monitor the Data to Ensure the Safety of Subjects 
N/A 
 
13.0 Withdrawal of Subjects* 
N/A 
 
14.0 Risks to Subjects* 
No identifiable physical risks to the patient are foreseen. Some of the 
preoperative questionnaire questions may be upsetting to patients. 
Specifically questions about personal or family history of substance abuse. 
 
There are no procedures included in this study that have risks that are currently 
unknown. Our planned opiate prescription amounts fall within the normal 
variability of current practice at Northwestern.  
 
There are no risks to others who are not subjects of the study. 
 
15.0 Potential Benefits to Subjects 
N/A 
 
16.0 Vulnerable Populations 
N/A 
 
17.0 Community-Based Participatory Research 
N/A 
 

PROTOCOL TITLE: Knee arthroscopy and ACL reconstruction RCT study 
 
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18.0 Sharing of Results with Subjects 
N/A 
 
19.0 Setting 
Northwestern Memorial Hospital (NMH) or to a Northwestern orthopedic 
surgery faculty member’s clinic. 
 
20.0 Resources Available 
Our Northwestern faculty are board certified orthopedic surgeons and 
foremost experts in their respective fields. The study is observational in 
nature.  
 
Drs. Tjong, Terry, and Gryzlo combined perform approximately 250 knee 
arthroscopy procedures per year. We anticipate at least 80% will enroll in 
the study and data will be able to be collected within 3-6 months. There 
are no anticipated medical risks to this study, should any psychological 
issues arise patients will be referred to Northwestern faculty in the 
psychiatry department. All persons involved in the research will be CITI 
certified, they will be briefed on the protocol, their duties and functions to 
ensure absolute understanding of our study. 
 
21.0 Prior Approvals 
N/A 
 
22.0 Recruitment Methods 
Eligible patients will be identified in clinic by the treating attending 
physician. Patients will subsequently be approached by research personnel 
at that time. In the event that a patient determines that they wish to pursue 
surgery and this is discussed by phone without an additional clinic visit 
they will be approached on the day of surgery by our research staff. 
 
Each patient will be provided with a paper copy of the consent form at 
their pre-operative assessment to review and sign for their participation in 
the study.  
 
23.0 Local Number of Subjects 
N = 120 (for knee arthroscopies); 60 in each arm 
N = 120 (for ACL reconstructions); 60 in each arm 
 
24.0 Confidentiality 
N/A 
 
25.0 Provisions to Protect the Privacy Interests of Subjects 
Confidentiality of patient information will be maintained using a secure, 
password-protected web portal and database. This database will be de-

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identified.  Access to this database will only be available to members of 
Dr. Tjong’s research team.  Identifying information will be kept separately 
in a password-protected desktop database or locked-file drawer.  Subjects’ 
privacy interest will be maintained as they will only interact with or 
provide sensitive information to members of Dr. Tjong’s research team 
after they have confirmed interest in enrolling in the study.   
 
Efforts will be made to make subjects feel at ease with the research by 
explaining risks and benefits of participation in the study.  A member of 
Dr. Tjong’s research team will explain the preoperative questionnaire and 
the post-operative phone call. 
 
Dr. Tjong’s team only has permission to access the subjects’ medical 
records for research purposes after they have provided informed consent to 
enroll in the study.   
 
26.0 Compensation for Research-Related Injury 
N/A 
 
27.0 Economic Burden to Subjects 
There may be the possibility that there will be a greater expense to subjects who 
are in ACL-Group 1 as they will be required to pay for two times the number of 
pain pills. However, for patient's paying cash, the cost for 30 and 60 Norco at the 
Northwestern Walgreens are $31.49 and $56.99 respectively. This discrepancy 
will likely be less for those with prescription insurance. Some patients are 
prescribed 60 Norco as standard of practice so those being prescribed 30 are 
incurring less of an expense. This could potentially be somewhat of a benefit of 
the study. 
 
28.0 Consent Process 
Each subject enrolled in the study will provide informed consent for 
participation in the study.   
 
Informed consent will initially take place during initial contact with 
potential subjects in the orthopedic surgery clinic. Risks, benefits, and 
alternatives of participation in the study as well as the ability to withdraw 
participation at any time will be discussed with the eligible subject.  
Understanding of these aspects of the study as well as whether the 
potential subject would like to enroll in the study will be confirmed over 
the phone. 
 
The study will follow “SOP: Informed Consent Process for Research 
(HRP-090).”  
 
29.0 Process to Document Consent in Writing 

PROTOCOL TITLE: Knee arthroscopy and ACL reconstruction RCT study 
 
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This study will be following: “SOP: Written Documentation of Consent 
(HRP-091).  
 
30.0 Drugs or Devices 
N/A