An Open-Label Randomized Noninferiority Clinical Trial of the Adductor Canal Catheter for Pain Control Post-Total Knee Arthroplasty
Phase: NA
Conditions: Total Knee Replacement Surgery
Sponsor: Kaiser Permanente

 
 
 
ACCESS 
The Adductor Canal Catheter 
Effectiveness and Safety Study 
 
 
 
 
 
An Open-Label Randomized Noninferiority Clinical Trial of the Adductor 
Canal Catheter for Pain Control Post-Total Knee Arthroplasty 
 
 
 
 
Conducted at: 
Kaiser Permanente Northern California 
San Leandro Medical Center 
Division of Research 
 
 
 
 
Sponsored by: 
The Permanente Medical Group 
Delivery Science Grants Program 
(clinicaltrials.gov Identifier pending) 
 
 
 
 
 
Protocol version 1.2 
 
March 26, 2024

TABLE OF CONTENTS 
0.0 
SCHEMA ..............................................................................................................4 
0.1 
ACRONYMS USED IN THIS PROTOCOL .......................................................... 5 
1.0 
INTRODUCTION 
1.1 
STUDY RATIONALE ............................................................................... 6 
1.2 
BACKGROUND ....................................................................................... 6 
1.3 
STUDY DESIGN ...................................................................................... 7 
2.0 
OBJECTIVES 
2.1 
PRIMARY OBJECTIVE ........................................................................... 8 
2.2 
SECONDARY OBJECTIVES ................................................................... 8 
2.3 
PROPOSED SUBGROUPS ..................................................................... 8 
3.0 
STUDY PARTICIPANTS 
3.1 
INCLUSION CRITERIA ........................................................................... 9 
3.2 
EXCLUSION CRITERIA .......................................................................... 9 
3.3 
RANDOMIZATION ................................................................................... 9 
3.4 
REFUSAL/REJECT LOG ...................................................................... 10 
3.5 
RECRUITMENT ..................................................................................... 10 
3.5.1 CLINICAL PERSONNEL AND SITE .......................................... 10 
3.5.2 RECRUITMENT STRATEGY AND MECHANISM ...................... 10 
3.6 
PARTICIPANT COMPENSATION ......................................................... 10 
4.0 
MEASUREMENTS 
4.1 
PRIMARY OUTCOME ........................................................................... 10 
4.2 
SECONDARY OUTCOMES ................................................................... 11 
4.3 
OTHER MEASUREMENTS ................................................................... 11 
5.0 
INTERVENTIONS 
5.1 
ACTIVE AND CONTROL CONDITIONS ................................................ 11 
5.2 
STUDY DEVICE .................................................................................... 11 
5.2.1 SOURCE AND MANAGEMENT OF DEVICE ............................. 12 
5.3 
CONCOMITANT MEDICATIONS AND RESTRICTIONS ....................... 12 
5.4 
ADHERENCE MEASURES ................................................................... 12 
6.0 
STUDY PROCEDURES 
6.1 
INITIAL CONTACT ................................................................................ 12 
6.2 
TELEPHONE SCREENING AND CONSENT CALL .............................. 13 
6.3 
PREOP TELEPHONE CALL ................................................................. 13 
6.4 
DAY OF SURGERY ............................................................................... 13 
6.5 
2-DAY FOLLOW-UP TELEPHONE CALL ............................................. 13 
6.6 
1-WEEK FOLLOW-UP TELEPHONE CALL ...........................................14 
6.7 
2-WEEK CLOSEOUT TELEPHONE CALL.............................................14 
6.8 
24-WEEK DATA EXTRACTION .............................................................14 
6.9 
VISIT WINDOWS ....................................................................................14 
7.0 
ADVERSE EVENT REPORTING 
7.1 
CLASSIFICATION OF ADVERSE EVENTS .......................................... 14 
7.2 
REPORTING OF SERIOUS ADVERSE EVENTS .................................. 15 
7.3 
REPORTING OF NON-SERIOUS ADVERSE EVENTS ......................... 15 
7.4 
CRITERIA FOR TREATMENT DISCONTINUATION ............................. 15 
7.5 
CRITERIA FOR PARTICIPANT STUDY WITHDRAWAL ....................... 15 
8.0 
STATISTICAL AND DATA CONSIDERATIONS 
8.1 
POWER CALCULATIONS .................................................................... 15 
8.2 
STATISTICAL ANALYSIS PLANS ........................................................ 17 
8.3 
DATA QUALITY CONTROL .................................................................. 18 
8.4 
DATA AND SAFETY MONITORING PLAN ........................................... 18 
9.0 
ETHICAL CONSIDERATIONS 
9.1 
INFORMED CONSENT ......................................................................... 18 

9.2 
PROCEDURES FOR OBTAINING CONSENT .......................................18 
9.3 
CONFIDENTIALITY ................................................................................19 
10.0 
STUDY ADMINISTRATION 
10.1 
ORGANIZATIONAL CHART ..................................................................19 
10.2 
CLINICAL SITE: KPNC SAN LEANDRO MEDICAL CENTER ...............20 
10.3 
DATA COORDINATING CENTER: KPNC DIVISION OF RESEARCH . 20 
11.0 
REFERENCES .................................................................................................. 21 
APPENDIX 1: SCHEDULE OF EVALUATIONS ........................................................... 24 
APPENDIX 2: KEY PERSONNEL ................................................................................ 25 

4 
 
0.0 
SCHEMA 
 
TITLE: 
Adductor Canal Catheter Effectiveness and Safety Study (ACCESS) 
PRIMARY 
OBJECTIVE: 
Compare the effect of usual care with an adductor canal catheter (ACC) 
containing ropivacaine to the effect of usual care without an ACC on the second- 
postoperative-day pain levels among patients undergoing elective primary 
unilateral total knee arthroplasty (TKA) 
SECONDARY 
OBJECTIVES: 
Among a sample of patients undergoing elective primary unilateral TKA who 
receive peri-articular anesthetic injections: 
1) To compare the overall two-week levels of postoperative pain between those 
participants randomized to ACCs containing ropivacaine and those participants 
randomized to usual care without an ACC 
2) To compare the use of opioid medications (in mean total morphine milligram 
equivalents) between those participants randomized to ACCs containing 
ropivacaine and those participants randomized to usual care without an ACC 
over the two-week postoperative period 
3) To describe the incidence of complications related to ACC placement including 
infection, displacement, ACC-related clinic or emergency department (ED) visits 
 
4) To conduct exploratory analyses to identify candidate predictors of differential 
response to the ACC 
 
DESIGN: 
Randomized, open-label, two-arm, parallel-comparison noninferiority trial 
 
POPULATION: 
Adults aged >18 years intending to undergo elective primary unilateral TKA at the 
KPNC San Leandro Medical Center 
 
INTERVENTION: 
Participants will be randomized to one of two treatment arms: 
▪ 
Adductor canal catheter placement in the pre-operative area immediately 
prior to TKA surgery 
OR 
▪ 
No adductor canal catheter placement 
 
DURATION: 
The intervention phase will occur between randomization and three days 
postoperatively (or until the ACC is removed by the participant or the ACC falls 
out spontaneously among ACC-randomized participants); the primary outcome 
will be measured on postoperative day 2, secondary pain and medication 
outcomes will be collected for two weeks postoperatively and the electronic 
medical record (EMR) will be examined for evidence of adverse events at 3 
months postoperatively 
 
SAMPLE SIZE: 
132 participants randomized using balanced allocation to the two study arms 

5 
 
0.1 
ACRONYMS USED IN THIS PROTOCOL 
 
ACB = Adductor Canal Block 
ACC = Adductor Canal Catheter 
ACCESS = Adductor Canal Catheter Effectiveness and Safety Study 
AE = Adverse Event 
DOR = Division of Research 
DSM = Data and Safety Monitor 
ED = Emergency Department 
EMR = Electronic Medical Record (KPNC HealthConnect) 
ERAS = Enhanced Recovery After Surgery 
ICH = International Council for Harmonization 
IDE = Investigational Device Exemption 
IND = Investigational New Drug 
IRB = Institutional Review Board 
KPNC = Kaiser Permanente, Northern California 
MCID = Minimum Clinically Important Difference 
NRS = Numerical Rating Scale 
NSAID = Non-Steroidal Anti-Inflammatory Drug 
PAI = Peri-Articular Injection 
PHI = Protected Health Information 
PROMIS = Patient-Reported Outcomes Measurement Information System 
RCT = Randomized Clinical Trial 
SAE = Serious Adverse Event 
SLN = San Leandro (KPNC Medical Center) 
TKA = Total Knee Arthroplasty 
UP = Unanticipated Problem 

6 
 
1.0 
INTRODUCTION 
 
1.1 
STUDY RATIONALE 
Pain management for patients undergoing TKA is central to the successful recovery of patients 
from surgery. In the past, pain control has relied heavily on the use of opioid analgesics, which have 
resulted in serious medical and chemical-dependency problems. In an effort to reduce the use of 
postoperative opioid medications, multi-modal (non-opioid) analgesic techniques have emerged in 
recent years, including the use of peri-articular anesthetic injections. An additional technique in 
widespread use is the adductor canal catheter, a medical device that consists of a tunneled catheter 
connected to an analgesic solution-containing reservoir that slowly infuses the anesthetic over the first 
2-3 postoperative days. 
Despite its widespread use, the incremental benefit of the ACC beyond the other widely used 
analgesic methods is poorly understood. Since its use is associated with known risks (such as 
bleeding and patient anxiety if it falls out spontaneously) and high expense, objective data regarding 
the value of the ACC is urgently needed in order to make rational, evidence-based decisions about 
whether use of the ACC should be promoted or discouraged. To address this important evidence 
deficiency, The Permanente Medical Group is funding this clinical trial to better understand the proper 
role of the ACC in the optimal postoperative care of patients undergoing TKA. 
 
1.2 
BACKGROUND 
TKA is a successful treatment option for end-stage arthritis of the knee. With an aging 
population and expanding indicated age-range, the annual volume of TKA surgery in the United States 
currently exceeds 600,000 cases and is projected to continue to increase over the next decade (1,2). 
Within Kaiser Permanente, we perform over 7,000 TKAs annually in Northern California alone. 
Published success rates following TKA surgery vary depending on the definition of success but patient 
satisfaction rates of at least 80% are typical (3). While causes of dissatisfaction following TKA surgery 
are varied, pain is the most common reported reason (4). Further, published data reported from our 
own institution has found that the most frequent cause of early inpatient readmission and ED visits after 
TKA surgery is pain (5). Pain is also one of the primary reasons patients are unable to be discharged 
home directly after surgery in our institution. 
The last decade has seen several significant advances in the management of pain following 
TKA surgery. “Multi-modal anesthesia” protocols have been developed to utilize non-opioid therapies 
during the recovery period (6). Historically TKA patients were prescribed Patient-Controlled Analgesia 
machines to self-administer parenteral opioid-based pain medication. While their use enabled patients 
to take control of their pain medication administration, the negative impact of these parenteral opioids – 
including dizziness, nausea, vomiting and respiratory depression – on their recovery after surgery has 
been well-described (7,8). 
Neuraxial and regional anesthetic techniques have been utilized in an effort to decrease 
reliance on opioid medications. While femoral nerve blocks were historically used in the management of 
post-op pain in lower extremity surgery, the block of the motor component of the femoral nerve resulted 
in reports of quadriceps weakness resulting in inability to work with therapy, delayed discharge to home 
and inadvertent falls (9,10). Adductor canal blocks (ACB) and catheters (ACC) have been described to 
provide a blockade to the entirely sensory saphenous nerve, as well as the vastus medialis nerve and 
the posterior branch of the obturator nerve without impacting the motor branches of the femoral nerve. 
These blocks offer an anterior and medial-based sensory blockade of the knee (11). The use of 
ACCs/ACBs has allowed for complete participation in post-operative rehabilitation with far fewer reports 
of quadriceps weakness (12). ACCs and ACBs have seen widespread adoption throughout Kaiser 
Permanente in the last 2 years with all but one facility in Northern California utilizing them. 
In the case of an ACC, a dedicated anesthesia provider uses a portable ultrasound machine to 
position the catheter prior to surgery in the pre-op area or after surgery in the post-anesthesia care unit. 
Once the catheter is placed, it is attached to a pump and reservoir containing 450 cc of 0.2% 
ropivacaine solution which, when activated, releases the medication in a controlled fashion. The rate of 
administration can be adjusted by the patient. Currently these catheters are left in place for 3 days after 
surgery and are then removed by the patient at home. While the quadriceps weakness associated with 

7 
 
femoral nerve blocks and catheters is largely avoided in the use of adductor canal catheters, the use of 
ACCs is not without potential complications (13). 
Another modality described for the management of post-op pain following TKA surgery has 
been the peri-articular injection (PAI) – an intra-operative injection into the peri-articular soft tissue of 
bupivacaine, epinephrine, clonidine and ketorolac (14). Its use in TKA surgery coincided with adoption 
of Enhanced Recovery After Surgery (ERAS) protocols in which early mobility and alternatives to opioid 
therapy are employed. The impact of both the PAI and ERAS protocols in TKA patients’ outcomes have 
been well-described (15–17). PAI use in TKA surgery is now nearly universal within Kaiser Permanente 
and is considered one of the modalities which satisfies the ERAS metric of multi-modal pain 
management in elective TKA. 
In 2016, CMS initiated the Comprehensive Care of Joint Replacement program to help reduce 
the costs associated with a total knee or hip replacement. This program shifted the reimbursement 
model for total hip and knee replacement surgery from one of fee-for-service to one of a single 
reimbursement for the entire episode of care. The introduction of this “bundled payment” 
reimbursement model has resulted in a renewed focus on all costs related to the total joint care 
pathway and has had a direct impact on the reduction of length of inpatient stay following total joint 
arthroplasty across the nation. 
Inpatient hospital admission is one of the greatest contributors to the cost of the episode of care. 
In the last 7 years we have seen our length of stay for total knee replacement patients reduced from 3 
days to less than one day. One of the major hurdles in safe patient discharge after TKA surgery is 
adequate pain control. The adoption of a multi-modal pain reduction strategy and, in particular, the use 
of the peri-articular injection has facilitated this reduction in LOS. Part of the rationale for the addition of 
adductor canal catheters to this pain-reduction strategy is to help improve post-operative pain and 
reduce LOS. In KPNC SLN, where we perform over 1,000 primary unilateral TKA surgeries each year, 
utilization of ACCs is variable among surgeons. Comparing length of stay in our primary TKA patients, 
we see the same rate of same day discharge among providers who use ACCs and those who do not. 
Further, a pilot study conducted at our facility in 2018 found only a very small (and clinically 
unimportant) difference in post-operative day 2 (when the effects of the PAI would be expected to have 
worn off) numerical pain score between patients with an ACC and those without. These findings are 
similar to a recently published randomized control study which found no difference in pain levels or 
opioid consumption between TKA patients with PAI alone or with PAI plus ACB (18). Our pilot study 
has also identified several complications associated with ACCs including leaking, dislodging, bleeding, 
hematoma development and prolonged neuropraxia, resulting in ED visits and phone calls to address 
these issues. 
The entire cost of adductor canal catheters includes the pump, tubing and medication as well as 
the FTE provider who places them and the potential cost of ED visits or phone calls/office visits to 
address complications associated with the catheters. Given the cost of the catheters themselves ($400) 
and the number of primary TKA surgeries performed annually in KPNC alone (> 7,000), the annual cost 
to our organization is estimated to be more than $4 million. 
Therefore, we propose this randomized, open-label, parallel-comparison noninferiority clinical 
trial to determine whether the effectiveness of these catheters justifies their cost. 
 
1.3 
STUDY DESIGN 
This is a randomized, open-label, two-arm, parallel-comparison noninferiority clinical trial of 
usual care with an ACC placed preoperatively compared to usual care without an ACC among adult 
patients undergoing elective unilateral TKA at the KPNC San Leandro Medical Center (Figure). 
All patients meeting eligibility criteria will be introduced to the study by the treating orthopedist 
and PI, Dr. Adrian Hinman, at the patient's first clinic visit. If the patient expresses interest in study 
participation, they will be consented over the phone by the clinic Physician's Assistant (PA). Baseline 
data will be obtained via a telephone call with the study Research Assistant 7-10 days prior to the date 
of surgery. Randomization will occur in the preoperative area immediately prior to surgery. Patients will 
keep a daily diary of their pain levels and analgesic medication use for two weeks postoperatively and 
will be called by the study Research Assistant on post-op day two and day 14. A single electronic 

8 
 
medical record (EMR) data extraction for adverse events (focusing on emergency department and 
inpatient visits) will be conducted at 30 days postoperatively. 
The primary outcome is the absolute pain score on post-op day two, measured on an 11-point 
numerical rating scale; the noninferiority margin for this comparison is set a priori at 2.0 points. 
Secondary outcomes include the total amount of opioid consumed over the two-week post-op period, 
the overall pain scores over the two-week post-op period, and adverse events directly attributed to the 
ACC. 
 
 
 
First Clinic 
Visit 
Telephone 
Consent 
Randomi- 
zation / TKA 
Postop 
Day 2 
NRS 
Postop 
Day 14 
Call 
Postop Day 30 
EMR Data 
Extraction 
 
Figure: Study Design Schema 
 
 
2.0 
OBJECTIVES 
 
2.1 
PRIMARY OBJECTIVE 
To compare the effect of usual care with an ACC containing ropivacaine to the effect of usual 
care in the absence of an ACC on the second-postoperative-day pain levels among patients 
undergoing elective primary unilateral TKA who receive peri-articular anesthetic injections 
 
2.2 
SECONDARY OBJECTIVES 
Among a sample of patients undergoing elective primary unilateral TKA who receive peri- 
articular anesthetic injections: 
1) To compare the overall two-week levels of postoperative pain between those participants 
randomized to ACCs containing ropivacaine and those participants randomized to usual care without 
an ACC 
2) To compare the use of opioid medications (in mean total morphine milligram equivalents) 
between those participants randomized to ACCs containing ropivacaine and those participants 
randomized to usual care without an ACC over the two-week postoperative period 
3) To estimate the incidence of complications related to ACC placement including infection, 
displacement, ACC-related outpatient clinic or ED visits 
4) To conduct exploratory analyses to identify candidate predictors of differential response to 
the ACC; potential interacting variables for these analyses will include demographics, baseline pain 
NRS scores, clinical comorbidities and secondary outcome measures. 
 
2.3 
PROPOSED SUBGROUPS 
No subgroup analyses are proposed for this trial. As noted above (2.2, Secondary Objective 
#4), we will conduct exploratory analyses of potential interacting variables associated with differential 
(positive) response to the use of the ACC. As exploratory investigations, it is acknowledged that these 
analyses will likely be underpowered and are hypothesis-generating only. 
 
 
3.0 
STUDY PARTICIPANTS 
ACC 
 
 
NO ACC 

9 
 
3.1 
INCLUSION CRITERIA 
All study participants will be active members of the KPNC health plan, since all recruitment 
activities and interventions will take place in KPNC medical facilities. 
The inclusion criteria for the ACCESS study, and their rationales, are: 
 
1. Age > 18 years 
1. Age of consent 
2. Intending to undergo elective primary 
unilateral TKA at the KPNC SLN Medical 
Center 
2. Indication for use of the ACC; study site 
is KPNC SLN Medical Center 
3. Patient ambulates independently 
3. Non-ambulatory patients may have 
atypical postoperative recovery courses 
 
 
3.2 
EXCLUSION CRITERIA 
The exclusion criteria for the ACCESS study, and their rationales, are: 
 
1. Patient declines use of ACC 
1. Patient not eligible for ACC study arm 
2. Surgeon decides that an ACC will not be placed 
for any reason 
2. Patient not eligible for ACC study arm 
3. Known hypersensitivity to ropivacaine or any 
alternative anesthetic for ACC use 
3. Patient not eligible for ACC study arm 
4. Hypersensitivity or inability to tolerate peri- 
articular injections of clonidine, epinephrine, 
bupivacaine and ketorolac 
4. Participants in both arms of the trial 
are required to undergo peri-articular 
anesthetic injections 
5. Any evidence of substance-use disorder in past 
year 
5. Opioid use is a secondary study 
outcome measure 
6. Non-English speaking 
6. Study instruments are all in English 
7. Failure to complete all baseline study 
instruments prior to surgery 
7. No baseline measurement available 
for calculating change 
8. Requires secondary procedure at time of TKA 
(e.g., removal of hardware) 
8. Complex surgery may cause change 
in outcome measures independent of 
study objectives 
9. Not intending to use spinal anesthesia for TKA 
procedure 
9. Atypical surgical approach 
10. Actively enrolled in KPNC chronic-pain 
program 
10. Opioid use is a secondary study 
outcome measure 
11. Having been prescribed long-acting opioid 
(e.g., Oxycontin, MS Contin) within 90 days prior 
to enrollment 
11. Pre-surgery major opioid use may 
complicate measurement of post- 
surgery opioid use 
12. Inability to tolerate any oral NSAID or 
acetaminophen or any short-acting opioid 
12. NSAIDs, acetaminophen, and short- 
acting opioids are used for analgesia for 
all participants 
 
These exclusion criteria are established for safety and to ensure consistency in the participant 
sample. 
 
3.3 
RANDOMIZATION 
Randomization will be balanced (i.e., using an allocation ratio of 1:1) and blocked (using 
randomly chosen block sizes of 2, 4, and 6); no stratified randomization will be used. 
The randomization list will be generated by Dr. Catherine Lee (study Biostatistician) using the 
“ralloc.ado” procedure in Stata (this procedure creates a balanced, blocked, and self-documenting 
randomization list) (19). The randomization list will then be used by study staff to create a set of 
sequentially numbered, sealed opaque envelopes which contain cards on which the randomization 

10 
 
assignment for each study participant is noted (the cards will be covered in aluminum foil inside the 
envelopes to defeat "hot-lighting" the envelopes). A copy of the randomization list will be given to a 
DOR investigator who is not affiliated with the ACCESS study, as backup in case the randomization 
envelopes are misplaced or stolen, and as validation for any study audits. 
The randomization envelopes will be stored in a locked box that will be stored in a locked 
cabinet in the pre-op area, accessible only to appropriate study personnel. As noted above, 
randomization will occur in the pre-operative area prior to the participant being transported to the 
operating room for their surgery. 
 
3.4 
REFUSAL/REJECT LOG 
A log of potential participants who decline to enter the study or who are deemed ineligible by the 
application of entry inclusion and exclusion criteria will be kept in order to judge the representativeness 
of those who consent to be randomized, consistent with CONSORT guidelines (20). If the individual 
and the IRB permits, data collected in the refusal/reject log will include the individual’s age, gender, 
race/ethnicity, NRS pain score, and reason for rejection or refusal. 
 
3.5 
RECRUITMENT 
 
3.5.1 CLINICAL PERSONNEL AND SITE 
Participants will initially be recruited from Dr. Hinman's TKA patient list at KPNC San Leandro. If 
recruitment lags behind a priori goals, it will be expanded to include the TKA patients of other San 
Leandro orthopedists (Drs. Kasey Cortese and David Lee have agreed to complete their research 
trainings and participate in patient recruitment should Dr. Hinman's patients be insufficient to maintain 
recruitment at the required levels). KPNC San Leandro will remain the only clinical site; no patients will 
be recruited from any other KPNC facility. 
 
3.5.2 RECRUITMENT STRATEGY AND MECHANISM 
Patients will first be notified of the existence of the study by Dr. Hinman (or another participating 
orthopedic surgeon) at their first clinic visit. After it has been determined that TKA is indicated and the 
patient is intending to undergo surgery, the orthopedist will briefly introduce the study to the patient. 
Unless the patient expresses clear disinterest in participating in the trial, they will be given an ACCESS 
clinic introductory packet by the clinic Patient Navigator along with their usual pre-operative preparation 
materials. This packet will contain the following items: informational materials about the ACCESS trial, 
two copies of the unsigned consent form, two copies of the unsigned HIPAA authorization form, one 
copy of the Research Subject's Bill of Rights, the baseline questionnaire, and a postage-paid reply 
envelope. An appointment will be made with the study Physician's Assistant for a telephone 
information-and-consent call with the patient. 
 
3.6 
PARTICIPANT COMPENSATION 
Participants will be compensated $50 for completing all study procedures including all pre- 
randomization activities, proceeding through randomization, and completing their post-operative data 
collection including the pain/medication diary and study-related telephone calls. Payment will be made 
in the form of a gift card to a commercial retail store (typically Target, Safeway, or Amazon). 
 
 
4.0 
MEASUREMENTS 
 
4.1 
PRIMARY OUTCOME 
The primary outcome measurement for this study is the Numerical Rating Scale for pain 
recorded on the second postoperative day. The pain NRS is a 0-to-10 ordinal scale (with anchors, 0 = 
"no pain" and 10 = "worst possible pain") which the participant selects in response to the prompt, "What 
number best describes your typical pain in the past 24 hours?". Several different variations of pain- 
intensity measures exist but there is good evidence that numerical rating scales are easy to administer 

11 
 
with high respondent acceptability, high reliability (21,22), excellent validity when compared to visual 
analogue scales (21) and widely recommended as a core measure in pain trials (23). 
The primary outcome will be obtained by the study Research Assistant via a telephone call on 
the second postoperative day. If the Research Assistant is unable to reach the participant by phone, 
the pain NRS score for the second postoperative day on the daily diary will be used for this 
measurement, if the diary is returned to the DOR. 
 
4.2 
SECONDARY OUTCOMES 
Originally, the secondary outcomes included the PROMIS Global Health-10 short form and the 
Knee injury and Osteoarthritis Outcome Score short form (KOOS Jr). However, after further 
reflection among the study investigators, it was decided that these measures of symptoms and 
functions provided little meaningful outcome data among a sample of patients soon after knee 
replacement. Therefore, these measures were discarded as secondary outcome 
measurements. 
 
However, the investigators decided that consumption of opioid medication in the 15 days 
postoperatively (as provided in the postoperative pain-and-medication diary) provided an 
important and meaningful secondary outcome measure for assessing the analgesic 
effectiveness of the ACC. The main secondary outcome measure will be the total number of 
5mg oxycodone tablets (provided to all patients on discharge) consumed over the 15-day 
postoperative period.  This change is reflected in the study schema, above. 
 
4.3 
OTHER MEASUREMENTS 
In addition to these instruments, we will also collect data on patient demographics, clinical 
history of knee pain (approximate length of time with symptoms, prior interventions, history of ipsilateral 
knee trauma, etc.), prior medication use, and relevant comorbidities (e.g., gout, inflammatory arthritis). 
 
 
5.0 
INTERVENTIONS 
 
5.1.1 
ACTIVE AND CONTROL CONDITIONS 
Participants in the intervention arm will have implanted a bupivacaine-filled ACC immediately 
prior to surgery, according to usual preoperative-care practices (for the patients of those orthopedists 
who use the catheters). As a pragmatic trial, there will be no change in the nature of the device or the 
manner in which it is implanted and managed postoperatively. All other aspects of pre-surgical, 
operative, and post-operative care will be conducted as per usual clinical practice. 
Participants in the control arm will receive identical clinical care with the exception that no ACC 
will be placed in their leg prior to surgery. 
 
5.1 
STUDY DEVICE 
The adductor canal catheter is a device which is placed by a trained anesthesia provider in 
order to apply analgesia to the anterior portion of the knee. It consists of a catheter, tubing and an 
adjustable time-release pump and reservoir. The reservoir is filled with 450 ccs of 0.2% ropivacaine. 
The catheter is inserted into the adductor canal, which contains the purely sensory saphenous nerve - a 
branch of the femoral nerve which supplies the anterior portion of the knee. The pump releases the 
ropivacaine in a controlled release fashion over 48-72 hours depending on the adjustable rate of the 
pump. When the reservoir is empty, the catheter is removed by the patient and disposed. 

12 
 
5.1.3 SOURCE AND MANAGEMENT OF DEVICE 
The ACC is an FDA-approved medical device in current use within KPNC. The device is 
considered a standard-of-care instrument and, therefore, does not require special handling for use in a 
research study. The ACCs used for this study will be stored in the usual hospital locations and be filled 
with the bupivacaine anesthetic by the hospital pharmacist, in the usual manner. The device will be 
placed in the legs of the intervention-allocated patients by a KPNC anesthesiologist according to usual 
clinical practice and it will be removed by the patient by postoperative day three, according to the 
manufacturer's instructions. The device will be discarded by the patient at home and not be returned for 
study purposes. 
 
5.1.4 CONCOMITANT MEDICATIONS AND RESTRICTIONS 
All patients will receive periarticular anesthetic injections at the time of surgery. Postoperatively, 
all patients will receive a standard set of oral analgesic medications for pain control. These medications 
include ibuprofen 600 mg orally every 8 hours, acetaminophen 1 gm orally every 8 hours and 
oxycodone 5 mg 1 tab orally every 6 hours as needed for moderate pain or 2 tabs orally every 6 hours 
as needed for severe pain not relieved by other analgesics (patients also receive aspirin 81 mg orally 
twice daily for venous thromboembolism prophylaxis). Use of analgesic medications in the two weeks 
after surgery will be reported by the patient through the use of the daily patient diary (for those patients 
who are not discharged to home on the same day of surgery, we will also obtain data on the analgesic 
medications given to the patient while in the hospital). As a pragmatic trial, patients are free to use any 
recommended postoperative services, such as physical therapy in mind-body techniques for pain 
management. 
 
5.1.6 
ADHERENCE MEASURES 
Because placement of the ACC will be carried out immediately after randomization by the 
attending anesthesiologist (for those participants randomized to receive an ACC), there is little 
opportunity for intervention non-adherence. However, It is anticipated there may be an occasional 
patient who develops "cold feet" immediately after randomization and declines the randomized 
assignment); these patients are randomized and will be asked to follow through with all other study - 
related procedures, including data collection. As the primary analysis will be intention-to-treat, 
participants will be analyzed in the group to which they were originally randomized, regardless of their 
actual adherence to the intervention. 
Most data collection will occur in the two postoperative weeks. Both the baseline and closeout 
questionnaires will be administered over the phone, to help ensure completeness of data collection. All 
participants will be asked to complete a daily pain and medication diary which they will return to the 
Division of Research, where their data will be entered into a REDCap database with full range and logic 
checking. All patients will be called two days after surgery (for collection of the primary pain NRS 
outcome measurement), one week after surgery to encourage adherence with data collection, and 
again 14 days after surgery for completion of the closeout questionnaire and a reminder to return the 
daily diary to the DOR. Regular reports of the completeness of data collection will be generated and 
reviewed by all study personnel on a regular basis to ensure high quality of data collection. Any 
evidence of problems in data collection or quality will be addressed quickly and monitored carefully. 
 
 
6.0 
STUDY PROCEDURES 
 
6.1 
INITIAL CONTACT 
Patients' first introduction to the ACCESS study will occur during their first visit with their 
orthopedist during which the decision regarding proceeding to TKA will occur. Using an IRB-approved 
script, the orthopedist will briefly describe the rationale and essential details of the study. The patient 
will be encouraged to ask questions and, if the patient expresses interest in learning more about the 
study, the orthopedist will inform the Patient Navigator. 

13 
 
After the patient's visit with their orthopedist, the Patient Navigator will hand to the patient a 
packet containing: informational materials about the ACCESS trial, two copies of the unsigned consent 
form, two copies of the unsigned HIPAA authorization form, one copy of the Research Subject's Bill of 
Rights, the baseline questionnaire, and a postage-paid reply envelope. An appointment will be made 
with the study Physician's Assistant for a telephone information-and-consent call with the patient. 
 
6.2 
TELEPHONE SCREENING AND CONSENT CALL 
At the appointed time, the study PA will call the patient at home and present the study details to 
the patient using an IRB-approved script and answer any questions the patient may have. If the patient 
expresses a desire to enroll in the study, the PA will ask the patient to retrieve the consent and HIPAA 
Authorization forms from the clinic study packet; the PA will then walk through all elements of the 
consent form with the patient, again using an IRB-approved telephone script. If, after this procedure, 
the patient is still interested in enrolling in the study, they will sign their copy of the consent form. The 
same procedure will then be repeated for the HIPAA authorization form. The PA will then ask the 
patient to put both sign forms in the postage-paid reply envelope and mail them back to the orthopedics 
department at the SLN Medical Center. The PA will document this call in the patient's medical record. 
During this call and after the consent is obtained, the PA will also conduct an eligibility screen to 
ensure that the patient meets all inclusion and none of the exclusion criteria; these will be documented 
in the study screening form. 
 
6.3 
PREOP TELEPHONE CALL 
Approximately one-week prior to the participants TKA surgery, the study Research Assistant will 
call the patient at home to ensure that they are still intending to follow through with all study procedures 
and to ensure they understand the details of their further participation, including the randomization 
immediately prior to surgery. If the patient has any questions, they will be referred to the DOR co-PI 
(Dr. Avins) for further discussions. If the patient expresses any reservations about their further 
involvement in the study, they will not be randomized. If the patient is fully intending to continue with 
the study, the RA will administer the baseline questionnaire over the phone before ending the call. 
During this call, the RA will also conduct a repeat eligibility screen to ensure that the patient 
meets all inclusion and none of the exclusion criteria. 
 
6.4 
DAY OF SURGERY 
On the day of surgery, all preoperative activities will proceed as usual for patients undergoing 
TKA at the SLN Medical Center. The orthopedic surgeon, when meeting with the patient prior to 
surgery, will confirm once more that the patient is intending to be randomized and participate in the 
study. Note that there will be no additional consent procedure (as advised by the regulatory specialist 
with the KPNC DOR Clinical Trials Unit). 
At the time when an ACC would normally be placed by the anesthesiologist (if the patient was 
going to have an ACC placed), the orthopedist or study PA will obtain the next consecutive 
randomization envelope and open it, revealing to the patient and anesthesiologist the randomization 
assignment. If the participant is randomized to placement of the ACC, the anesthesiologist will proceed 
with ACC placement as usual. If the participant is randomized to non-placement of the ACC, no ACC 
will be inserted and the remaining preoperative activities will continue as usual. 
After surgery (whether the participant will be discharged to home on the day of surgery or 
admitted to the hospital), the patient will be given a packet containing all instructions for further 
participation, their daily pain-and-medication diary, and the closeout questionnaire). They will be told to 
begin filling out their diary the following day. 
 
6.5 
2-DAY FOLLOW-UP TELEPHONE CALL 
On the afternoon of the second postoperative day, the study Research Assistant will call the 
participant at home to obtain their numerical rating pain score for the primary study outcome. They will 
inquire of the patient if they have any questions regarding their further participation, ensure that the 
participant understands their research-related responsibilities, and encourage adherence with all data 

14 
 
collection. Note that this call is separate from any clinical telephone calls made to the participant from 
the orthopedics department. 
 
6.6 
1-WEEK FOLLOW-UP TELEPHONE CALL 
One week following the date of surgery, the study Research Assistant will call the participant at 
home to ensure that they are continuing to fill out their daily participant diary, inquire about any potential 
adverse events, answer any questions, and remind the patient that there will be a closeout phone call in 
another week. 
 
6.7 
2-WEEK CLOSEOUT TELEPHONE CALL 
Two weeks after the date of surgery, the study Research Assistant will call the participant at 
home and conduct the closeout interview. The RA will again inquire about any potential adverse events 
since the prior call (including follow-up of previously reported AEs), answer any questions, then conduct 
the closeout questionnaire interview. Towards the end of the call, the RA will then instruct the 
participant to place their daily diary into the postage-paid reply envelope and mail the envelope to the 
DOR as soon as possible. 
 
6.8 
24-WEEK DATA EXTRACTION 
Approximately 24 weeks after surgery, the study programmer will extract relevant clinical 
information from Clarity, primarily for the purpose of assessment for evidence of SAE's between two 
and 24 weeks postoperatively. Any evidence of potential SAE's during this time will be investigated by 
the DOR co-PI and reported in accordance with regulatory requirements. 
 
6.9 
VISIT WINDOWS 
The following lists the follow-up visit windows outside of which data collection will be considered 
a protocol deviation: 
One-week preoperative telephone call: Ten days prior and four days following 
2-day follow-up telephone call: No window 
1- week follow-up telephone call: No data collection at this call 
2- week closeout telephone call: Two days prior and three days following 
24-week data extraction: Two months following the 24-week timepoint (data will be collected 
only for the period from surgery to 24 weeks postoperatively 
 
7.0 
ADVERSE EVENT REPORTING 
 
7.1 
CLASSIFICATION OF ADVERSE EVENTS 
The ACCESS study uses the definitions of an adverse event (AE) and a serious adverse event 
(SAE) established by the International Conference on Harmonization (ICH) guidelines on Clinical Safety 
Data Management (32). These definitions are: 
An adverse event (also known as “non-serious adverse event” (NSAE)) is any untoward 
medical occurrence in a patient or clinical investigation subject administered a study intervention and 
which does not necessarily have a causal relationship with this treatment. An adverse event can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, 
or disease temporally associated with the use of an intervention, whether or not considered related to 
the intervention. Note that adverse changes in the outcome measures of the study (e.g., pain scores) 
are not considered adverse events and will not be reported as such. Symptoms or other abnormalities 
that were present prior to a participant's randomization will not be considered adverse events (i.e., 
these will be treated as pre-existing conditions and not-study related); similarly, therapies (e.g., surgery) 
to treat a pre-existing condition are not reportable adverse events. Note that clinically meaningful 
worsening of a pre-existing condition is considered an adverse event and will be reported as such. 
A Serious Adverse Event (SAE) is any untoward medical occurrence that: 
1) results in death 
2) is life-threatening 

15 
 
3) requires inpatient hospitalization or prolongation of existing hospitalization 
4) results in persistent or significant disability/incapacity 
5) is a congenital abnormality or birth defect 
6) is an important medical event that may not result in death, be life-threatening or 
require inpatient hospitalization but if, based on appropriate medical judgment, it may 
jeopardize the patient and may require medical or surgical intervention to prevent a 
serious adverse event. 
 
An Unanticipated Problem (UP) is a subset of adverse events with special reporting 
requirements. The definition of a UP is: 
1) It is unanticipated (in nature, severity, and/or frequency), and 
2) It is at least possibly related to participation in research, and 
3) It suggests greater risk of harm to participant(s) or others than previously known or 
recognized (includes participants, family members, and research staff). 
 
7.2 
REPORTING OF SERIOUS ADVERSE EVENTS 
While the ACCESS study will not be conducted under an FDA IND or IDE, we will observe 
similar reporting requirements, modified for compatibility with the KPNC IRB guidelines. Deadlines for 
reporting are described below. The form for reporting will be the usual ACCESS SAE report form for 
early reportable SAE's and UP's and the relevant DSM report AE/SAE table (which will also be 
forwarded to the IRB following each DSM meeting) 
 
Report to the IRB and DSM within 1 business day and at annual renewal 
Unanticipated death at least possibly related to study (i.e., fatal UP) 
Report to the IRB and DSM within 10 business days and at annual renewal 
SAE's that are UP's 
New safety information becomes available that is at the level of an UP 
Report only at annual renewal (IRB) or at each DSM meeting 
Death that is NOT a UP (i.e., all deaths that are not reported within 1 day) 
 
7.3 
REPORTING OF NON-SERIOUS ADVERSE EVENTS 
All non-serious AE’s will be recorded on the study AE form. All AE’s will be reported in 
aggregate and individually to the IRB annually and to the DSM at each scheduled DSM conference call. 
 
7.4 
CRITERIA FOR TREATMENT DISCONTINUATION 
Any ACC-allocated participant who exhibits a serious untoward reaction to the study ACC that, 
in the opinion of the investigators or the participant’s treating physician, would render study continuation 
contrary to the best interest of the participant will be withdrawn from the study intervention. Any 
participant who is withdrawn from study intervention will be encouraged to continue all study-related 
data collection, in order to permit an intention-to-treat analysis with minimal data imputation. 
 
7.5 
CRITERIA FOR PARTICIPANT STUDY WITHDRAWAL 
All participants will be encouraged to adhere to all study procedures even if they decline their 
randomized treatment assignment or prematurely remove the ACC, in order to permit an intention-to- 
treat analysis. If a participant expresses an intention to withdraw from the study prior to the two-week 
closeout time point, he/she will be questioned about the reasons for their intended withdrawal and 
attempts at resolving barriers to continued participation will be made (e.g., increasing contact with study 
investigators, shortening questionnaire time). Any participant may withdraw entirely from the study at 
any time. 
 
 
8.0 
STATISTICAL AND DATA CONSIDERATIONS 
 
8.1 
POWER CALCULATIONS 

16 
 
As a noninferiority study, this trial has been powered to ensure that the lower limit of the 95% 
confidence interval does not cross the pre-specified noninferiority margin if the null hypothesis is 
rejected. We have made several conservative assumptions to ensure that the lack of a finding of 
noninferiority is not due to a lack of statistical power: we assumed a statistical power of 95% (very high 
power to increase the likelihood that the lower bound of the one-sided 95% CI will be on the null side of 
the noninferiority margin if usual care without an ACC is truly noninferior to use of an ACC), we have 
used a one-sided 95% CI of 0.025, and the variance estimate was obtained from a sample of patients 
similar to those intended for recruitment from the SLN Medical Center. 
Special care was taken in establishing the noninferiority margin. Note that the goal of this study 
is not to demonstrate noninferiority in an absolute clinical sense, but to provide sufficient information to 
the orthopedic community in order to inform the decision regarding placement of ACC's. This insight led 
the PI (Dr. Hinman) to conduct an e-mail poll of his colleagues, asking for their perception of the MCID 
that would lead to a change in practice with respect to placing ACC's. Dr. Hinman received 19 replies 
with the following response distribution: 
0.5 points: 1 (5.3%) 
1.5 points: 2 (10.5%) 
2.0 points: 11 (57.9%) 
3.0 points: 4 (21.1%) 
4.0 points: 1 (5.3%) 
Mean: 2.18 points / Median: 2.0 points 
Given the median MCID of 2 points, we originally chose a conservative value of 1.5 points (0.5 
points below the median) for this trial, in order to maximize credibility of the results. This value was 
revised upward to 2.0 (see below) in version 1.1 of the protocol. 
The following describes the methods and assumptions used for calculation of the necessary 
sample size for this study (power calculations were performed with the PASS power-analysis package 
(33)): 
H0: The mean NRS pain score in the active-treatment group is less than the mean NRS pain 
score in the control group on the second postoperative day 
HA: The mean NRS pain score in the active-treatment group is not less than the mean NRS pain 
score in the control group on the second postoperative day 
α: 0.025 (1-tailed) [standard practice for noninferiority trials (34) 
β: 0.02 (Power=98%) 
Standard deviation = 2.64 (from an interim analysis of the blinded data of 98 enrolled 
participants) 
Noninferiority margin (δ) = 2.0 points 
Randomization ratio: 1:1 
Test on which calculations based: z-test 
Number of evaluable randomized participants required = 60 per group; Total number required = 
120 
Total number of recruited participants required accounting for 10% withdrawals = 132 (66 per 
group) 
 
This sample size will require recruitment of 132 participants/64.5 weeks = 2.1 participants per 
week (the SLN Medical Center orthopedics group performs approximately 20 TKAs per week). 
 
Note on interim data examination to resize the trial: The sample size calculations described above 
relied on an estimate of the standard deviation of the primary outcome, which was calculated using a 
sample of 163 KPNC SLN members who underwent TKA in 2018. Although we expect that the 
standard deviation of the primary trial outcome will align with the estimates used in the sample size 
calculation, deviations in the estimate used may have a substantial impact on sample size and power. 
Because of this, we plan to estimate the standard deviation of the primary outcome using interim data 
mid-way through the trial (the first 59 patients pooled from both trial arms) (35), and will re-calculate the 
sample size to ensure that our original calculations are reasonably appropriate to the observed 

17 
 
variance. Note that there is no inter-group comparison and, therefore, no cost to the experimentwise 
alpha. 
 
Note on the revised calculations: Blinded study data were examined twice, most recently after 98 
participants were enrolled and the assumed standard deviation of 2.04 was revised upward to 2.64 
based on this analysis. In addition, the survey of knee-arthroplasty specialty KPNC orthopedic 
surgeons conducted by the Principal Investigator showed that 84% of the 19 respondents would set the 
noninferiority margin at 2.0 points or more. In the original power calculations, we assumed a 
noninferiority margin of 1.5 points, in order to be highly conservative. However, after further reflection 
and sensitivity analyses, we found that adopting such a strict noninferiority margin could substantially 
impair our ability to declare noninferiority for an observed nonzero difference. Therefore, we reset the 
noninferiority margin back to 2.0 points, consistent with the responses to the orthopedist survey. 
Finally, in order to retain a very high likelihood of affirming noninferiority if the point estimate of the 
between-group difference in the outcome pain scores was less than the noninferiority margin, we 
decreased the beta to 0.02 (power = 0.98). 
 
8.2 
STATISTICAL ANALYSIS PLANS 
We will summarize baseline variables and covariate data using standard descriptive statistics 
(frequencies and proportions for categorical variables; means, standard deviations, quartiles, the 
minimum and maximum for continuous variables). This will allow us to identify baseline imbalances that 
are due to random chance and possible missing data. 
The primary analysis is a comparison of mean NRS pain scores between the two treatment 
groups at the second postoperative day. This analysis will be conducted with a linear regression model 
that includes an indicator variable for the usual care without ACC group (the test on the coefficient, 
denoted β1, of which will form the primary comparison of interest), and covariates identified as poorly 
balanced at baseline (i.e., a 20% between-group difference, in general). Note that β1 represents the 
difference in mean NRS pain score at the second postoperative day between the usual care without 
ACC group and use of ACC group, holding all other covariates fixed. The null hypothesis for the test of 
noninferiority assumes that the usual care without ACC is inferior to the use of ACC (specified in 
Section 8.1); in terms of the linear regression model, this corresponds to H0: β1≥ δ, where δ is the pre- 
specified noninferiority margin of 2.0. The alternative hypothesis assumes that the usual care with ACC 
is noninferior to the use of ACC, HA: β1<δ. Noninferiority is established at the α=0.025 level if the upper 
bound of the 95% confidence interval lies below the noninferiority margin, δ =2.0. The primary analyses 
will be conducted under the principle of intention-to-treat, which is, admittedly, controversial as some 
authorities assert that intention-to-treat is non-conservative in the setting of a noninferiority trial (36); 
missing data will be imputed using a standard multiple-imputation algorithm. As a secondary analysis, 
we will also repeat the primary analyses under a per-protocol paradigm. Finally, since the NRS is a 
fundamentally ordinal scale, we will verify the bivariate comparison with a non-parametric Wilcoxon 
rank-sum test that requires no distributional or linear-scale assumptions. All analyses will be conducted 
with updated versions of the SAS (37) and Stata (19) statistical packages. 
 
For our secondary aims, we will use the following analytic approaches: 
 
Secondary Aim 1: The first secondary analysis is a comparison of the mean NRS pain scores between 
the two treatment groups over the two-week follow-up period. We will have up to 15 measurements per 
individual (daily pain scores over a two-week period including baseline measurement). We are primarily 
interested in whether the rate of change in NRS pain score over the two-week follow-up period differs 
between the two treatment groups. These analyses will be conducted with linear mixed-effects models 
(38,39) that include terms for the effects of time, study group and the group-by-time interaction which 
will serve as the primary statistical test of the study hypothesis. Subjects will be included as random 
effects, and the within-subject correlation will be modeled appropriately. The most appropriate error 
structure will be chosen by comparing model fit using Akaike’s Information Criterion (40). The overall 
difference between two total response curves will be tested with likelihood-ratio tests. The predicted 

18 
 
(modeled) change in the outcome over the relevant follow-up period will be obtained from each model 
along with the associated standard errors from which 95% confidence intervals will be constructed. 
 
Secondary Aim 2: The mean difference in two-week postoperative opioid use (measured in total 
morphine equivalents) between the two treatment groups will be compared with a two-sample t-test. A 
secondary analysis will be conducted with a multiple linear regression model with an indicator variable 
for treatment group (for which the test of β1=0 will form the primary hypothesis test) and adjustment for 
baseline covariates, use of opioids at baseline, and baseline NRS pain score. 
 
Secondary Aim 3: The frequencies of complications related to ACC will be summarized with proportions 
and associated exact 95% confidence intervals. 
 
Secondary Aim 4: To identify candidate predictors of differential response to the ACC, we will consider 
including interaction terms between the treatment indicator and demographic variables and baseline 
pain NRS scores in the primary linear regression analysis. 
 
 
8.3 
DATA QUALITY CONTROL 
All data collected for this trial will be stored in REDCap, a secure, web-based data collection 
application that employs full range and logic checking (and that is currently in use at KPNC DOR). 
Study investigators and staff will review data reports bi-weekly to ensure that data collection is 
proceeding appropriately. Extensive pilot testing of all procedures (from recruitment to data entry) will 
be completed prior to enrolling participants into the full trial. 
Dr. Adrian Hinman, as the facility-based PI, is responsible for the overall implementation and 
conduct of the study and takes primary responsibility for all clinic-related activities. Dr. Avins, who is 
based at the KPNC DOR, will take primary responsibility for all data coordination and reporting. All 
study staff will have regular face-to-face meetings at DOR during which all issues related to study 
progress will be discussed and procedures refined and documented. The study statistician and 
programmer/analyst will prepare bi-weekly reports of all critical information including recruitment rates 
and targets, visit and intervention adherence, completeness of data collection, serious and non-serious 
adverse events, and all protocol violations and deviations. Reports of incomplete data will be reviewed 
by the study team on a regular basis to ensure that data acquisition is complete, accurate, and 
proceeding on schedule. Any evidence of systemic problems in data collection will be resolved quickly. 
 
8.4 
DATA AND SAFETY MONITORING PLAN 
All data and safety issues will be reviewed by all study investigators and study staff at each 
biweekly staff meeting. 
A single Data and Safety Monitor (DSM) will be appointed for this trial. In order to avoid conflicts 
of interest, the DSM will not be a KPNC employee and will not have collaborated directly with any study 
investigators in the past. The DSM will provide written approval of all study procedures and documents 
(including the content of the regular DSM reports and tables) prior to study initiation. It is anticipated that 
formal DSM meetings with the study investigators will occur via teleconference prior to study enrollment 
(to approve all procedures and documents), then at roughly six-month intervals to review all safety and 
data-related information. Changes to the meeting intervals can be made at any time at the DSM's 
discretion. A DSM report will be prepared prior to each meeting; this report will include both blinded and 
unblinded data if requested by the DSM. Adverse-event monitoring and withdrawal of participants are 
discussed above (Sections 7.1 - 7.3). A full Data and Safety Monitoring Plan is contained in a separate 
study document. 
 
 
9.0 
ETHICAL CONSIDERATIONS 
 
9.1 
INFORMED CONSENT 

19 
 
The principles of informed consent described in Food and Drug Administration (FDA) 
regulations (21CFR part 50) will be followed. IRB approval of the protocol and the consent form will be 
given in writing. This protocol and the informed consent document and any subsequent modifications 
will be reviewed and approved by the IRB and the DSM. Written informed consent will be obtained 
from the participant, who will be given ample time to study the document and encouraged to ask 
questions during the telephone consent procedure. The informed consent will describe the purpose of 
the study, the procedures to be followed and the risks and benefits of participation. The participant will 
retain a copy of the consent form, the HIPAA authorization form, and the Research Subject’s Bill of 
Rights. 
 
9.1 
PROCEDURES FOR OBTAINING CONSENT 
If the patient expresses interest in potentially enrolling in the study at their first clinic visit, an 
appointment will be made for a telephone visit with the study Physician's Assistant. At the appointed 
time, the study PA will call the patient at home and present the study details to the patient using an 
IRB-approved script and answer any questions the patient may have. The PA will be sure to 
emphasize that participation is entirely voluntary and that there is no obligation to participate. If the 
patient expresses a desire to enroll in the study, the PA will ask the patient to retrieve the consent and 
HIPAA Authorization forms from the clinic study packet; the PA will then walk through all elements of 
the consent form with the patient, again using an IRB-approved telephone script. If, after this 
procedure, the patient is still interested in enrolling in the study, they will sign their copy of the consent 
form. The same procedure will then be repeated for the HIPAA authorization form. The PA will then 
ask the patient to put both sign forms in the postage-paid reply envelope and mail them back to the 
orthopedics department at the SLN Medical Center. When these forms are received, the PA will then 
sign both forms and enter the consent note on the patient's electronic medical chart. The forms will then 
be set aside in a consistent location for retrieval by the study Project Coordinator or Research 
Assistant. The forms will be scanned into the patient's electronic medical record and the hard copy will 
be stored in a locked file cabinet in a secure area at the Division of Research. If the PA is unavailable, 
any study investigator with a clinical license may conduct the consent procedure. 
 
9.2 
CONFIDENTIALITY 
Data will be collected on paper forms (including the two-week pain and medication diary) and 
entered into a REDCap database. REDCap is a fully HIPAA and 21CFR Part 11 compliant data 
collection application and maintains a high level of security and confidentiality for the study data. Study 
data can only be accessed through a secure password-protected server with access permissions 
limited to study personnel and with nightly redundant backups. All accessing of and changes to the data 
are audited and recorded. Data will be stored on secure servers located behind a firewall at the KPNC 
DOR with nightly redundant backups. All computers used to access the KPNC intranet will follow 
standard access-protection procedures, including regular changing of passwords and formation of an 
audit trail; prior to conduct of the study, all procedures will be tested to ensure that the implemented 
security procedures cannot be circumvented or defeated. All study personnel will undergo required 
HIPAA training (certification of successful completion of HIPAA training is a requirement for 
employment at KPNC). 
The study data collected on paper forms will be stored in locked file cabinets in a secure 
location at the KPNC Division of Research. Only authorized study personnel will have access to the file 
cabinets, which are located in secure sections of the DOR, behind locked doors requiring electronic 
card access. 
Protected Health Information (PHI) will be closely guarded and never shared with individuals 
outside of the research staff, unless compelled to do so by regulation or law. Such data include any 
study-related forms that contain any of the 18 HIPAA identifiers. No PHI will be disclosed in any 
publications or presentations as a result of the work from this study. No PHI will be used in the analysis 
datasets, as it is not necessary (conforming to the “minimum necessary” standard). 
 
 
10.0 
STUDY ADMINISTRATION 

20 
 
10.1 
ORGANIZATIONAL CHART 
The organizational and reporting structure of the project is shown below: 
 
 
Andy Avins, MD, MPH  
 
(DOR PI) 
Adrian Hinman, MD 
(SLN PI) 
 
Stephanie Prausnitz, 
MPH 
(Proj Coordinator) 
 
Cathy Lee, PhD 
 
 
(Biostatistician) 
 
TBN 
(Programmer/Analyst) 
Jack Collins, MBA 
(Research 
Administrator) 
 
Alexander Hoffman, PA 
(Study PA) 
 
Clinic and Operating 
Room Personnel 
 
 
TBN 
(Research Asst) 
 
 
 
 
10.2 CLINICAL SITE: KPNC SAN LEANDRO MEDICAL CENTER 
The Orthopedics Department in the KPNC San Leandro Medical Center is located on the fourth 
floor of the Medical Center at 2500 Merced St. in San Leandro, CA. The Department is a referral center 
for TKA surgery and performs approximately 1300 primary TKAs annually. Twelve TKA surgeons from 
3 Kaiser Permanente hospitals (San Leandro, Oakland, Fremont) perform TKA surgeries in the San 
Leandro Hospital operating rooms. 
The outpatient clinic in San Leandro is physically attached to the hospital and consists of offices 
for 9 full-time orthopedic surgeons, 4 of whom are TKA surgeons. These offices are also shared with 2 
non-operative physicians, 8 physician assistants, 9 medical assistants and one office manager. One 
hundred and fifty to two hundred patients per day are routinely seen for a variety of conditions within 
the scope of orthopedic and sports medicine. Office space is shared with the Podiatry department. All 
orthopedic diagnostic and treatment procedures are included in the scope of practice, including 
appropriate medications and interventional procedures. A close working relationship exists with the 
Department of Radiology. 
 
10.3 
DATA COORDINATING CENTER: KPNC DIVISION OF RESEARCH 
The Data Coordinating Center resides at the Division of Research, Northern California Kaiser 
Permanente in Oakland, California. The data-related activities of the ACCESS trial will be supervised 
by the Dr. Avins (co-PI), Dr. Lee (Biostatistician), and Ms. Prausnitz (Project Manager). The 
Coordinating Center will take responsibility for monitoring recruitment and data quality; regular reports 
of recruitment and issues related to data quality will be produced for monthly project meetings. In 
addition, the Data Coordinating Center will have responsibility for ensuring timely reporting of adverse 
event data, preparation of reports for the DSM, and IRB renewals. As all data collection will be 
centralized at the Division of Research, the Coordinating Center will ensure that all data collection 
forms and systems are working appropriately. 

21 
 
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Sloan M, Premkumar A, Sheth NP. Projected Volume of Primary Total Joint Arthroplasty in the U.S., 2014 to 
2030. J Bone Joint Surg Am. 2018 Sep 5;100(17):1455–60. 
 
2. 
Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in 
the United States from 2005 to 2030. J Bone Joint Surg Am. 2007 Apr;89(4):780–5. 
 
3. 
Bourne RB, Chesworth BM, Davis AM, Mahomed NN, Charron KDJ. Patient satisfaction after total knee 
arthroplasty: who is satisfied and who is not? Clin Orthop. 2010 Jan;468(1):57–63. 
 
4. 
Noble PC, Conditt MA, Cook KF, Mathis KB. The John Insall Award: Patient expectations affect satisfaction 
with total knee arthroplasty. Clin Orthop. 2006 Nov;452:35–43. 
 
5. 
Kelly MP, Prentice HA, Wang W, Fasig BH, Sheth DS, Paxton EW. Reasons for Ninety-Day Emergency 
Visits and Readmissions After Elective Total Joint Arthroplasty: Results From a US Integrated Healthcare 
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6. 
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7. 
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anaesthesia can replace patient-controlled analgesia after total knee arthroplasty: a randomised controlled 
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8. 
Wheeler M, Oderda GM, Ashburn MA, Lipman AG. Adverse events associated with postoperative opioid 
analgesia: a systematic review. J Pain Off J Am Pain Soc. 2002 Jun;3(3):159–80. 
 
9. 
Sharma S, Iorio R, Specht LM, Davies-Lepie S, Healy WL. Complications of femoral nerve block for total 
knee arthroplasty. Clin Orthop. 2010 Jan;468(1):135–40. 
 
10. 
Kandasami M, Kinninmonth AW, Sarungi M, Baines J, Scott NB. Femoral nerve block for total knee 
replacement - a word of caution. The Knee. 2009 Mar;16(2):98–100. 
 
11. 
Manickam B, Perlas A, Duggan E, Brull R, Chan VWS, Ramlogan R. Feasibility and efficacy of ultrasound- 
guided block of the saphenous nerve in the adductor canal. Reg Anesth Pain Med. 2009 Dec;34(6):578–80. 
 
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24 
 
APPENDIX 1: SCHEDULE OF EVALUATIONS 
 
 
VISIT: 
PROCEDURE: 
Initial 
clinic visit 
Telephone 
consent 
call* 
Preop 
call 
Day of 
surgery 
Daily 
patient 
diary 
2-day 
postop 
call 
2-week 
postop 
call* 
3-month 
EMR data 
extraction 
Introduction to study 
X 
X 
Provision of information packet 
X 
Eligibility screening 
X 
X 
Informed consent 
X 
Randomization 
X 
DATA COLLECTED 
Demographics 
X 
Clinical history 
X 
Numerical rating pain scale 
X 
X 
X 
X 
PROMIS-10 
X 
X 
KOOS Jr 
X 
X 
Analgesic use assessment 
X 
Daily pain/medication diary 
X 
Adverse Event Assessment 
X 
X 
X 
 
 
Key: 
EMR = Electronic Medical Record 
Postop = Postoperative 
Preop = Preoperative 
 
*Several items (Demographics, Clinical History, Numerical rating pain scale, PROMIS-10, KOOS Jr, 
Analgesic use assessment) will be collected by the participant at home on a paper 
questionnaire and mailed to the DOR; participants will be reminded to do so during the 
Telephone consent call and at the 2-week closeout postop call. 

25 
 
APPENDIX 2: KEY PERSONNEL 
 
Adrian Hinman, MD 
Co-Principal Investigator 
Orthopedics 
KPNC San Leandro Medical Center 
2500 Merced St 
4th Floor 
San Leandro, CA 94577 
Phone: (510) 454-7292 
E-mail: Adrian.D.Hinman@kp.org 
 
Andrew L. Avins, MD, MPH 
Co-Principal Investigator 
Research Scientist 
KPNC Division of Research 
2000 Broadway 
Oakland, CA 94612 
Phone: (510) 891-3557 
Fax: (510) 891-3606 
E-mail: andy.l.avins@kp.org 
 
Kasey Cortese, MD 
Co-Investigator 
Chief, Orthopedics 
KPNC San Leandro Medical Center 
2500 Merced St 
4th Floor 
San Leandro, CA 94577 
Phone: (510) 454-7295 
E-mail: Kasey.D.Cortese@kp.org 
 
Bejoy Thomas, MD 
Co-Investigator 
Anesthesia 
KPNC San Leandro Medical Center 
2500 Merced St 
San Leandro, CA 94577 
Phone: (510) 913-4859 
E-mail: Bejoy.G.Thomas@kp.org 
 
Catherine Lee, PhD 
Biostatistician 
Kaiser Permanente Division of Research 
2000 Broadway 
Oakland, CA 94612 -2304 
Phone: (510) 891-3556 
Fax: (510) 891-3606 
E-mail: catherine.lee@kp.org 
 
Stephanie Prausnitz, MS 
Project Manager 
KPNC Division of Research 
2000 Broadway 

26 
 
Oakland, CA 94612 -2304 
Phone: (510) 891-3601 
Fax: (510) 891-3606 
E-mail: Stephanie.R.Prausnitz@kp.org 
 
Alexander Hoffman, PA-C 
Orthopedics 
KPNC San Leandro Medical Center 
2500 Merced St 
4th Floor 
San Leandro, CA 94577 
Phone: (510) 454-7317 
E-mail: alexander.e.hoffman@kp.org