Clinical trial NCT04005859
Conditions: Colorectal Disorders
Sponsor: Wake Forest University Health Sciences
Start date: 2018-02-22; Completion date: 2021-07-20
Enrollment: 61 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To compare the analgesic impact of intravenous perioperative lidocaine infusion with preoperative liposomal bupivacaine TAP block in colorectal surgery. This is to be integrated into the standard ERAS protocol currently utilized at Carolinas Medical Center. Primary endpoints will be postoperative pain as measured by verbal rate scale (VRS), postoperative morphine equivalents utilized per day, and over 30 days. Secondary endpoints will include date of ambulation, return of bowel function (first flatus), tolerance of goal diet, incidence of post-operative nausea and vomiting during hospital stay, length of stay (hospital and PACU), post-operative morbidity (Clavien-Dindo, related to both anesthesia and surgery), cost of hospitalization (operative, PACU, postoperative stay, and total) and quality of life on follow up.

Detailed description:

Arms: arm 1: CONTROL: Intravenous lidocaine, pre- and post-surgery (IV Lido) arm 2: EXPERIMENTAL: TAP block with liposomal bupivacaine will be given as an injection (Exparel)
Interventions: intervention 1: Exparel intervention 2: IV Lidocaine
Intervention descriptions: intervention 1: 2\. Liposomal bupivacaine TAP block (experimental arm)

1. Block will be administered after induction of anesthesia and before incision by a specifically trained attending surgeon or surgical fellow with the colorectal service.
2. A single vial of liposomal bupivacaine (20 mL 1.3%, 13.3mg/mL, 266 mg) will be diluted in 50cc bupivacaine to a volume of 60cc prior to administration. This will be divided into 2 doses for bilateral TAP blocks.
3. The LB will be administered under ultrasound guidance in the transversus abdominis plain per manufacturer recommendations.
4. Adhesive tapes will be applied at the level of the TAP block puncture sites. intervention 2: 1\. Intravenous Lidocaine infusion (control arm, current standard of care)

1. 100 mg/5mL intravenous bolus of lidocaine 2% PF 5mL will be initiated by anesthesia service prior to general anesthesia induction.
2. 1.5 mg/kg/hr to begin prior to incision and continue until discontinued 1 hr postoperatively in PACU. Patients will be monitored in PACU for at least 30 minutes after discontinuation of lidocaine drip.
3. Adhesive tapes will be applied at the presumed level of TAP block puncture sites.

Protocol documents:
Prot_SAP_001.pdf: 
Page 1 of 11 
COVER PAGE: 
Title: Pain control in colorectal surgery: liposomal bupivacaine block versus intravenous 
lidocaine 
NCT: NCT04005859 
Date of Protocol: 02/07/2018 
 
 


Page 2 of 11 
 
Title of Protocol: 
Pain control in colorectal surgery: liposomal bupivacaine block versus 
intravenous lidocaine 
 
Principal Investigator: Kevin Kasten, MD 
 
Sub-Investigators: 
Bradley R. Davis, MD, Angela Kao, MD, Kathryn Schlosser, MD, 
Michael R. Arnold, MD, Javier Otero, MD, & B. Todd Heniford, MD 
 
Carolinas Hernia Center 
Division of GI and Minimally Invasive Surgery 
1025 Morehead Medical Center Drive, Charlotte, NC 28204 
Angela.Kao@carolinashealthcare.org 
Office: 704-355-3168 
Fax: 704-355-4117 
 
Background and Significance: 
Enhanced Recovery After Surgery (ERAS) pathways are intended to reduce physiologic 
stress of surgery and minimize organ dysfunction. ERAS pathways often include multi-modal 
patient education, early diet advancement, early ambulation, and non-narcotic analgesia with 
goals of earlier return of bowel function, activity, and discharge from hospital. While first 
developed for colorectal surgery, the principles of ERAS pathways have been applied to 
bariatric, urologic, gynecologic oncology, gastric, and pancreatic postsurgical pathways with 
good success.1–5 Effective postoperative pain control is essential to a successful ERAS pathway, 
as a patient with improved pain control has early oral intake, improved mobility, and potentially 
earlier discharge from hospital. Opiates are often included in postsurgical pain regimens, though 
the negative impact of patient sedation, nausea, and decreased gastric motility can impede the 
target outcomes of an ERAS pathway. Reducing narcotic use has been demonstrated to improve 
patient recovery and decrease length of stay.  
In the interest of decreasing narcotic use and improving postsurgical outcomes, multiple 
non-narcotic analgesic interventions have been developed and implemented as integral to ERAS 
protocols. Preoperative administration of sodium channel blockers such as lidocaine and 
bupivacaine as a local anesthetic at the surgical incision, or as a transversus abdominis plane 
(TAP) regional nerve block, can improve postoperative pain.6,7 Multiple studies have 
demonstrated that intravenous lidocaine decreases postoperative pain and facilitates faster 
restoration of bowel function in colorectal surgery8–11 and its use has become commonplace at 
this institution as an adjunct to the current ERAS protocol. The use of intravenous lidocaine to 
assist in perioperative pain control is used routinely during colorectal operations at this 
institution. A recent meta-analysis identified fourteen randomized, controlled trials in which 
intravenous lidocaine was administered as an adjunct to perioperative pain control, providing a 
reduction in opiate pain use and pain scores after laparoscopic surgery with no adverse events 
associated with administration of lidocaine. This is in concordance with the timing and dosage of 
multiple previous studies which have safely administered this medication perioperatively, and 
demonstrated improved postoperative pain control.7–13 While utilization of both TAP blocks and 
IV lidocaine has been shown to improve postoperative pain control, the efficacy of these 


Page 3 of 11 
interventions is limited by the half-life of the sodium channel blocker used, with most patients 
benefiting primarily on the day of surgery.13 
In response to the need for improved, long-lasting non-narcotic pain control, an extended 
release liposomal bupivacaine (LB) was developed for use in surgical intervention. This product 
suspends bupivacaine in lipid-based particle layers which are slowly absorbed by the body, 
releasing bupivacaine over 96 hours. The FDA has approved LB for use in hemorrhoidectomy, 
bunionectomy, TAP block, mammoplasty, total knee arthroplasty, and inguinal hernia repairs. 
Since development, the use of locally injected LB has been studied as a local injection, as a 
nerve block, and as a TAP block. The FDA has approved the administration of liposomal 
bupivacaine as a TAP block, which is considered a regional anesthetic.14,15 As a local injection, it 
has been shown to improve postsurgical pain control in augmentation mammoplasty when 
compared to bupivacaine.16 It has been utilized as a brachial plexus block in patients having 
shoulder surgery, with improved pain control over bupivacaine.17 Patients undergoing 
hysterectomy had significantly decreased pain scores and opioid use after LB TAP block when 
compared with bupivacaine TAP block,18 and patients undergoing open colectomy had decreased 
length of stay and opioid use when compared to placebo.19 
To date, there are currently no studies directly comparing systemic IV lidocaine infusion 
with LB TAP block. While both have been independently demonstrated to provide improved 
pain control over placebo, as well as improved pain control over other local anesthesias as 
described above,6,8–12,16–21 it is unclear which may provide better analgesia for colorectal surgical 
intervention. Currently, intravenous lidocaine is regularly used for assistance in pain control 
during colorectal surgery at this institution. This administered at the discretion of the attending 
surgeon. We hypothesize that administration of LB as a TAP block will provide longer-term and 
thus improved postoperative analgesia to patients undergoing minimally invasive colorectal 
intervention, with resulting decreased narcotic use, earlier ambulation, and earlier return of 
bowel function.  
 
Purpose of Study: 
To compare the analgesic impact of intravenous perioperative lidocaine infusion with 
preoperative liposomal bupivacaine TAP block. This is to be integrated into the standard ERAS 
protocol currently utilized at Carolinas Medical Center. Primary endpoints will be postoperative 
pain as measured by verbal rate scale (VRS), postoperative morphine equivalents utilized per 
day, and over 30 days. Secondary endpoints will include date of ambulation, return of bowel 
function (first flatus), tolerance of goal diet, incidence of post-operative nausea and vomiting 
during hospital stay, length of stay (hospital and PACU), post-operative morbidity (Clavien-
Dindo, related to both anesthesia and surgery), cost of hospitalization (operative, PACU, 
postoperative stay, and total) and quality of life on follow up. 
 
Study Design: 
 
Enrollment of Subjects: 
Patients will be prospectively enrolled from Carolinas Medical Center Colorectal Surgery 
Outpatient Clinic and the Levine Cancer Institute Surgical Oncology Outpatient Clinic. Specific, 
IRB-approved consent will be obtained for enrollment in the study and for inclusion in the 
surgical outcomes database. 


Page 4 of 11 
We will include patients 18 to 70 undergoing elective laparoscopic colon resection for 
benign or malignant disease. We will include laparoscopic, robotic assisted laparoscopic, and/or 
hand assisted cases. Cases converted to open will be included for intention to treat analysis. 
Creation of ostomy will not preclude enrollment. 
Patients who have a history of chronic pain on chronic opioids, currently on suboxone or 
methadone, or with a contraindication to lidocaine administration will be excluded. Planned open 
interventions as well as planned concurrent non-colorectal interventions will be excluded. 
Patients who are under 18 or over 70, have liver or renal dysfunction, epilepsy, psychomotor 
retardation, BMI >40, sleep apnea, or cardiac rhythm disorders, or are pregnant will be excluded 
(image 1). 
Patients who have complications of Clavien-Dindo class 3 or greater will be included in 
calculations of complication rates. However, they will not be included in calculations of 
postoperative morphine equivalents, as repeat intervention will confound the normal course of 
postoperative pain control. 
 
Data Collection: 
Research fellows, data analysts, and clinical research team will be responsible for 
tracking subject enrollment and compliance with protocol. Patient outcomes and quality of life 
will be entered under a deidentified patient key in the surgical outcomes database which is 
prospectively maintained. 
The patient key containing PHI will be stored in a password accessed digital file on a 
limited access folder on a secure network. Access to this folder is only available to primary 
investigators and associated staff. Password access to this file will be granted only to sub-
investigators. Computer access to this network is in an office space limited to employees during 
the working hours and requires fob access granted by security during after-hours.  
Data of interest will be recorded on a deidentified spreadsheet with no linking patient 
information.  The spreadsheet will be kept on a limited access folder on a secure network. 
Following data collection period, all variables and data will be deidentified including during any 
subsequent data analysis or publication.  
 
Research Design: 
Creation of study arms: 
We plan to conduct a single-center, prospective, randomized, blinded study comparing 
the analgesic impact of perioperative IV lidocaine infusion with post-induction, pre-incision LB 
TAP block. Patients will be randomized to one of two study arms using a computer-generated 
list. Allocation concealment will be ensured by enclosing assignments in sealed, opaque, 
sequentially numbered envelopes will be opened upon arrival of the patient in the operating 
room. Postoperative outcomes will be assessed by personnel who remain blinded to the type of 
intervention throughout the study.  
Groups will receive administration of analgesia as follows: 
1. Intravenous Lidocaine infusion (control arm, current standard of care) n= 35 
a. 100 mg/5mL intravenous bolus of lidocaine 2% PF 5mL will be initiated by 
anesthesia service prior to general anesthesia induction. 
b. 1.5 mg/kg/hr to begin prior to incision and continue until discontinued 1 hr 
postoperatively in PACU. Patients will be monitored in PACU for at least 30 
minutes after discontinuation of lidocaine drip. 


Page 5 of 11 
c. Adhesive tapes will be applied at the presumed level of TAP block puncture 
sites. 
2. Liposomal bupivacaine TAP block (experimental arm) n= 35 
a. Block will be administered after induction of anesthesia and before incision 
by a specifically trained attending surgeon or surgical fellow with the 
colorectal service. 
b. A single vial of liposomal bupivacaine (20 mL 1.3%, 13.3mg/mL, 266 mg) 
will be diluted in 50cc bupivacaine to a volume of 60cc prior to 
administration. This will be divided into 2 doses for bilateral TAP blocks. 
c. The LB will be administered under ultrasound guidance in the transversus 
abdominis plain per manufacturer recommendations. 
d. Adhesive tapes will be applied at the level of the TAP block puncture sites. 
 
Perioperative care (ERAS): 
All patients involved in this study will be enrolled in the current CMC ERAS protocol, 
which is current standard of care at this institution. This protocol includes: 
• Nutritional supplements 1 week before surgery 
• Clear liquids up to 2 hours before surgery 
• Early postoperative ambulation 
• Clear liquid diet available immediately postoperatively 
• Standard postoperative pain control per ERAS protocol with scheduled acetaminophen, 
gabapentin, and opiates available per request. 
• Early Foley catheter removal (POD1 unless otherwise specified) and encouragement of 
ambulation per current ERAS protocol. 
 
Evaluation of primary outcomes: 
Patients will report pain by the verbal pain scale (VRS) every 6 hours postoperatively for 
the first 24 hours, then at least every 6 hours as per standard nursing protocol with vital signs and 
administration of pain medications. This verbal pain scale is currently recorded by nursing staff 
with every pain medication administered as part of standard protocol. It is available in the 
medical record with every pain medication administered, as well as with vital sign checks. After 
discharge, pain/VRS scores will be measured at 2 and 4 weeks postoperatively by patient survey. 
Any patient requesting more analgesia at any time will be assessed and provided with additional 
oral or intravenous administration of analgesia as per ERAS protocol, with goal of pain control 
to a level under 40mm VAS measurement. Standard postoperative analgesia includes but is not 
limited to scheduled acetaminophen, gabapentin, and opiates available per request. 
Total opioid analgesia administered postoperatively will be recorded as morphine 
equivalents and stratified per postoperative day, per hospitalization and at 2 and 4 weeks 
postoperatively. In hospital, PCA and PRN opioids will be reviewed and recorded daily. This 
information is available in the patient medical record, as all analgesic medications are recorded 
at distribution by nursing staff. After discharge, patients will bring opioid prescription bottles to 
follow up appointments for accurate recording of usage, in addition to self-reported opioid 
dosing. 
 
Evaluation of secondary outcomes: 


Page 6 of 11 
Secondary outcomes will be recorded and evaluated, including date of ambulation, return 
of bowel function (first flatus), tolerance of goal diet, incidence of post-operative nausea and 
vomiting during hospital stay, length of stay (hospital and PACU), post-operative morbidity 
(Clavien-Dindo, related to both anesthesia and surgery), cost of hospitalization (operative, 
PACU, postoperative stay, and total) and quality of life on follow up. 
 
Evaluation of adverse outcomes: 
Postoperative outcomes will be recorded and categorized per Clavien-Dindo 
classification of surgical outcomes. Outcomes of grade III or greater will be considered major 
complications, and these patients will be removed from further evaluation of pain control. These 
complications will be included in total outcomes. 
 
Endpoint 
Intravenous lidocaine or TAP Block will be used as a perioperative adjunct, then at the 
conclusion of the study chart review will be performed to evaluate if either intervention provided 
superior pain control as demonstrated by narcotic need, VAS pain scale values, return of bowel 
function, time to diet, or length of stay (LOS). 
 
 


Page 7 of 11 
Image 1: Trial study design 
 
 
Power and Sample Size: 
Based on differences detected in prior studies, a power analysis was performed using 
postoperative pain and length of stay as the primary outcome variables. We will need 20 patients 
per group to show a clinically significant reduction in pain and total morphine equivalents with 
80% power and type I error rate of 5%. Anticipating study withdrawals (3-5 per group), and 
complications requiring further intervention (3-5 per group), we will enroll 35 patients per group, 
70 patients in total.  
 
Data Analysis: 
Data will be analyzed using standard statistical methods utilizing the SAS program 
version 9.3 (SAS, Cary, NC, USA). Descriptive statistics including means and standard 
deviations, or counts and percentages, will be used to describe the study population on all 


Page 8 of 11 
variables. Patients will be grouped based on study arm. Demographic and baseline measures will 
be compared for differences between groups. For continuous variables, comparisons will be 
made between groups using t-tests and Wilcoxon-Mann-Whitney tests. For categorical variables, 
Chi-square and Fisher’s exact tests will be used to make comparisons between groups. For the 
primary analysis, morphine equivalents, pain scores, weight (kg), length of operation (min.), 
estimated blood loss (cc), total cost ($), and length of postoperative stay (days) will be compared 
between groups using the same tests as outlined above; additional analyses will compare 
prevalence of peri-operative complications between groups. Multivariate regression will be used 
to control for potential confounding variables such as age, gender, or others as identified. The 
level of significance will be set at p <0.05 for all comparisons. 
 
Risks and Benefits: 
Both analgesic interventions (IV lidocaine and LB TAP block) have been demonstrated 
to be superior to opioid-only analgesia for postoperative pain control in multiple studies. IV 
lidocaine is routinely used for augmentation of perioperative pain control in colorectal and other 
surgical procedures at this institution.7–13 The administration of a long acting LB has the 
potential to improve pain control for a longer period postoperatively.6,16–19 Improved 
postoperative pain control can improve patient outcomes on multiple levels, including earlier 
diet, earlier ambulation, and earlier return of bowel function. 
Adverse outcomes to administration of liposomal bupivacaine include the potential cardiac 
side effects of administration of sodium channel blockers such as lidocaine and bupivacaine. The 
side effects of these medications are directly related to the serum level. For lidocaine, side effects 
are rare at serum levels within the 2-6 mcg/mL range. Side effects are more pronounced in 
patients with liver dysfunction, pulmonary diseases where the predominant problem is carbon 
dioxide retention, and congestive heart failure, who are therefore excluded from this study. We 
will comply with manufacturer and FDA warnings regarding the maximum dosage of 
bupivacaine and/or lidocaine.14,22,23 Multiple precautions via pharmacy, anesthesia, and OR staff 
will be taken to prevent administration of both drugs to a single patient. Other adverse events 
include accessing confidential PHI, which we hope to prevent using the data security plan 
detailed previously. 
 
Safety Monitoring: 
The safety monitor will provide a professional opinion and review of any adverse events 
potentially related to the intervention. The co-investigators and research staff will regularly 
review and document the operative and postoperative course of patients enrolled in the study. 
The patient will be seen daily by the surgical team monitoring their care and wellbeing. The 
patient will also be seen or reviewed daily by an attending surgeon or resident involved in the 
study while they are in hospital. The Co-investigators will document adverse events as follows: 
1. Any adverse events potentially related to the intervention (IV lidocaine or liposomal 
bupivacaine TAP block) will be reported to the safety monitor, the primary 
investigator, and the IRB within 48 hours of discovery.  
Events potentially associated with the intervention include but are not limited to: 
a. Allergic reaction to administered medication as demonstrated by rash, puritis, 
airway compromise, or hives. 
b. Withdrawal from the study due to adverse reaction to medication. 


Page 9 of 11 
c. Events potentially associated with lidocaine or bupivacaine toxicity as listed 
in the consent form and the FDA labels.14,23,24 
i. Not severe: perioral numbness 
ii. Mild to Moderate: severe dizziness, decreased hearing, tremors, 
changes in blood pressure and heart rate 
iii. Severe: drowsiness, confusion, muscle twitching, convulsions, loss of 
consciousness, cardiac arrhythmias, and cardiac arrest 
d. Events associated with injection of liposomal bupivacaine into the abdominal 
wall for the TAP Block as listed in the consent form.  
i. Abdominal wall swelling or bleeding in excess of appropriate post-
surgical changes 
ii. Abdominal wall bleeding requiring transfusion or intervention 
2. All adverse events not potentially related to the intervention will be recorded and 
reviewed per Clavien-Dindo complication classifications. A list of adverse events will 
be emailed to the primary investigator and the safety monitor every 6 months for 
review. Upon review by the primary investigator and safety monitor, any adverse 
events potentially associated with the interventions performed (as listed above) will 
be submitted to the IRB within 48 hours of discovery. 
3. Any patient who is withdrawn from the study for any reason will be reported to the 
primary investigator and safety monitor every six months for review. Reasons for 
withdrawal include but are not limited to patient preference, physician judgment, 
anesthesiologist judgment, adverse event not related to intervention, adverse event 
related to intervention. 
4. The study will be stopped if 
a. Either intervention is deemed unsafe by the safety monitor, the primary 
investigator, or the IRB committee. 
b. An intervention is deemed significantly superior, rendering further utilization 
of the alternate intervention unethical.  
 
References 
1.  
Dogan K, Kraaij L, Aarts EO, et al. Fast-track bariatric surgery improves perioperative 
care and logistics compared to conventional care. Obes Surg. 2015;25(1):28-35. 
doi:10.1007/s11695-014-1355-2. 
2.  
Daneshmand S, Ahmadi H, Schuckman AK, et al. Enhanced Recovery Protocol after 
Radical Cystectomy for Bladder Cancer. J Urol. 2014;192(1):50-56. 
doi:10.1016/j.juro.2014.01.097. 
3.  
Nelson G, Kalogera E, Dowdy SC. Enhanced recovery pathways in gynecologic 
oncology. Gynecol Oncol. 2014;135(3):586-594. doi:10.1016/j.ygyno.2014.10.006. 
4.  
Grantcharov TP, Kehlet H. Laparoscopic gastric surgery in an enhanced recovery 
programme. Br J Surg. 2010;97(10):1547-1551. doi:10.1002/bjs.7184. 
5.  
Coolsen MME, van Dam RM, Chigharoe A, Olde Damink SWM, Dejong CHC. 
Improving outcome after pancreaticoduodenectomy: experiences with implementing an 
enhanced recovery after surgery (ERAS) program. Dig Surg. 2014;31(3):177-184. 
doi:10.1159/000363583. 
6.  
Kim AJ, Yong RJ, Urman RD. The Role of Transversus Abdominis Plane Blocks in 
Enhanced Recovery After Surgery Pathways for Open and Laparoscopic Colorectal 


Page 10 of 11 
Surgery. J Laparoendosc Adv Surg Tech A. 2017;27(9):909-914. 
doi:10.1089/lap.2017.0337. 
7.  
Helander EM, Webb MP, Bias M, Whang EE, Kaye AD, Urman RD. A Comparison of 
Multimodal Analgesic Approaches in Institutional Enhanced Recovery After Surgery 
Protocols for Colorectal Surgery: Pharmacological Agents. J Laparoendosc Adv Surg 
Tech. 2017;27(9):903-908. doi:10.1089/lap.2017.0338. 
8.  
Groudine SB, Fisher HA, Kaufman RP, et al. Intravenous lidocaine speeds the return of 
bowel function, decreases postoperative pain, and shortens hospital stay in patients 
undergoing radical retropubic prostatectomy. Anesth Analg. 1998;86(2):235-239. 
http://www.ncbi.nlm.nih.gov/pubmed/9459225. Accessed February 7, 2018. 
9.  
Tikuišis R, Miliauskas P, Samalavičius NE, Žurauskas A, Samalavičius R, Zabulis V. 
Intravenous lidocaine for post-operative pain relief after hand-assisted laparoscopic colon 
surgery: a randomized, placebo-controlled clinical trial. Tech Coloproctol. 
2014;18(4):373-380. doi:10.1007/s10151-013-1065-0. 
10.  
Swenson BR, Gottschalk A, Wells LT, et al. Intravenous Lidocaine Is as Effective as 
Epidural Bupivacaine in Reducing Ileus Duration, Hospital Stay, and Pain After Open 
Colon Resection. Reg Anesth Pain Med. 2010;35(4):370-376. 
doi:10.1097/AAP.0b013e3181e8d5da. 
11.  
Herroeder S, Pecher S, Schönherr ME, et al. Systemic lidocaine shortens length of 
hospital stay after colorectal surgery: a double-blinded, randomized, placebo-controlled 
trial. Ann Surg. 2007;246(2):192-200. doi:10.1097/SLA.0b013e31805dac11. 
12.  
Ventham NT, Kennedy ED, Brady RR, et al. Efficacy of Intravenous Lidocaine for 
Postoperative Analgesia Following Laparoscopic Surgery: A Meta-Analysis. World J 
Surg. 2015;39(9):2220-2234. doi:10.1007/s00268-015-3105-6. 
13.  
Staikou C, Avramidou A, Ayiomamitis GD, Vrakas S, Argyra E. Effects of Intravenous 
Versus Epidural Lidocaine Infusion on Pain Intensity and Bowel Function After Major 
Large Bowel Surgery: a Double-Blind Randomized Controlled Trial. J Gastrointest Surg. 
2014;18(12):2155-2162. doi:10.1007/s11605-014-2659-1. 
14.  
HIGHLIGHTS OF PRESCRIBING INFORMATION.; 2015. 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022496s019lbl.pdf. Accessed 
February 8, 2018. 
15.  
Perry BK, Manager R. Supplement Approval: Exparel (Bupivacaine Liposome) Injectable 
Suspension.; 2015. 
https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2015/022496Orig1s019ltr.pdf. 
Accessed February 8, 2018. 
16.  
Nadeau MH, Saraswat A, Vasko A, Elliott JO, Vasko SD. Bupivacaine Versus Liposomal 
Bupivacaine for Postoperative Pain Control after Augmentation Mammaplasty: A 
Prospective, Randomized, Double-Blind Trial. Aesthetic Surg J. 2016;36(2):NP47-52. 
doi:10.1093/asj/sjv149. 
17.  
Vandepitte C, Kuroda M, Witvrouw R, et al. Addition of Liposome Bupivacaine to 
Bupivacaine HCl Versus Bupivacaine HCl Alone for Interscalene Brachial Plexus Block 
in Patients Having Major Shoulder Surgery. Reg Anesth Pain Med. 2017;42(3):334-341. 
doi:10.1097/AAP.0000000000000560. 
18.  
Gasanova I, Alexander J, Ogunnaike B, et al. Transversus Abdominis Plane Block Versus 
Surgical Site Infiltration for Pain Management After Open Total Abdominal 
Hysterectomy. Anesth Analg. 2015;121(5):1383-1388. 


Page 11 of 11 
doi:10.1213/ANE.0000000000000909. 
19.  
Cohen S. Extended pain relief trial utilizing infiltration of Exparel&amp;reg;, a long-
acting multivesicular liposome formulation of bupivacaine: a Phase IV health economic 
trial in adult patients undergoing open colectomy. J Pain Res. 2012;5:567. 
doi:10.2147/JPR.S38621. 
20.  
Helander EM, Webb MP, Bias M, Whang EE, Kaye AD, Urman RD. A Comparison of 
Multimodal Analgesic Approaches in Institutional Enhanced Recovery After Surgery 
Protocols for Colorectal Surgery: Pharmacological Agents. J Laparoendosc Adv Surg 
Tech A. 2017;27(9):903-908. doi:10.1089/lap.2017.0338. 
21.  
Staikou C, Avramidou A, Ayiomamitis GD, Vrakas S, Argyra E. Effects of intravenous 
versus epidural lidocaine infusion on pain intensity and bowel function after major large 
bowel surgery: a double-blind randomized controlled trial. J Gastrointest Surg. 
2014;18(12):2155-2162. doi:10.1007/s11605-014-2659-1. 
22.  
Fda, Cder. Guidance for Clinical Investigators, Sponsors, and IRBs Investigational New 
Drug Applications (INDs) — Determining Whether Human Research Studies Can Be 
Conducted Without an IND. Fed Regist. 2013. 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default
.htm. Accessed February 8, 2018. 
23.  
fda, cder. Lidocaine Hydrochloride and 5% Dextrose Injection, USP in Plastic Container 
VIAFLEX Plus Container.; 2017. 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018461s058lbl.pdf. Accessed 
February 8, 2018. 
24.  
fda, cder. Lidocaine Hydrochloride and 5% Dextrose Injection USP.; 2013. 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019830s018lbl.pdf. Accessed 
February 8, 2018. 
 
 

ICF_002.pdf: 
Official Title:   Pain Control in Colorectal Surgery: Liposomal Bupivacaine Block Versus 
Intravenous Lidociane 
NCT04005859
Date: 6/6/2018


Carolinas HealthCare System-Department of Surgery / Protocol Number (01-18-16) 
Page 1 of 9 
 
 
Kevin Kasten, MD 
Advarra IRB Approved Version 6 Jun 2018 
 
 
 
 
 
 
CAROLINAS HEALTHCARE SYSTEM 
CONSENT TO PARTICIPATE IN A RESEARCH STUDY 
 
Sponsor / Study Title: 
 
Carolinas HealthCare System-Department of Surgery / Pain 
Control in Colorectal Surgery: Liposomal Bupivacaine block 
versus Intravenous Lidocaine 
 
Protocol Number: 
 
(01-18-16) 
Principal Investigator: 
(Study Doctor) 
 
Kevin Kasten, MD 
 
Telephone: 
 
 
(24 Hours) 
 
Address: 
Carolinas HealthCare System 
Carolinas HealthCare System-Center for Digestive Health 
 
 
 
 
 
Please read this form carefully.  Take time to ask the study doctor or study staff as many questions 
about the study as you would like.  The study doctor or study staff can explain words or information 
that you do not understand.  Reading this form and talking to the study doctor or study staff may 
help you decide whether to take part or not.  If you decide to take part in this study, you must sign 
and date your name at the end of this form.  You cannot take part in this research study until you 
sign and date this form. 
 
INTRODUCTION 
Dr. Kevin Kasten or Dr. Bradley Davis is asking you to participate in the above-named research 
study. This research study is being conducted to see if a different kind of anesthesia can improve the 
recovery of patients who must undergo a laparoscopic colectomy (removal of part or all of your 
colon) at Carolinas HealthCare System (CHS). You are one of 70 patients being asked to participate 
because you have been diagnosed with a colon problem that will require laparoscopic colectomy. 
The purpose of this study is to compare two forms of supplemental pain control used at the time of 
your surgery. Your pain control and recovery after surgery will be evaluated during your hospital stay 
and at scheduled intervals after you leave the hospital. Your participation in this study will last for 6 
months after your surgery. 
 
HOW THE STUDY WORKS 
Currently, most colectomy patients at Carolinas Medical Center (CMC) receive intravenous (IV) 
lidocaine at the time of surgery, followed by IV medicine (for example, morphine, dilaudid) and oral 


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opioid pain medication (for example, oxycodone, hydrocodone) after surgery. Opioid pain 
medications are very good at treating pain, but have some side effects such as nausea and 
constipation. Reducing the amount of opioid medication taken after surgery can reduce the chances 
of experiencing these side effects. IV lidocaine has been shown to reduce patients’ pain and reduce 
the amount of opioid medications needed after surgery. IV lidocaine is what we currently use to help 
with pain control. Injections of liposomal bupivacaine (a long-acting relative of lidocaine) in the 
abdominal muscles (TAP block) before surgery have also been shown to reduce patients’ pain and 
decrease opioid use. Because both treatments have been shown to reduce pain and the need for 
opioid medications after surgery, we plan to research which treatment is better. 
If you agree to be in the study, you would be randomized to one of the two study treatment 
methods. Being randomized means that you are put in a group by a chance process, like flipping a 
coin. Your chance of receiving one of the study treatments is one in two (fifty-fifty chance). You 
won't know what group you are placed in. Although you will not know which study treatment you 
are receiving, this information can be determined in the event of an emergency. 
There are two arms (study treatment groups) in this study. You will either receive intravenous 
lidocaine, or a TAP block of liposomal bupivacaine at the time of surgery. After surgery, you will 
receive standard pain medications, including intravenous and oral opioids, to treat your pain.  
•
Subject receiving IV lidocaine will receive IV lidocaine in the operating room, and for one
hour after in the recovery room (PACU)
•
Subjects receiving a TAP block with liposomal bupivacaine will receive the injections in the
operating room, after they are unconscious (under anesthesia) and before the operation
starts.
After the operation, all subjects will have band-aids on their abdomen so they cannot tell whether 
they had the TAP block, or the IV lidocaine. 
We do not expect that either study treatment, IV lidocaine or TAP block, will completely control 
your pain. We expect you to need some opioids for pain control after surgery. You will still receive 
pain control as needed. We plan to compare how much additional medication you will need, to 
measure the effectiveness of each study treatment group. 
After surgery, we will ask you about your pain at least every six hours for the first few days. We will 
record how much additional medication is required to treat your pain. We will also record signs that 
you are feeling better, such as moving around, eating, and passing gas (farting).  
Once you leave the hospital we will ask to see you at two weeks and four weeks after surgery. We 
will ask you to bring your pain pills with you so we can see how much medication you needed. If 
you do not have an appointment near two or four weeks after surgery, we will call you and ask about 
your pain and remaining pills over the phone. 


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The study of IV lidocaine and liposomal bupivacaine TAP blocks is a subset of an Enhanced 
Recovery After Surgery (ERAS) program. ERAS is a program we have initiated to help people 
recover from surgery more quickly. It includes using many forms of non-opioid pain control, 
encouraging walking, and allowing patients to eat early after surgery. ERAS has been used with great 
success in colorectal surgery, allowing patients to feel better and go home sooner.  
 
RISKS 
The study poses minimal risk above and beyond the risks of the surgery itself. It involves 
comparison of two effective pain medications which are approved by the FDA. We expect that you 
will need additional medications to help control your pain after surgery. Regardless of your 
participation in this study we will regularly check and treat your pain after surgery until it is well 
controlled.  
 
As with all medications, side effects may include allergic reaction. Allergic reactions may range from 
minor itching or rash to major reactions which can result in death. 
 
Likely: 
• Side effects of narcotic pain medication include itching, nausea, vomiting, constipation, 
drowsiness. 
• One study treatment may be better than the other at treating pain. We will not know if one 
arm is superior to the other until after we perform this study. 
• Subjects who receive the liposomal bupivacaine TAP block may feel additional soreness at 
the sites of injection. We believe that the pain relief from the medication will counter this. 
 
Less likely: 
• The most common adverse reactions following excessive administration of IV Lidocaine are:  
o Perioral (around the mouth) numbness 
o Nausea and vomiting  
It is rare to have side effects of serum lidocaine levels between 2-6 mcg/mL. We are careful 
not to exceed this amount. 
• The same complications are rare but possible for overdosing of liposomal bupivacaine. 
• Injection of liposomal bupivacaine into the abdominal muscles for a TAP block can cause 
bleeding or swelling in the abdominal wall. 
 
Rare but serious 
• Mild to moderate side effects of intravenous lidocaine (at serum levels 8‐12 mcg/mL) 
include:  
o Nausea and vomiting 
o Severe dizziness 


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Kevin Kasten, MD 
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o Decreased hearing 
o Tremors 
o Changes in blood pressure and pulse. 
Nausea and vomiting without other lidocaine side effects in the postoperative setting is 
unlikely to be related to the lidocaine. 
 
• Severe side effects intravenous lidocaine (at serum levels greater than 12 mcg/mL) includes: 
o Drowsiness 
o Confusion 
o Muscle twitching 
o Convulsions 
o Loss of consciousness 
o Cardiac arrhythmias (abnormal heart rhythms)  
o Cardiac arrest 
• The same complications are rare but possible for overdosing of liposomal bupivacaine. 
 
If you have problems that may be related to your study treatment, your study doctor may “break the 
code” to find out which group you are in. You would then no longer be in the study, and your 
postoperative care would continue as standard of care. 
 
An additional risk to you is the release of information from your health records. The study doctors 
and the study site will protect your records so that your name, address, and phone number will be 
kept private. Nevertheless, there is still a small risk associated with this to your confidentiality. 
 
The study poses minimal risk to subjects. Data collection from past medical records depends upon 
subject identifiers for data collection. HIPAA compliance in clinical and pathologic data handling 
will ensure protection of subjects’ rights to privacy. Data access will be restricted to those involved 
in data collection or analysis. 
 
INCLUSION/EXCLUSION CRITERIA 
• Elective laparoscopic colectomy patients aged between 18 and 75 will be entered in the 
protocol. 
• Exclusion: These patients will not be included in the study. If you have one or more of these 
problems, please notify your study doctor. 
o Allergy to lidocaine or similar medication 
o Chronic pain with daily opioid use before surgery 


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o Liver dysfunction 
o Renal (kidney) insufficiency 
o Epilepsy 
o BMI greater than 40 
o Sleep apnea 
o Cardiac rhythm disorders 
o Planned open procedures, or planned procedures other than colectomy  
 
BENEFITS 
This study may or may not improve your condition. The information gained from your case may 
benefit others with your condition. However, we believe the protocol may allow subjects to feel 
better faster, return to their daily activities faster, and return home from the hospital more quickly. 
 
ALTERNATIVE PROCEDURE/TREATMENT 
If you choose not to participate in this study, your colectomy will be performed to the current 
standards of care. You will not receive additional treatments that are not standard of care. You 
should talk with your study doctor about your options and their risks and benefits. 
 
ADDITIONAL COST 
Participating in this study should not increase your out of pocket expenses. There may be charges 
you are responsible for, such as a nutritional supplement and other liquids related to ERAS. Any 
additional charges will not be covered by Carolinas HealthCare System.  
 
COMPENSATION 
In the event that you are harmed as a result of your participation in this study, we will provide or 
arrange for treatment as necessary.  This treatment, as well as other medical expenses, will be billed 
to you or your insurance company in the usual manner. In no way does signing this consent form 
waive your legal rights nor does it relieve the investigators, Sponsor or involved institutions from 
their legal and professional responsibilities. 
 
If you become ill or are hurt while you are in the study, get the medical care that you need right 
away. 
 
YOUR PAYMENT FOR BEING IN THE STUDY 
You will not be paid for being in this study. 
 
WITHDRAWAL 
Your participation in this study is completely voluntary. You should feel under no pressure to be in 
the study. If you decide not to be in the study, which will not in any way harm your relations with 
your doctors or with Carolinas HealthCare System. You are free to stop being in the study if you 


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change your mind after entering it. This would not harm your relations with your doctors or 
Carolinas HealthCare System. Your decision will not result in any penalty or loss of benefits to 
which you are entitled. 
 
• You may always say no.  You do not have to take part in the study. 
• If you start a study, you may stop at any time.  You do not need to give a reason. 
• If you do not want to be in a study or you stop the study at a later time, you will not be 
penalized or lose any benefits. 
• If you stop, you should tell the study staff and follow the instructions they may give you. 
 
Your part in the research may stop at any time for any reason, such as: 
• The sponsor or the study doctor decides to stop the study. 
• The sponsor or the study doctor decides to stop your part in the study for your safety. 
• You need additional medicine. 
• You do not follow the study rules. 
• You have a new injury or illness. 
• You decide to stop. 
 
You may be asked to stop the study even if you do not want to stop.  
 
Should the medical staff find parts of the protocol not appropriate for you then you will be excluded 
from parts of the study. This is to protect your individual medical needs. We will tell you about new 
medical findings that may affect your willingness to continue in the study. 
 
CONFIDENTIALITY 
The records of this study will be kept private. In any sort of report we might publish, we will not 
include any information that will make it possible to identify a patient. Your record for this study 
may, however, be reviewed and/or photocopied by Carolinas HealthCare System, or by 
representatives of the Food and Drug Administration or other government agencies. To that extent, 
confidentiality is not absolute. 
 
To ensure that your information collected for this study will be kept private, your name will not be 
used whenever possible.  A code will be used instead of your name.  All of your study data will be 
kept in a secure location. 
 
AUTHORIZATION 
If you wish to take part in this clinical study, you will be asked to sign this consent form. It allows 
the study sponsor and the study investigator to collect and process any relevant personal health 
information collected from you during the study. These are activities routinely carried out during 
all clinical studies. 
 


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You have been told that personal information about you (including sensitive personal health 
information, such as your medical history and your racial/ethnic origin if relevant to the study) will 
be reviewed, collected on a computer database, stored in electronic or manual files, audited, and/or 
otherwise processed by: 
 
• 
The clinical study doctor and study staff 
• 
Regulatory or other governmental authorities of the United States and other countries 
• 
Carolinas HealthCare System employees 
• 
Other persons or agencies as required by law or allowed by federal regulations 
 
You have been told that your personal data are being collected and processed to: 
 
• 
Check your suitability to take part in the study 
• 
Compare and pool study treatment results with those of other subjects in clinical studies 
 
You have been told that your personal information may be processed within the U.S. or elsewhere in 
the world or transferred to or from the U.S. for review, processing and/or storage by an associated 
company or a carefully selected third-party organization. By signing this document, you explicitly 
consent to the transfer of your personal information, including sensitive personal information, 
collected during this clinical study, for review, processing and/or storage. Your personal health 
information may be further shared by the groups above. If shared by them, the information will no 
longer be covered by the Privacy Rule. However, the groups are committed to keeping your personal 
health confidential. 
 
You may refuse this authorization to transfer your personal information. If you choose not to agree 
to this authorization, you might be ineligible to participate in the study. If you decide not to sign this 
authorization, that will not harm your relations with your doctors or with Carolinas HealthCare 
System. 
 
You have the right to inspect your medical record at any time. Your research record may be 
unavailable until the conclusion of the study. At that point, it will be available. Please speak with the 
study doctor if you desire to access your record. 
 
You have been told whenever your personal information is processed; it will be kept confidential 
and secure, to the best of our ability. It will be used only for the purpose for which it was collected. 
 
This Authorization does not have an expiration date. You have been told that according to the 
guidelines for good clinical practice, the study investigator and sponsor will keep your personal 
information for at least 6 years. If you do not withdraw this Authorization in writing, it will remain 
in effect indefinitely. If you wish to revoke authorization to use your personal information, you will 
notify the study doctor, Kevin Kasten, MD (1025 Morehead Medical Drive, Suite 300 Charlotte, 
NC), in writing. Some of the data obtained from your record prior to your revocation may still be 
used if considered necessary for the study. 


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WHOM TO CONTACT ABOUT THIS STUDY 
During the study, if you experience any medical problems, suffer a research-related injury, or have 
questions, concerns or complaints about the study, please contact the Investigator at the telephone 
number listed on the first page of this consent document.  If you seek emergency care, or 
hospitalization is required, alert the treating physician that you are participating in this research 
study.   
 
An institutional review board (IRB) is an independent committee established to help protect the 
rights of research subjects.  If you have any questions about your rights as a research subject, and/or 
concerns or complaints regarding this research study, contact: 
 
• By mail: 
Study Subject Adviser 
Advarra IRB 
 
 
• or call toll free:        
 
• or by email:             
 
 
Please reference the following number when contacting the Study Subject Adviser: Pro00024189. 
 
 
 


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STATEMENT OF CONSENT  
 
I have read this form and its contents were explained to me.  I agree to be in this research study for 
the purposes listed above.  All of my questions were answered to my satisfaction.  I will receive a 
signed and dated copy of this form for my records.  I am not giving up any of my legal rights by 
signing this form.   
 
___________________________ 
____/____/____  _________ 
Signature of Research Subject 
 
Date 
Time 
 
___________________________________ 
Printed Name of Research Subject 
 
STATEMENT OF PERSON EXPLAINING CONSENT  
 
I have carefully explained to the subject the nature and purpose of the above study.  There has been 
an opportunity for the subject to ask questions about this research study.  I have been available to 
answer any questions that the subject has about this study. 
 
___________________________ 
____/____/____  _________ 
Signature of Person Explaining Consent 
Date 
 
Time 
 
___________________________________ 
Printed Name of Person Explaining Consent