Clinical trial NCT02186457
Conditions: Surgery Infection
Keywords: Pancreatoduodenectomy Whipple
Sponsor: Indiana University
Start date: 2014-11-01; Completion date: 2019-08-01
Enrollment: 190 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine if the routine use of antibiotic irrigation during pancreas surgery (Whipple procedure) will decrease superficial and organ space infections.

Detailed description:
The primary aim of this study is to test the efficacy of routine antibiotic irrigation in reducing superficial and organ space infections among patients undergoing pancreatoduodenectomy.

Arms: arm 1: Polymyxin B (500,000 U) in 1 liter of 0.9% Normal Saline arm 2: 0.9 % Normal Saline
Interventions: intervention 1: Polymyxin B in Normal Saline intervention 2: Placebo: Normal Saline
Intervention descriptions: intervention 1: Antibiotic irrigation via peritoneal lavage intervention 2: Placebo irrigation via peritoneal lavage

Protocol documents:
Prot_SAP_000.pdf: 
 
 
IUCRO-0463 
 
 
Version Date:  10/31/2014 
Page 1 of 16 
 
 
 
 
 
 
 
 
 
Routine Antibiotic Irrigation in Patients Undergoing 
Pancreatoduodenectomy to Reduce 
 Infection and Fistula Rates  
 
Protocol Number: 
IUCRO-0463 
 
Principal Investigator: 
Michael House, MD 
IU Department of Surgery 
545 Barnhill Drive, EH 525 
Indianapolis, IN 46202 
Phone: (317) 274-0113 
Email: michouse@iupui.edu 
 
Co-Investigators: 
Eugene Ceppa, MD 
Attila Nakeeb, MD 
C. Max Schmidt, MD 
Daniel Weber, MD 
Nicholas Zyromski, MD 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
IUCRO-0463 
 
 
Version Date:  10/31/2014 
Page 2 of 16 
 
Table of Contents: 
 
Study Schema 
1.0 
Background 
2.0 
Rationale and Specific Aims 
3.0 
Inclusion/Exclusion Criteria 
4.0 
Enrollment/Randomization 
5.0 
Treatment Plan 
6.0 
Study Calendar 
7.0 
Reporting of Adverse Events or Unanticipated Problems involving Risk 
to Participants or Others 
8.0 
Study Withdrawal/Discontinuation 
9.0 
Statistical Considerations 
10.0 Privacy/Confidentiality Issues 
11.0 Follow-up and Record Retention 
11.0 Data Safety Monitoring Plan 
12.0 References 
13.0 Appendices 
 


 
 
IUCRO-0463 
 
 
Version Date:  10/31/2014 
Page 3 of 16 
 
1.0 
Background 
 
Pancreatoduodenectomy, commonly referred to as a Whipple procedure, is a complex 
procedure performed for patients with both benign and malignant diseases of the 
periampullary region which consists of the head of the pancreas, the second portion of 
the duodenum near the ampulla of Vater, and the distal common bile duct.  Although 
mortality from the procedure is reported to be less than 5% in high volume centers, 
morbidity rates are much higher with reports indicating rates around 40% [1, 2].  Two 
of the most common complications contributing to this high morbidity rate include 
infections and pancreatic fistulae.  Studies have demonstrated that such complications 
have been associated with increased mortality rates in patients undergoing pancreatic 
surgery [3]. 
 
Many patients undergoing pancreatoduodenectomy already have a biliary stent in place 
draining their biliary system to prevent obstructive jaundice.  While these stents allow 
for decompression of an obstructed or soon-to-be biliary tree, they are also quick to 
colonize with enteric flora of the gastrointestinal tract.  Patients with preoperative stents 
have been shown to have higher wound infection and bacteremia rates [4].  Because 
pancreatoduodenectomy involves resection of the bile duct and construction of a biliary-
enteric anastomosis, it is quite likely that contaminated bile is present in the surgical 
field.  These bacteria sitting within the peritoneum are not appropriately treated by 
intravenous antibiotics and may contribute to local complications such as organ space 
infections, wound infections, and pancreatic fistulae.  
 
 
2.0 
Rationale and Specific Aims 
 
Antibiotic irrigation during abdominal surgery via peritoneal lavage is used commonly in 
abdominal surgery when there are concerns about contamination.  This technique offers 
the ability to decrease bacterial load, thereby potentially reducing intra-abdominal 
infections.  While irrigation typically consists of normal saline, several antibiotics have 
been used with varying degrees of success.  Recent literature in the field of colorectal 
surgery has demonstrated that the intraoperative use of antibiotic irrigation decreases 
wound complication rates to less than 5% compared to a rate of 14% among those 
receiving normal saline irrigation [5].   
 
Hypothesis: The routine use of intraoperative antibiotic irrigation during 
pancreatoduodenectomy will decrease superficial and organ space infections. 
 
Primary Specific Aim:  
• 
Test the efficacy of routine antibiotic irrigation in reducing superficial and organ 
space infections among patients undergoing pancreatoduodenectomy. 
 
 
Secondary Specific Aim: 
• 
Test the efficacy of antibiotic irrigation in reducing pancreatic fistula rates. 
  
 
 


 
 
IUCRO-0463 
 
 
Version Date:  10/31/2014 
Page 4 of 16 
 
 
 
3.0 
Inclusion/Exclusion Criteria 
 
Inclusion Criteria: 
1) At least 18 years of age and older. 
2) Open pancreatoduodenectomy for any diagnosis.   
 
Exclusion Criteria: 
1) Pregnant 
2) Prisoners 
3) Patients undergoing concomitant colectomy 
4) Antibiotic allergy to study medication 
5) Serum creatitine > 2.0 
6) Unable to provide informed consent 
 
 
4.0 
Enrollment/Randomization 
 
All patients will be registered with the Surgery Research Office. Regulatory files will be 
maintained by Surgery Research team and applicable regulatory documents must be 
completed and on file prior to registration of any patients.  
 
Screening and Informed Consent: Study personnel will identify the patients 
undergoing pre-operative evaluation at the surgical outpatient clinic (SOPA clinic). All 
eligible patients (fulfilling the inclusion criteria with no exclusion criteria) will be 
approached for informed consent.  
 
Randomization: Once consented, eligible patients will be randomized in a 1:1 ratio to 
treatment with either antibiotic irrigation or placebo irrigation under a blocked 
randomization scheme. Randomization lists will be prepared by the Department of 
Biostatistics.  When a subject is consented, the study coordinator will assign the patient 
a study subject number and inform the IDS pharmacist of the study number.  The 
pharmacist will then use the randomization list to assign the randomized medication. 
 
 
5.0 
Treatment Plan 
 
Study Medication: Randomized patients will receive the study drug or placebo 
intraoperatively during the reconstructive phase of the surgery.  The study drug will 
consist of Polymyxin B (500,000 U) in 1 liter of 0.9% normal saline and the placebo will be 
0.9% normal saline. In addition, all patients will receive one dose of parenteral 
antibiotics within 2 hours of the initial incision.  This will consist of 2 grams of 
intravenous ceftriaxone and 1 gram of intravenous flagyl.  For those patients who have 
allergic contradictions to this regimen, intravenous moxifloxacin (400mg) and 
clindamycin (600 mg) will be given.   
  
 
 


 
 
IUCRO-0463 
 
 
Version Date:  10/31/2014 
Page 5 of 16 
 
Administration of Study Medication: 
 
• 
The peritoneal irrigation solution will be manually lavaged over all intended peritoneal 
surface for a minimum of 60 seconds, but not to exceed 5 minutes. During the irrigation, 
the operating surgeon will “massage” the solution in the peritoneal surface for another 
minimum of 60 seconds, less than 5 minutes. The irrigation start and stop time will be 
recorded. Once this is completed, the residual solution will be cleaned up. 
 
At the end of the reconstructive phase of surgery: 
 
• 
One (1) Liter of either placebo or study medication will be gently irrigated 
directly at the pancreatojejunostomy anastomosis or at the 
pancreatogastrostomy anastomosis, if performed, upon its completion and then 
removed from the surgical field by suctioning.   
• 
One (1) liter of either placebo or study medication will be gently irrigated at the 
site of the choledochojejunostomy or hepaticojejunostomy anastomosis at its 
completion and then removed from the surgical field by suctioning.   
 
Administration of Parenteral Antibiotics: 
 
Within 2 hours (before or after) of initial incision: 
• 
One dose of parenteral antibiotics will be given 
 
 
Dosing Schedule: 
 
One (1) liter of study drug or placebo will be administered twice via peritoneal irrigation 
intra-operatively, once at the completion of the pancreatojejunal anastomosis or at the 
pancreatogastrostomy anastomosis and once at the completion of choledochojejunal or 
hepaticojejunal anastomosis.   
 
Blinding:  
 
The patient, treating surgeon, and research nurse coordinator will be blinded to the 
assigned treatment during the course of the study.  Upon randomization, the 
investigational pharmacy will prepare two one liter bags of normal saline solution, either 
with the antibiotic or just normal saline.  During the procedure, the solution will be 
provided and documentation of the treatment administered will be made as part of the 
investigational pharmacy documentation. 
 
 


 
 
IUCRO-0463 
 
 
Version Date:  10/31/2014 
Page 6 of 16 
 
6.0 
Study Calendar 
 
 
 
Baseline 
 
 
Surgery 
 
Follow up 
(-30 days-Day 
0) 
 
Day 0 
 
Day 
30 (+/- 
14 
days) 
Day 90 
(+/-14 
days) 
[Telephone 
Visit] 
REQUIRED ASSESSMENTS 
Medical history 
x 
 
 
 
Height, Wt 
x 
 
x 
 
Physical examination 
x 
 
x 
 
Vital Signs 
x 
  
x 
 
AE and concomitant medication 
assessment 
x 
x 
x 
 
Survival 
 
 
 
x 
TREATMENT 
Randomization 
x* 
 
 
Polymyxin B/Placebo Irrigation 
 
x 
 
x* randomization occurs after patient is registered to the study, prior to surgery 
 
 
Toxicities to be monitored in this study: 
 
Any evidence of allergic reaction to the antibiotic irrigation will be considered an adverse 
event. 
 
7.0 
Reporting of Adverse Events or Unanticipated Problems involving Risk 
to Participants or Others 
 
Definitions of Adverse Events 
 
Adverse Event (AE) 
 
An adverse event is defined as untoward medical occurrence associated with the use of a 
drug or procedure in humans, whether or not considered drug or procedure related. An 
adverse event can be ANY unfavorable and unintended sign, symptom, or disease 
temporarily associated with the use of a medicinal (investigational) product or procedure, 
whether or not considered related to the medicinal (investigational) product or procedure 
(attribution of ‘unrelated’, ‘unlikely’, ‘possible’, ‘probable’, or ‘definite’).  Examples of 
Adverse Events that will be recorded in this study are: 
 
• 
Concomitant illness 
• 
Physical injury 
• 
Events possibly related to medication 
• 
Significant worsening (change in nature, severity, or frequency) of the disease 
under study or other pre-existing conditions 


 
 
IUCRO-0463 
 
 
Version Date:  10/31/2014 
Page 7 of 16 
 
• 
Drug interactions 
• 
A laboratory or diagnostic test abnormality occurring shortly after the start of the 
study that results in the withdrawal of the patient from the study, requires 
medical treatment or further diagnostic work-up, or is considered by the study 
investigator to be clinically significant 
 
Adverse events will be graded according to the NCI Common Toxicity Criteria, Version 
4.0.  Delayed gastric emptying will be graded using the International Study Group of 
Pancreatic Surgery (ISGPS) system. 
 
 
Serious Adverse Event (SAE) 
 
A serious adverse event is any untoward medical occurrence resulting in one or more of 
the following: 
 
• 
Results in death or ANY death occurring within 28 days of last dose of study 
drug (even if it is not felt to be drug related)  
• 
Is life-threatening (defined as an event in which the patient was at risk of death 
at the time of the event; it does not refer to an event which hypothetically might 
have caused death if it were more severe) 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization 
NOTE: Hospitalizations that are not considered SAEs are:  
 
Hospitalization planned prior to first administration of study drug 
 
Hospitalization for elective treatment of a pre-existing condition 
unrelated to the study medication 
• 
Results in persistent or significant disability/incapacity 
• 
Is a congenital anomaly or birth defect 
• 
Is an important medical event (defined as a medical event(s) that may not be 
immediately life-threatening or result in death or hospitalization but,  based upon 
appropriate medical and scientific judgment, may jeopardize the patient or may 
require intervention (e.g., medical, surgical) to prevent one of the other serious 
outcomes listed in the definition above).  Examples of such events include, but 
are not limited to, intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions not resulting in 
hospitalization; or the development of drug dependency or drug abuse. 
 
 
Unexpected Adverse Event 
 
An adverse event not mentioned in the package insert or the specificity or severity of 
which is not consistent with the package insert. 
 
 
Determining Attribution to the Investigational Agent(s) 
 
Attribution: An assessment of the relationship between the AE and the medical 
intervention. CTCAE does not define an AE as necessarily “caused by a therapeutic 
intervention”. After naming and grading the event, the clinical investigator must assign 
an attribution to the AE using the following attribution categories: 


 
 
IUCRO-0463 
 
 
Version Date:  10/31/2014 
Page 8 of 16 
 
 
Relationship 
Attribution 
Description 
Unrelated to investigational 
agent/intervention 
Unrelated 
The AE is clearly NOT related 
Unlikely 
The AE is doubtfully related 
Related to investigational 
agent/intervention 
Possible 
The AE may be related 
Probable 
The AE is likely related 
Definite 
The AE is clearly related 
 
Adverse Event (AE) Reporting 
 
Adverse events (AEs) will be reported to the principal investigator immediately 
and will be recorded from the time of first study drug administration until 30 days 
after surgery, regardless of whether or not the event(s) are considered related to 
trial procedures or medications.  All AEs considered related to trial medication 
will be followed until resolution, return to baseline, or deemed clinically 
insignificant, even if this occurs post-trial. 
 
Reporting to the IRB:  
1. Unanticipated problems involving risks to subjects or others will be reported 
promptly to the IRB if they:  
• caused harm;  
• were unexpected;  
• were related or possibly related to the research intervention; AND  
• required revision to the informed consent document. 
 
If the serious adverse event does not meet all four (4) criteria listed above, the 
event does not have to be promptly reported to the Indiana University IRB.  
However, it will be reported at the time of continuing review. 
 
2. Prompt reporting of unanticipated problems to the IRB is defined as within 5 
days from becoming aware of the event. 
 
Reporting to the Data Safety Monitoring Committee (DSMC): 
Regardless of study sponsorship, the DSMC chair and/or coordinator will review 
all expedited SAE reports through OnCore®. Expedited reports are completed per 
IRB guidelines and may include the IRB Prompt Reporting form, non-compliance 
form. When follow-up information is received, a follow up report will also be 
created in OnCore.  The DSMC chair and/or coordinator will review expedited 
SAE reports monthly, and report findings to the DSMC.   
 
 
8.0 
Study Withdrawal/Discontinuation 
 


 
 
IUCRO-0463 
 
 
Version Date:  10/31/2014 
Page 9 of 16 
 
Subjects may be withdrawn from study participation at the discretion of the investigator 
or if the patient/surrogate or attending physician requests that the subject be 
withdrawn. The reason and date of every withdrawal will be recorded. The Informed 
Consent Document will notify participants that their participation is voluntary, and they 
can tell the study staff at any time if they decide to stop participating. In addition, if 
they choose to withdraw their authorization for study staff to access protected health 
information (PHI) in the medical record, they may do so by notifying study staff in 
writing. If a participant chooses to no longer participate but does not notify study staff 
that they withdraw authorization for access to PHI, their medical record may be 
accessed to obtain outcomes and safety data. Follow-up will be performed for all 
discontinuations due to an AE or other safety concern until resolution, until deemed 
chronic and stable, or as long as clinically appropriate. 
 
 
Definitions: 
 
Pancreatic fistulae will be defined by pre-existing definitions in the literature.  
 
 
In general, a pancreatic fistula is considered to be leak from the pancreatic 
ductal system.  More specifically, it is formally defined as an abnormal 
connection between pancreatic epithelium with another epithelial surface 
containing pancreatic fluid.  In the context of pancreatic surgery where a 
pancreatojejunal anastomosis is created and a surgical drain is utilized, a fistula 
likely indicates a failure of proper healing of the anastomosis and may not be 
connected to another epithelial surface but instead a drain [7].   
 
We will define a pancreatic fistula as output of at least 10mL/day of amylase-rich 
fluid (amylase content greater than 3 times the upper normal serum value) for 
greater than 5 days.  Accordingly, drains placed near the pancreatojejunostomy 
will have daily outputs and daily amylase levels checked on the first five days 
following surgery. 
 
 
Additionally, pancreatic fistulae are grading based on severity and will be 
classified as either grade A, grade B, or grade C as defined by the International 
Study Group on Pancreatic Fistula.  
• 
Grade A pancreatic fistulae are the most common are have limited to no 
clinical impact.  The patient appears clinical well, there no signs of infection 
or sepsis, there is typically no evidence of a fluid collection, drainage resolves 
and no specific treatment is indicated.   
• 
In contrast grade B fistulae require a change in clinical management; 
patients are made NPO (nothing by mouth) and supported with enteral or 
parenteral nutrition.  They require leaving pancreatic drains in place and will 
often necessitate a delay in discharge.   
• 
In patients with a grade C fistula, major deviations in management are 
required.  These patients may not be clinically stable and require aggressive 
interventions including care in the intensive care, nothing by mouth, 
supplemental nutrition, intravenous antibiotics and percutaneous drainage 
with a possible return trip to the operating room for repair, creation of a new 


 
 
IUCRO-0463 
 
 
Version Date:  10/31/2014 
Page 10 of 16 
 
anastomosis between the pancreas and the gastrointestinal tract, or 
completion pancreatectomy [7].  
 
Superficial and organ space infections are defined as follows from pre-exisiting 
definitions in the literature [6]: 
 
Superficial infections will be defined as an infection which occurs within 30 days 
after surgery and involves either skin/subcutaneous tissue (superficial) or the 
fascial/muscle layer (deep) of the incision.  Furthermore, the patient will need to 
meet at least one of the following criteria:  
1.  Purulent drainage from the incision but not from the organ/space component 
of the surgical site; 
2. Organisms isolated from an aseptically obtained culture of fluid or tissue from 
the superficial incision; 
3. At least one of the signs or symptoms of infection, including pain or 
tenderness, localized swelling, redness and heat and a superficial incision 
deliberately opened by a surgeon and either found to be culture-positive or not 
cultured (a culture-negative finding did not meet this criterion); 
4. A deep incision spontaneously dehisced or deliberately opened by a surgeon 
and either found to be culture-positive or not cultured (a culture-negative finding 
did not meet this criterion) and at least one of the signs or symptoms of fever 
(>38 °C), localized pain or tenderness; 
5. An abscess or other evidence of infection involving the deep incision found on 
direct examination, during reoperation, or by histopathologic or radiologic 
examination. 
 
Organ space infections will be defined as infections that occur within 30 days 
after surgery that is related to the surgery and involves any part of the body 
excluding that skin, fascia, or muscle layers, and meets at least one of the 
following criteria: 
1. Purulent drainage from a drain that was placed through a stab wound into the 
organ or space; 
2. Organisms isolated from an aseptically obtained culture of fluid or tissue in the 
organ or space; 
3. An abscess or other evidence of infection involving the organ or space found 
on direct examination, during reoperation, or by histopathologic or radiologic 
examination. 
4.  Any intraperitoneal collection requiring percutaneous drainage 
 
 
9.0 
Statistical Considerations 
 
The patients’ characteristics will be summarized by treatment arms and compared using 
two-sample t-tests for continuous and Chi-square test for categorical variables as 
appropriate. Nonparametric tests will be used if there is a normal distribution 
assumption violation. All analysis will be performed using SAS 9.3 (Cary, NC) 
 


 
 
IUCRO-0463 
 
 
Version Date:  10/31/2014 
Page 11 of 16 
 
Efficacy in reducing superficial and organ space infections:  In the primary analysis, 
proportion of patients with infection will be tabled and calculated for each arms and 
compared using a Chi-square test. In the secondary analysis, we will also use a logistic 
regression model with infection as the outcome variable, treatment arm as the main 
predictor, and will adjust for disease process in order to further evaluate the efficacy. 
 
Efficacy in reducing pancreatic fistula rates will be analyzed in a similar way to the 
primary outcome variable. 
 
Toxicity data related to the treatment will be summarized by treatment arm.  
 
Early Stopping Rule: 
An interim analysis will occur after 82 patients have been treated.  Overall complication rate and 
rate of major complication (e.g. Grade 3 through 5) will be analyzed for each treatment group at 
the interim analysis.  If the placebo group infection rate is three (3) times the infection rate of 
the treatment group, the study will be stopped. 
 
 
Sample Size and Statistical pow er: Historical data in hepatopancreatobiliary 
surgery show that the treated group will reduce primary outcome rate from 24% to 
8%. The anticipated reduction in infectious complications was estimated based on 
historical outcome data for abdominal operations involving one or more 
gastrointestinal anastomoses. Using a two-sided Chi-square test, we will need 82 
patients in each arm to detect such a difference with 80% power and 5% Type I 
error rate. With no attrition rate, we will need to recruit 164 patients totally.  The 
power analysis was performed for the primary endpoint only. 
 
 
10.0 
Privacy/Confidentiality Issues 
 
Patients will be consented in a private hospital room setting in order to protect 
confidentiality. 
 
 
11.0 
Follow-up and Record Retention 
 
Information stored in the database will be stored for an indefinite period of time for 
future reference, including for use in subsequent data analyses. Throughout the study, 
all collected data will be entered directly in to the secure password-protected web-based 
database.  In terms of study purposes, we will plan to follow for a 90 day period.  The 
90-day post operative visit will be a telephone visit. 
 
As stated in the informed consent document, participants’ consent to use or share PHI 
does not expire unless study staff has been explicitly notified of this decision in writing 
from the participant (even in the event that a subject withdraws from further 
participation).  
 
 
11.0 DATA SAFETY MONITORING PLAN 


 
 
IUCRO-0463 
 
 
Version Date:  10/31/2014 
Page 12 of 16 
 
 
DSMP for Moderate Risk Trials (Level 2)  
 
Moderate Risk Trials  
Investigators will conduct continuous review of data and patient safety. Monthly 
review meetings for Phase I/II and Phase II trials are required and will include the 
principal investigator, clinical research specialist and/or research nurse (other members 
per principal investigator’s discretion). Monthly meeting summaries will include review 
of data, the number of patients, significant toxicities as described in the protocol, and 
responses observed. Summaries will be submitted monthly and reviewed quarterly by 
the DSMC.  
 
Study Auditing and Monitoring  
All trials conducted at the IUSCC are subject to auditing and/or monitoring. Reports will 
be reviewed quarterly by the full DSMC (Reference Risk Table in full DSMC Charter).  
 
Early Study Closure  
At any time during the conduct of the trial, if it is the opinion of the investigators that 
the risks (or benefits) to the patient warrant early closure of the study, this 
recommendation will be made in writing to the Data Safety Monitoring Committee. 
Alternatively, the DSMC may initiate suspension or early closure of the study based on 
its quarterly review of the investigator reports.  
 
Reporting Guidelines  
The DSMC has streamlined the reporting process by utilizing reports from OnCore. This 
has allowed direct view of reports within the Clinical Trials Management System (CTMS); 
thus discontinuing paper reports. SAE reports are entered into OnCore monthly and 
reviewed by the DSMC chair and/or coordinator monthly. Findings will be reported to the 
full DSMC quarterly.  
 
Reporting Death:  
Death will be reported per local IRB reporting guidelines. The DSMC will review all 
reported deaths monthly.  
 
Study Accrual Oversight  
Accrual data will be entered into the IU Simon Cancer Center OnCore system on a 
monthly basis. The Protocol Accrual Committee (PAC) reviews study accrual twice per 
year while the PAC coordinator reviews accrual quarterly. 
 
Protocol Deviations  
Protocol deviations are entered into OnCore monthly and reviewed by the DSMC chair 
and/or coordinator monthly. Findings will be reported to the full DSMC quarterly. 
 
 
 


 
 
IUCRO-0463 
 
 
Version Date:  10/31/2014 
Page 13 of 16 
 
12.0 References: 
 
1. 
Yeo, C.J., et al., Six hundred fifty consecutive pancreaticoduodenectomies in the 
1990s: pathology, complications, and outcomes. Ann Surg, 1997. 226(3): p. 248-
57; discussion 257-60. 
2. 
Schmidt, C.M., et al., Pancreaticoduodenectomy: a 20-year experience in 516 
patients. Arch Surg, 2004. 139(7): p. 718-25; discussion 725-7. 
3. 
Kelly, K.J., et al., Risk stratification for distal pancreatectomy utilizing ACS-
NSQIP: preoperative factors predict morbidity and mortality. J Gastrointest Surg, 
2011. 15(2): p. 250-9, discussion 259-61. 
4. 
Howard, T.J., et al., Influence of bactibilia after preoperative biliary stenting on 
postoperative infectious complications. J Gastrointest Surg, 2006. 10(4): p. 523-
31. 
5. 
Ruiz-Tovar, J., et al., Effect of peritoneal lavage with clindamycin-gentamicin 
solution on infections after elective colorectal cancer surgery. J Am Coll Surg, 
2012. 214(2): p. 202-7. 
6. 
Ceppa, E.P., et al., Reducing surgical site infections in hepatopancreatobiliary 
surgery. HPB (Oxford), 2013. 15(5): p. 384-91. 
7. 
Bassi, C., et al., Postoperative pancreatic fistula: an international study group 
(ISGPF) definition. Surgery, 2005. 138(1): p. 8-13. 
 
 
 
 


 
 
IUCRO-0463 
 
 
Version Date:  10/31/2014 
Page 14 of 16 
 
13.0 APPENDICES 
13.1 APPENDIX I-TOXICITY CRITERIA 
NOTE:  the attached Appendix I contains reference to the DCT/NCI Common 
Toxicity Criteria, Version 4.0, used to grade toxicities in reporting an "ADR" 
(adverse drug reaction) as described in Section 15.0 of this protocol.  Other 
toxicity criteria (i.e., related to specialized treatments such as immunotherapy or 
BRMs) may be used as needed. 
 
13.2 APENDIX II-CTMC CHECK SHEET 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
IUCRO-0463 
 
 
Version Date:  10/31/2014 
Page 15 of 16 
 
Appendix I 
 
NCI Common Toxicity Criteria  
 
Version 4.0 
 
 
Due to the size of the latest version of the Common Toxicity Criteria, copies of this 
appendix are not included with this protocol document. 
 
An electronic copy is available on the CTEP web site, 
http://ctep.cancer.gov/reporting/ctc.html 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
IUCRO-0463 
 
 
Version Date:  10/31/2014 
Page 16 of 16 
 
Appendix II 
CTMC Check Sheet 
Y
N
N/A
*Notes
Has accrual been entered into Oncore for all IUSCC programs per the "Data Requirements for Cancer Center 
Reporting"  SOP
Deviation Log reviewed, discussed and signed by ALL team members including PI                                                       
Has patient safety data been discussed/reviewed? Have  all SAE's and deviations been reported in Oncore for 
all IUSCC programs. 
Has all data been entered into Oncore per the "Data Requirements for Cancer Center Reporting"  SOP? 
Weekly and Monthly meetings should include discussion on data, patient safety, dose levels, accrual 
numbers, significan toxicities, dose adjustments and responses observed, deviation summaries and SAE 
reports. (per IUSCC DSMP)
Meeting Date: 
Protocol & Status (open/closed to accrual)
PI:
CRS:
Team/Program: (include meeting sign in sheet)