Short Versus Long Interval to Ileostomy Reversal After Ileal Pouch Surgery for Ulcerative Colitis
Phase: NA
Conditions: Ulcerative Colitis, Ileal Pouch, Ileostomy - Stoma
Sponsor: University of Colorado, Denver

Short versus long interval to loop ileostomy reversal after 
ileal pouch surgery in patients with ulcerative colitis 
(SLIRPS) trial 
A randomized, prospective trial investigating the timing of diverting ileostomy 
closure after ileal j-pouch surgery.   
 
Protocol Version 3.3, October 11, 2019 
Sponsor/Principal Investigator:  
 
Jon D. Vogel, MD 
Division of Gastrointestinal Trauma & Endocrine Surgery 
Section of Colon & Rectal Surgery 
University of Colorado 
Phone: 303 724-2728 
Fax: 303 724-2733 
email: jon.vogel@cuanschutz.edu 
 
Co-Investigators (updated 
02/09/2021): 
 
1. Philip Fleshner, MD.  Cedars Sinai, Los Angeles 
2. Giovanna DaSilva, MD. Cleveland Clinic Florida 
3. Stephan Holubar, MD.  Cleveland Clinic Ohio 
4. Vitaily Polylin,MD. Northwestern University 
5. Neil Hyman, MD.  University of Chicago 
6. Scott Regenbogen, MD.  University of Michigan 
7. Matthew Mutch, MD.  Washington University, St. Louis 
8. E. Messaris, MD.  Beth Israel, Boston 
 
 
  
Biostatistician 
Patrick Hosokawa, PhD 
University of Colorado  
Email: Patrick.Hosokawa@cuanschutz.edu 
 
Lead Study Coordinator 
Tracey MacDermott 
Department of Surgery 
University of Colorado 
Phone:  303 724-2757 
Fax: 303 724-2733 
Email: Tracey Macdermott@cuanschutz.edu 
 
Data Management Center 
University of Colorado 
Name:  Tracey MacDermott 
Phone: 303 724-2757 
Fax: 303 724-2733 
Email: Tracey Macdermott@ cuanschutz.edu 
 
Funding Agent 
Crohn’s & Colitis Foundation 
 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
2
1 
SUMMARY 
4 
2 
INTRODUCTION AND BACKGROUND 
8 
JUSTIFICATION AND OBJECTIVES OF THE CLINICAL TRIAL 
9 
3 
PATIENT SELECTION 
10 
Inclusion criteria 
10 
Exclusion criteria 
10 
Overview of time sequence 
11 
4 
DESCRIPTION OF THE CLINICAL TRIAL SEQUENCE 
13 
Screening visit 
13 
PHASE 1, IPAA Surgery 
14 
PHASE 1, IPAA Clinical Assessment 
15 
PHASE 2, IPAA Radiological Assessment 
16 
PHASE 2, Ileostomy Closure 
16 
PHASE 2, Outcome Assessment 
16 
5 
ADVERSE EVENTS 
17 
6 
DOCUMENTATION AND REPORTING OF ADVERSE EVENTS 
19 
Documentation and Reporting of Serious Adverse Events 
22 
7 
WITHDRAWAL OR STOP OF STUDY CRITERIA 
23 
Criteria for the termination of the whole study 
24 
8 
DATA SAFETY MONITORING 
24 
9 
RANDOMIZATION, DATA MANAGEMENT AND DATA MONITORING 
24 
13 
STATISTICAL CONSIDERATIONS 
26 
Sample Size Calculation 
26 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
3
Statistical analyses 
26 
DSMB interim analyses and early stopping rules for interim analyses 
27 
14 
REFERENCES 
28 
15 
APPENDIX 
30 
Table:  Clavien-Dindo 
30 
Illustrations:  IPAA surgery 
31 
Timeline of study visits 
32 
Clinical Adverse Event Reporting Form 
34 
 
Case Report Forms 
 
 
 
 
 
 
 
 
35 
 
 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
4
1 SUMMARY 
Title: 
Short versus long interval to loop ileostomy reversal after ileal 
pouch surgery in patients with ulcerative colitis (SLIRPS) trial 
Research 
Hypothesis: 
In patients with ulcerative or indeterminate colitis who undergo ileal 
pouch anal anastomosis and diverting loop ileostomy (IPAA) 
surgery a short interval to loop ileostomy reversal will result in 
differences in complications and quality of life compared to a long 
interval to loop ileostomy reversal. 
Phase: 
III 
Study design: 
Prospective, randomized, multicenter 
Study population: 
Adult patients with ulcerative colitis (UC) or indeterminate colitis 
(IC) who will undergo ileal j-pouch surgery.  
Sample size: 
126-152 patients 
Treatment: 
Phase 1: 
 Colorectal excision, ileal j-pouch, & diverting ileostomy 
surgery 
Phase 2:   
 Diverting ileostomy closure surgery 
Treatment 
duration: 
Phase 1 will have a treatment duration of approximately 6 weeks 
that will begin after informed consent #1 is obtained and will end 
within 1 week of ileal j-pouch surgery. Phase 2 will have a duration 
of approximately 6 months and will begin after informed consent #2 
is obtained. 
Criteria for 
inclusion: 
 Signed informed consents. 
 Man or woman between 18 and 64 years of age. 
 UC or IC diagnosed by routine clinical, radiographic, 
endoscopic, and pathological criteria. 
 Patient will be scheduled for non-emergent proctocolectomy or 
completion proctectomy with ileal j-pouch anal anastomosis 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
5
(IPAA) and loop ileostomy (IPAA). 
 Clinical assessment of patient after IPAA surgery indicates that 
patient is suitable for early ileostomy reversal 
Criteria for 
exclusion: 
 Age < 18 or > 64 years 
 Body mass index (BMI) equal or above 40 kg/m2 
 Crohn's disease or suspected Crohn's disease 
 Known previous or concurrent malignancy (other than that 
considered surgically cured, with no evidence for recurrence 
for 5 years).  A recent history of basal cell or squamous cell 
carcinoma does not exclude the subject. 
 Pregnant patients and female patients who do not satisfy the 
standard of care requirements of participating centers for an 
elective surgical procedure. 
 Hemodynamic instability (persistent pulse rate  < 50 or > 120 
bpm, systolic blood pressure < 90 or > 160 mm Hg, 
uncontrolled cardiac arrhythmia, or active vasopressor drug 
use) 
 Systemic sepsis 
 Organ transplant recipient (e.g. Liver, Kidney, Pancreas) 
 Immunosuppression due to chemotherapy drug use or 
systemic disease. 
 Prednisone dose > 20 mg per day (or equivalent other steroid 
dose) within 4 weeks of scheduled IPAA 
 
Patients with ongoing C. difficile colitis 
 
Patients with pre-existing hepatic disease and portal 
hypertension 
 
Patients with pre-existing renal dysfunction (creatinine >1.7 
mg/dl) 
 
Patients with poorly controlled pre-existing chronic lung 
disease 
 
Therapeutic anticoagulation or coagulopathy (PTT or INR 
above normal range) 
 
Blood Hemoglobin < 8 g/dl 
 
Serum Albumin < 2.5 g/dl 
 
Clinical assessment of patient after IPAA surgery indicates 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
6
that patient is not suitable for early ileostomy reversal 
 
Participation in another clinical IBD drug trial within the last 30 
days, or simultaneous participation in another clinical trial 
 
Well-founded doubt about the patient’s cooperation 
 
Individualized decision by the surgeon to exclude the patient 
based on sound surgical judgment  
 
Criteria for 
Evaluation:  
A 
confirmed 
or 
presumed 
diagnosis 
of 
ulcerative 
or 
indeterminate/undetermined colitis will be determined by the study 
surgeons.  The diagnosis will be based on the constellation of 
clinical, endoscopic, and pathology results that are used in routine 
practice to establish a diagnosis of these conditions.  
Primary variables 
Comprehensive 
Complication 
Index 
at 
6 
months 
after 
randomization.     
Secondary 
variables: 
(1) Total number of postoperative complications per patient; (2) 
Percent of patients with complications; (3) Total number of stoma 
related complications per patient; (4) Health-related quality of life; 
and (5) IPAA functional outcomes (all at 6 months after 
randomization). 
Statistical 
analysis: 
A Consort Diagram will be used to account for all patients screened 
for inclusion in the trial; those who were excluded and included and 
reasons for exclusion; those who were randomized; and those who 
were followed at each time point or who were lost to follow-up.  The 
primary analysis will be by intention-to-treat, meaning that the 
patients will be analyzed by the group to which they were 
randomized.  This means that patients randomized to the short 
interval closure group who have postoperative complications that 
delay closure will still be analyzed in the group to which they were 
randomized.  Secondary analyses will be done per-protocol 
(analyzing patients who followed the protocol), and as-treated 
(analyzing patients by the treatment they actually received). 
Patient baseline characteristics will be compared between the early 
and late closure groups using a chi-square test for categorical 
variables and a t-test for independent samples for normal 
continuous variables or a Wilcoxon two sample ranks test for non-
normal continuous variables. 
Complications 
will 
be 
reported 
using 
the 
Clavien-Dindo 
classification.  Perioperative details in the two groups will be 
compared using the same methods as were used for comparing the 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
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patient baseline characteristics. 
The 
primary 
analysis 
will 
be 
comparing 
Comprehensive 
Complication index and overall complication rates up to 6 months 
postoperatively between the two randomized groups using a 
generalized linear model with a log-link function with group (short 
vs. long interval closure) and hospital as the independent variables.  
We will also include any patient baseline characteristics that 
remained unbalanced in spite of randomization.  Secondary 
analyses will include a comparison of mean number of 
complications per patient using a zero-inflated Poisson model, and 
a comparison of severe complications (Clavien-Dindo Grade IIIa or 
higher) using the same methods as were used for the primary 
analysis.  We will also compare the mean number of stoma related 
complications using a zero-inflated Poisson model.  Since the 
quality of life scales are continuous variables measured over time, 
we will compare the early vs. late closure groups for these 
outcomes using linear mixed models. 
Duration of study 
Duration per patient will be approximately 7 months. The 
anticipated time of the overall study duration is approximatly 18 
months 
Number of 
centres: 
17-25 centers in United States 
 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
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2 INTRODUCTION AND BACKGROUND 
Ulcerative colitis (UC) and indeterminate colitis are chronic inflammatory 
gastrointestinal disorders, which are limited to the colon and characterized by the 
involvement of the mucosa only (in contrast to the transmural inflammation seen in 
CD). UC primarily affects young adults (20 - 40 years) but may present also at a 
very early age (5-10 years) or in later in life (>60 years). The inflammatory process 
in UC and IC is primarily localized to the rectum (proctitis) or can extend proximally 
in a contiguous manner involving the mucosa up to the splenic flexure (left sided 
colitis) or involving the entire colon (extensive colitis). A key clinical feature of UC 
and IC is bloody diarrhea. The clinical course of UC and IC is characterized by 
periods of spontaneous exacerbation (acute flares) and remission (50 - 80% of 
patients) while some patients have a continuous active disease course (15 - 30% of 
patients) and others develop severe colitis (5 - 10% of patients), which can result in 
colectomy if medical therapy is not effective. Long standing UC and IC is associated 
with an increased risk of colorectal cancer; the use of 5-ASA products may reduce 
this risk. UC and IC can also be associated with inflammation involving extra-
intestinal sites such as the skeletal, skin, or biliary system.   
 
A “defunctioning” loop ileostomy is routine to the practice of colorectal surgery.  In 
general, this type of ileostomy is put in place to direct the enteric contents away 
from a newly created surgical anastomosis that is downstream (distal) to the 
ileostomy.  For example, a defunctioning loop ileostomy is routinely made during 
ileal pouch anal anastomosis (IPAA) surgery to facilitate healing of the IPAA.   It is 
common practice to leave the diverting ileostomy in place for 8 to 12 weeks with the 
idea that this interval is needed to ensure complete healing of the anastomosis.  
After 8 to 12 weeks, an imaging study (e.g. contrast enema) is performed to confirm 
complete healing of the anastomosis.  After that, so long as healing of the 
anastomosis has occurred, the diverting ileostomy is surgically reversed.  While 
potentially beneficial to the healing process, a diverting ileostomy may also be 
detrimental to the health and well-being of the patient.  Potential detriments include 
dehydration, leakage from the ileostomy with resultant skin irritation and 
interference with activities of daily living, ileostomy dysfunction, and its negative 
impact on both physical and emotional function and quality of life.  In an ideal 
situation, the diverting ileostomy would be left in place for an adequate period to 
facilitate healing of the anastomosis, while closing the ileostomy at the earliest 
appropriate time point in order to minimize the risks associated with an ileostomy.   
 
The primary outcome variable for the study will be the Comprehensive Complication 
Index (CCI).  The CCI is a novel continuous scale to measure surgical morbidity that 
has been developed in the past few years. (Slankamenac, 2013)  It is based upon a 
survey of patients, nurses, and surgeons measuring their perceptions of the 
seriousness of 30 postoperative complications common in abdominal surgery 
(Slankamenac, 2011).  From this survey, a score between 0 (no complications) and 
100 (death) was developed to measure the occurrence of one or more 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
9
postoperative complications in abdominal surgery patients, taking into account the 
number and seriousness of the complications.  The score has been validated using 
four different methods (K. Slankamenac, 2013), and has been applied to the 
databases from 3 different randomized surgical trials and shown to be useful in 
reducing required sample sizes in surgical clinical trials (K. Slankamenac, 2014)  
 
Quality of life and functional outcomes of IPAA in patients with ulcerative colitis have 
been evaluated in retrospective studies. (Delaney 2003, Farouk 2000)  The SF-12 is 
a validated quality of life measurement tool that has been used to evaluate patients 
who have undergone colorectal resection. 
JUSTIFICATION AND OBJECTIVES OF THE CLINICAL TRIAL 
Randomized prospective trials have evaluated the outcomes of standard (8 weeks) 
and decreased (8-13 day) intervals to defunctioning ileostomy reversal after rectal 
cancer surgery and have demonstrated superiority of decreased interval to closure. 
[Danielsen 2017; Alves 2008] The unique significance of our study is that it will 
focus on ulcerative colitis patients who undergo ileal pouch surgery with temporary 
defunctioning ileostomy.   
 
This operation is performed on a minimum of 15 patients, with UC or IC, annually at 
University of Colorado Hospital and at the co-investigator centers.  This surgery is 
performed by fellowship-trained and board certified colorectal surgeons at the 
University of Colorado. 
 
Hypothesis:  In patients with ulcerative or indeterminate colitis who undergo ileal 
pouch anal anastomosis and diverting loop ileostomy (IPAA) surgery* a short 
interval to loop ileostomy reversal will result in differences in complications and 
quality of life compared to a long interval to loop ileostomy reversal.  
*For clarification, please see illustrations and images at end of this document 
Aim #1:  To compare the Comprehensive Complication Index (CCI),  the incidence 
of postoperative complications, including total number of complications per patient, 
percent of patients with complications, and total number of ostomy-related 
complications per patient  among IPAA patients who have their ileostomy reversed 
after a short interval compared to a long interval.   
Aim #2:  To compare the short vs. long interval groups on measures of health-
related quality of life (SF-12) and IPAA functional outcomes    

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
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3 PATIENT SELECTION 
Inclusion criteria 
 Signed informed consent 
 Patient age 18 to 64 years 
 Confirmed or presumed diagnosis of ulcerative colitis or, 
indeterminate/undetermined colitis* 
 Patient will be scheduled for non-emergent proctocolectomy or completion 
proctectomy with ileal j-pouch anal anastomosis (IPAA) and loop ileostomy 
(IPAA). 
 Clinical assessment of patient after IPAA surgery indicates that patient is suitable 
for early ileostomy reversal 
 
Exclusion criteria 
Patients who meet one of the following criteria are to be excluded from the trial: 
 
 Age < 18 or > 64 years 
 Body mass index (BMI) equal or above 40 kg/m2 
 Crohn's disease or suspected Crohn's disease 
 Known previous or concurrent malignancy (other than that considered 
surgically cured, with no evidence for recurrence for 5 years).  A recent history 
of basal cell or squamous cell carcinoma does not exclude the subject. 
 Pregnant patients and female patients who do not satisfy the standard of care 
requirements of participating centers for an elective surgical procedure. 
 Hemodynamic instability (persistent pulse rate  < 50 or > 120 bpm, systolic 
blood pressure < 90 or > 160 mm Hg, uncontrolled cardiac arrhythmia, or 
active vasopressor drug use) 
 Systemic sepsis 
 Organ transplant recipient (e.g. Liver, Kidney, Pancreas) 
 Immunosuppression due to chemotherapy drug use or systemic disease. 
 Prednisone dose > 20 mg per day (or equivalent other steroid dose) within 4 
weeks of scheduled IPAA 
 
Patients with ongoing C. difficile colitis 
 
Patients with pre-existing hepatic disease and portal hypertension 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
11
 
Patients with pre-existing renal dysfunction (creatinine >1.7 mg/dl) 
 
Patients with poorly controlled pre-existing chronic lung disease 
 
Therapeutic anticoagulation or coagulopathy (PTT or INR above normal 
range) 
 
Blood Hemoglobin < 8 g/dl 
 
Serum Albumin < 2.5 g/dl 
 
Clinical assessment of patient after IPAA surgery indicates that patient is not 
suitable for early ileostomy reversal 
 
Participation in another clinical trial within the last 30 days, or simultaneous 
participation in another clinical trial 
 
Well-founded doubt about the patient’s cooperation 
 
Individualized decision by the surgeon to exclude the patient based on sound 
surgical judgment  
Overview of time sequence 
 
1. PHASE 1 (-30 to 0 days):  Screening Visit and Informed Consent #1:  
Assessment and documentation of initial inclusion and exclusion criteria will 
occur during the IPAA preoperative assessment clinic visit.  A brief oral and 
written description of the trial will be presented to subjects who satisfy the 
initial inclusion/exclusion criteria and express interest in participation.  These 
patients will be asked to review and sign informed consent #1 for SLIRPS 
trial participation.  Case report form-1 (CRF-1, screening) will be completed 
at this time.  The assessment will be performed by the study surgeon or 
study assistant at each site.  
 
2. PHASE 1 (day 0):  IPAA Surgery (See Illustrations at end of protocol): 
a. The use of a mechanical and/or oral antibiotic bowel preparation will be 
the discretion of the study surgeon, and will be documented in the 
appropriate study form.  The same will apply to the preoperative use of 
intravenous prophylactic antibiotics and venous thromboembolism 
prophylaxis.  “pre-IPAA” data points of interest will be recorded in CRF 2 
by the study surgeon or trial assistant within 3 days of IPAA surgery.   
b. The IPAA surgery, including ileostomy creation, will be performed by the 
study surgeon in a manner that is consistent with accepted and standard 
surgical practice.  The use of laparoscopic, hand-assisted laparoscopic, 
robotic, open, or other surgical techniques will be at the discretion of the 
study surgeon and will be recorded in CRF-3 (IPAA surgery details) by 
the study surgeon or trial assistant within 3 days of the IPAA surgery. 
 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
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3. PHASE 1 (day 5 to 12):  IPAA Clinical Assessment:  On day 5-12 after 
IPAA surgery, the surgeon performs a routine “clinical assessment” of the 
patient and determines if the patient is suitable or not suitable for early 
ileostomy closure.  (CRF 4, IPAA Assessment).  
a. Study patients judged not suitable for early ileostomy closure are 
excluded from the study.  Documentation of the reasons for 
“unsuitability” will be captured on CRF-4 (IPAA assessment).   
b. Study patients judged suitable for early ileostomy closure will be asked 
for informed consent to participate in the trial. 
 
4. PHASE 2 (day 5 to 12):  INFORMED CONSENT #2:  Study patients judged 
clinically suitable, by the study surgeon, for early ileostomy closure, will be 
ask to review and sign informed consent #2 for SLIRPS trial participation.   
Oral and written description of the trial will be presented to subjects who 
satisfy the inclusion criteria and initial and secondary exclusion criteria and 
express interest in participation.  Consent will be obtained by the study 
surgeon or assistant at each site.  After informed consent is obtained, the 
patient will be registered into the trial. 
 
5. PHASE 2 (day 5 to 12):  IPAA Radiological Assessment will be performed 
on day 5-12 after IPAA on all study patients who are determined by the study 
surgeon to be clinically suitable for early ileostomy closure and who have 
provided informed consent (#1 and #2) to participate in the trial.   
a. Radiologic assessment will be performed at day 5 to 12 after IPAA 
ostomy surgery.   CT or fluoroscopic imaging of the IPAA with a water-
soluble contrast medium will be performed to visualize the IPAA and 
determine the presence of radiologic leak.  With either imaging 
modality, the enema contrast medium is instilled using a soft catheter.   
b. Subjects not radiologically suitable for early ileostomy reversal:  
Study patients with a radiological leak from the IPAA will not be 
randomized to early or late closure.   Details of the radiologic leak will 
be captured in CRF-4 (IPAA assessment).  The patient will not be 
randomized to control or experimental trial arms.  Treatment of these 
patients will follow the standards of care.  
c. Subjects radiologically suitable for early ileostomy reversal:  
Study patients with no radiologic leak from the IPAA will be 
randomized to the control or experimental study arms.  (CRF-4) 
 
6. PHASE 2 (day 5 to 12):  RANDOMIZATION:  Immediately after IPAA 
radiologic assessment, study patients with no radiologic leak will be 
randomized to early (post-IPAA day 7 to 12) or late (post-IPAA ≥ 8 weeks) 
ileostomy closure via the REDCap data collection system.  The 
randomization scheme will be established by the study biostatistician.  The 
randomization will be stratified by study site.  Within each site, randomly 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
13
selected block sizes of 2, 4, or 6 will be used so that the site investigators 
cannot predict beforehand the group to which the patient will be randomized. 
 
7. PHASE 2 (day 7 to 12 or week 8-12):  Ileostomy Closure:   
a. Early ileostomy closure will be performed at 7 to 12 days after IPAA.   
b. Late ileostomy closure will be performed 8 - 12 weeks after IPAA.    
c. The ileostomy closure surgical technique is at the discretion of the 
surgeon.   
d. CRF-5 (ileostomy reversal details) will be completed within 3 days of 
ileostomy reversal surgery. 
e. Endoscopic examination (optional):  Rigid and/or flexible endoscopic 
examination of the IPAA may be performed per standard 
practice/standard of care, including non-study-related informed 
consent, at the discretion of the study surgeon following standard of 
care. (CRF-5) 
 
8. PHASE 2 (day 7 – 12 to 6 months):  Outcome assessment:   
a. The Comprehensive Complication Index and postoperative 
complications will be assessed and recorded by the study surgeon or 
trial assistant after review of the medical record, conversation with 
patient, and members of the care team (when appropriate).  This 
assessment and documentation will begin immediately after 
randomization is performed and will be updated at 1-2 month intervals 
until 6 months after randomization. (CRF-6) 
b. Functional outcomes and quality of life (CRF-7):  IPAA functional 
outcomes and quality of life (SF-12) will be assessed and recorded 
once at 6 months after ostomy reversal.  
 
4 DESCRIPTION OF THE CLINICAL TRIAL SEQUENCE 
Screening visit 
Data to be recorded: 
General parameters: 
 Initials 
 Age 
 Gender 
 ASA 
 BMI 
 Hemoglobin (g/dl) 

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 Serum Albumin (g/dl) 
 Active smoker (smoking within 1 month of IPAA) 
 Bowel Preparation (choose:  none, mechanical only, oral antibiotic only, 
mechanical AND oral antibiotic)Date of birth 
 
Case history 
Medication Use 
 Anti TNF drug use within 8 weeks of IPAA surgery date 
 Steroid use within 4 weeks of IPAA surgery date (excluding Budesonide) 
 Vedolizumab drug use within 8 weeks of IPAA surgery date 
 Other colitis drugs (e.g. methotrexate, azathioprine, 5-ASA) within 4 weeks of 
IPAA surgery date 
 
Examinations 
 Vital signs: blood pressure (mm Hg), heart rate (min-1), weight (kg), calculation 
of BMI 
 Physical examination: Routine preoperative examination 
 Blood draw:  blood hemoglobin, serum albumin,  other blood tests at discretion 
of surgeon 
 
Formal aspects: 
Informed consent procedure 
Verification of inclusion / exclusion criteria (eligibility check), as far as possible 
 
PHASE 1, IPAA Surgery 
IPAA surgery type 
 Proctocolectomy with IPAA (2-stage procedure) 
 Completion proctectomy with IPAA (3-stage procedure) 
 
Indication for proctocolectomy or colectomy 
 Colitis symptoms inadequately controlled by medical therapy or steroid-
dependence 
 Colorectal epitheial dysplasia 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
15
 
Urgency of colectomy or proctocolectomy 
 Urgent (colectomy or proctocolectomy performed on a hospitalized patient) 
 Elective (colectomy or proctocolectomy performed on a patient who was not 
hospitalized on the day before surgery) 
IPAA Surgery Details 
 Duration of surgery (cut to close, minutes) 
 Open removal of colon and rectum 
 Laparoscopic proctocolectomy  
 Laparoscopic colectomy with open proctectomy 
 Hand assisted laparoscopic (HAL) proctocolectomy  
 HAL colectomy colectomy with open proctectomy 
 Robotic proctocolectomy  
 Robotic colectomy with open proctectomy 
 Lap, HAL, or Robotic proctocolcetomy or colectomy with unplanned conversion  
to open surgery 
 Trans-anal-trans-abdominal IPAA 
 Stapled IPAA 
 Sutured IPAA 
 IPAA anastomotic leak test performed (yes/no) 
 IPAA anastomotic leak test result:  no leak, small leak, big leak 
 Ileal pouch bleeding that required suture placement or other methods to stop 
bleeding 
 IPAA tension (none, minimal, moderate) 
 EBL 
 Injury to surrounding structures (specify, enterotomy, ureter injury, pelvic 
hemorrhage, etc.) 
 Sepra Film wrap of ileostomy 
 Epidural anesthesia 
PHASE 1:  IPAA Clinical Assessment  
 Post-IPAA day that clinical assessment was performed 
 Review / confirmation of inclusion exclusion criteria 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
16
 Informed consent #2 obtained (only for patients determined to be clinically 
suitable for early ileostomy reversal) 
 Not ready ileostomy reversal (explanation-comment and Clavien Dindo 
classification if applicable) 
 
PHASE 2:  IPAA Radiological Assessment 
 Post-IPAA day that radiologic assessment was performed 
 CT with rectal contrast (yes or no) 
 Contrast enema (yes or no) 
 Radiologic exam OK (Yes or No) 
 Randomization to early or late ileostomy closure study arms 
 Radiologic exam not OK and patient will NOT be randomized to experimental 
or control trial arms (explanation required) 
 Explanation for no randomization 
 Radiologic leak (yes or no, if yes, Clavien-Dindo classification if applicable) 
 Other reason for no randomization 
 
PHASE 2:  Ileostomy Closure 
   Duration of surgery (cut to close, minutes) 
   Stapled ostomy closure 
   Sutured ostomy closure 
   Ostomy site skin complete closure 
   Ostomy site skin partial closure (e.g. pursestring) 
   Ostomy site skin not closed 
   Endoscopic examination of IPAA (no, yes, comments) 
 
 
PHASE 2:  Outcome Assessment 
 IPAA stenosis requiring more than simple digital dilation 
 Small Bowel Obstruction (imaging confirmed) 
 Ileus 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
17
 Venous Thromboembolism 
 Lung or Heart-related complications 
 Hemorrhage requiring transfusion 
 high output ileostomy 
 Peristomal skin irritation 
 Peristomal infection 
 ileostomy prolapse 
 ileostomy stenosis 
 ileostomy revision necessary 
 ileostomy leakage 
 ileostomy dusfunction 
 
Readmission 
 Total # of inpatient hospital days 
 Total # of hospital admissions 
 
Comprehensive Complication Index: web-based calculation 
 
5 ADVERSE EVENTS 
Definitions 
Adverse events (AEs) 
Adverse events (AEs) will be recorded at each regular scheduled study visit or study 
phone contact in the patient record (source document) as well as on a specific AE 
form on the electronic CRF. 
An AE is any untoward medical occurrence in a patient or clinical investigation 
patient administered a pharmaceutical product and which does not necessarily have 
a causal relationship with this treatment. An AE can therefore be any unfavorable 
and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of a medicinal product, whether or not 
related to the medicinal product, e.g.: 
 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
18
 
any new diagnosis 
 
any symptom that requires medical clarification or leads to in-patient 
admission (surgery or accident) 
 
any suspected adverse drug reaction (ADR) 
 
any symptom that appears on the patient’s medical records 
 
any event related in time with the application of the study medication and 
affecting the health of the patient (including laboratory value changes) 
Serious Adverse Events (SAE) 
A serious adverse event (experience) is any untoward medical occurrence that at 
any dose: 
 
results in death 
 
is life-threatening 
 
requires inpatient hospitalization or prolongation of existing hospitalization  
 
results in persistent or significant disability/incapacity 
 
Non-serious adverse events are all AEs that do not fall into any of the above 
categories. 
Expected Adverse Events (i.e. complications of procedures; definitions 
included): 
 Wound infection:  redness or purulence at the IPAA incision that required 
opening of the wound and or treatment with antibiotics 
 Abdominal or pelvic abscess:  abnormal abdominal or pelvic fluid collection 
detected by CT or other imaging in a patient with clinical evidence of infection  
 IPAA radiologic leak:  free or contained extravasation of luminal contrast from 
the IPAA in a patient without clinical signs of IPAA leak  
 IPAA clinical leak:  free or contained extravasation of luminal contrast from the 
IPAA in a patient with clinical signs of IPAA leak  
 IPAA stenosis:  more than a simple web that can be treated by digitation 
 Small bowel obstruction (SBO):  radiologic confirmed in a patient with clinical 
signs of SBO 
 Ileus:  inability to tolerate normal oral intake by 72 hours after IPAA or ostomy 
reversal and/or radiologically confirmed in a patient with clinical signs of ileus 
 Venous Thromboembolism:  new diagnosis of upper or lower extremity of 
mesenteric vein VTE or pulmonary embolism after IPAA or ostomy reversal 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
19
 Lung or heart-related complications:  include new diagnosis of cardiac 
arrhythmia, coronary artery disease, congestive heart failure, pneumonia, 
pneumonitis after IPAA or ostomy reversal 
 Hemorrhage requiring transfusion:  pRBC administered after IPAA or ostomy 
reversal 
 High output ileostomy:  Regular use of antiperistaltic drugs required to control 
ileostomy output volume 
 Peristomal skin irritation:  irritation of the peristomal skin that resulted in pain, 
interference with activities of daily living (ADL), or unplanned treatments 
 Peristomal infection:  peristomal cellulitis or abscess requiring incision and 
drainage or unplanned ostomy surgery or antibiotic therapy 
 Ileostomy prolapse:  ileostomy prolapse that interferes with ileostomy pouching 
and/or ADL or requires surgical treatment 
 Ileostomy stenosis:  ileostomy stenosis that causes ileostomy dysfunction 
and/or interferes with ADL or requires surgical treatment 
 Ileostomy revision necessary:  unplanned ileostomy surgical treatment 
required 
 Ileostomy leakage:  persistent or recurrent ileostomy appliance leakage that 
interferes with ADL and requires more than ordinary measure to control 
 Ileostomy dysfunction:  dysfunction of the ileostomy that causes extraordinary 
problems with output, pouching, intestinal blockages, or otherwise interferes 
with ADL more than is usual and expected. 
 Reoperation:  any unplanned reoperation within 6 months of IPAA surgery 
 Readmission:  Any unplanned hospital readmission within 6 months of IPAA 
surgery 
 Postoperative complication occurrence will be assessed via medical record 
review, discussion with study surgeon, other care givers, and study patient 
and recorded (CRF-6) at an interval of every 1 month until 6 months after 
randomization.   Postoperative complication severity will be scored according 
to the Clavien-Dindo (CD) classification of surgical complications (Dindo, 
2004, Table)  The Comprehensive Complication Index will be calculated for 
each patient at 6 months after randomization.   
 
6 DOCUMENTATION AND REPORTING OF ADVERSE EVENTS 
All adverse events will be treated at the discretion of each individual center. All 
adverse events will be followed to resolution or until determined to be permanent. 
Adverse events will be graded using the definitions below: 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
20
 
Grade 1:  Mild asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
 
Grade 2:  Moderate, minimal, local or noninvasive symptoms with intervention 
indicated; limiting age-appropriate instrumental ADLs (Activities of Daily Living). 
 
Grade 3:  Severe or medically significant symptoms but not immediately life-
threatening; Hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care ADL. 
 
Grade 4:  Life-threatening consequences; urgent intervention indicated. 
 
Grade 5:  Death related to AE. 
 
Serious Adverse Events: All information regarding SAEs will be collected and 
recorded on a specific SAE form. To ensure patient safety, each SAE must also be 
reported to the University of Colorado, within 24 hours of learning of its occurrence. 
 
An SAE is defined by an undesirable sign, symptom or medical condition defined as 
an event which is: 
1. 
Fatal or life-threatening 
2. 
Results in persistent or significant disability/incapacity 
3. 
Requires inpatient hospitalization 
4. 
Constitutes a congenital anomaly/birth defect, 
5. 
Is medically significant, i.e., defined as an event that jeopardizes the patient 
or may require medical or surgical intervention to prevent one of the outcomes listed 
above. 
 
The following has to be documented for each AE: 
 Nature of the event 
 Time of onset: date, time 
 Concomitant treatment: product (generic name), indication, dosage, dosage 
interval, presentation, mode of administration, administration regimen 
 Duration of the AE 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
21
 Severity 
 Seriousness 
 Causality 
 Outcome 
 
Severity 
The severity is evaluated as follows: 
1. Mild: 
- event/symptom does not interfere with normal daily activities 
2. Moderate: 
- event/symptom interferes with normal daily activities 
3. Severe: 
- event/symptom prevents normal daily activities 
Causality 
The relationship between an AE and the research is classified by the following: 
Certain 
A clinical event, including laboratory test abnormality, is occurring in a plausible time 
relationship to the research, and which concurrent disease or other drugs or 
chemicals cannot explain.  
Probable/Likely 
A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to the research , unlikely to be attributed to concurrent disease or other 
drugs or chemicals, and which follows a clinically reasonable response. Possible  
A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to the research, but which could also be explained by concurrent disease 
or other drugs or chemicals.  Unlikely  
A clinical event, including laboratory test abnormality, with a temporal relationship to 
the research which makes a causal relationship improbable, and in which other 
drugs, chemicals or underlying disease provide plausible explanations. 
Conditional/Unclassified 
A clinical event, including laboratory test abnormality, reported as an adverse 
reaction, about which more data are essential for a proper assessment or the 
additional data are under examination. 
Not assessable / Unclassifiable 
A report suggesting an adverse reaction, which cannot be judged because 
information is insufficient or contradictory, and which cannot be supplemented or 
verified. 
 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
22
 
Not related 
There is sufficient information available to show that the eventis unrelated to the 
research.   
 
The course and outcome of the adverse event will be commented on as follows: 
1) 
Recovered without sequelae 
2) 
Not yet recovered 
3) 
Recovered with sequelae 
4) 
Fatal 
Documentation and Reporting of Serious Adverse Events 
On enrolment in the study, the patients will be instructed to contact the investigator 
if a serious or unexpected AE occurs, so that appropriate measures can be taken. 
Any SAE (including death, irrespective of the cause) occurring during or for 
up to 14 days after the end of the study must be reported without delay, i.e. 
within five days, by telephone and by fax to the principal investigator of the 
study organization or his designee, irrespective of its relationship with the 
research(minimum information required: investigator’s name/study center, 
patient number, patient initials, date of first dose, date of last dose, date of 
event, description of event, causality assessment, and countermeasures). 
 
Address: 
Dept. of Surgery 
12631 E. 17th Ave 
Aurora, CO 80045 
Principal investigator 
Jon Vogel, MD 
Phone:  303 724-2728 
 
Fax: 303 724-2733 
 
A specific AE documentation form will be provided to the investigators (see 
appendix). In case of an SAE, this should be completed by the physician as an 
initial report, and sent (via fax) to the principal investigator. The report must contain 
a detailed description of the symptoms observed and the concomitant treatment 
administered. Furthermore, the investigator must comment on a possible causative 
relationship between the AE and the trial medication. Each SAE must be followed 
until it is resolved or can be explained satisfactorily. 
In accordance with drug safety and national requirements, the study PI will inform 
the Data and Safety Monitoring Board (DSMB) of the study and will make sure that 
the involved persons will obtain adequate information. Also the local principal 
investigator will inform the local Ethics Committee.  

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
23
The following instructions must be heeded: 
In the case of an intolerable SAE, the patient must, at the decision of the 
investigator, be withdrawn from the clinical trial, and symptomatic treatment must be 
administered. The measures taken must be recorded on the electronic CRF. 
In accordance with local legislation, the investigators will submit copies of the final 
SAE-report to the Regulatory Authorities concerned, if necessary. 
 
7 WITHDRAWAL OR STOP OF STUDY CRITERIA 
Criteria in individual cases 
Any patient can withdraw from the study at any time without personal disadvantages 
and without having to give a reason. The time of withdrawal, the results available up 
to that time, and, if known, the reason for withdrawal must be documented on the 
electronic CRF.  
The investigator can also discontinue the study after considering the risk-to-benefit 
ratio, if he/she no longer considers the further participation of the patient justifiable. 
The date of and the primary reason for the withdrawal as well as the observations 
available at the time of withdrawal are to be documented on the electronic CRF. 
Reasons leading to the withdrawal of a patient can include the following (primary 
reason must be determined): 
 inclusion criterion not fulfilled or exclusion criterion fulfilled; coming to knowledge 
after recruitment  
 patient’s request 
 technical or logistical reasons (e.g. a change in place of residence, not referred 
by family physician, etc.)  
 other reasons (noting reason) 
 
Criteria for the termination of the whole study 
If serious safety concerns arise, the coordinating investigator can terminate or 
interrupt the study by agreement with the sponsor. If new information on the risk-to-
benefit ratio of the treatment methods used in the study is obtained in the meantime, 
the coordinating investigator reserves the right to interrupt or terminate the project 
by agreement with the sponsor. Premature termination is also possible if the 
coordinating investigator, or the investigators and the sponsor if patient recruitment 
is insufficient and cannot be expedited by appropriate measures.  
 
 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
24
 
8 DATA SAFETY MONITORING  
Data Safety Management Board:  An independent Data and Safety Monitoring 
Board (DSMB), comprised of 2 independent surgeons and 1 biostatistician, has 
been established and will meet at the start of the study and at months 6 and 12 after 
enrollment begins.  The chairman and site investigators will be masked to study 
outcomes during the course of the trial.  Only the study biostatistician and DSMB 
members will have access to the study outcomes for monitoring purposes during the 
course of the study.   
 
Stopping Endpoints:   At their first meeting, the DSMB will decide how they wish to 
monitor the study.  Typically, a DSMB will monitor all aspects of a study to ensure 
its scientific integrity, including patient screening and accrual, follow up, 
performance of individual centers, data acquisition and quality issues, adverse 
events, and outcomes.  At the first meeting, we will also determine their desire in 
establishing formalized stopping rules.  Any data presented by treatment group at 
the DSMB meeting will be blinded with regard to the identity of the comparison 
groups, and participating investigators (except for the study biostatistician) will not 
see any data broken down by treatment group during the course of the trial. 
 
9 RANDOMIZATION, DATA MANAGEMENT AND DATA 
MONITORING 
The randomization of the patients and the processing and analysis of the data will 
be carried out by the lead study biostatistician (William Henderson, PhD) at 
University of Colorado.  The randomization will be stratified by study site.  Within 
each site, randomly selected block sizes of 2, 4, or 6 will be used so that the site 
investigators cannot predict beforehand the group to which the patient will be 
randomized. 
Data collection will be performed using REDCap (Research Electronic Data 
Capture).  REDCap is a secure web application for building and managing online 
surveys and databases.  The software is available at no cost for REDCap 
Consortium Partners.  The building of an online survey or database and the 
inputting of data can be done anywhere in the world over a secure web connection 
with authentication and data logging.  The REDCap surveys and databases can be 
used by researchers from multiple sites and institutions.  Confidentiality will be 
protected.  REDCap is considered “Part 11 capable”, meaning that the software has 
all the required features for compliance. 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
25
We have built a REDCap database for this study using 8 forms per patient.  These 
will include Form 1, Screening;  Form 2, Pre-IPAA Data; Form 3, IPAA operative 
Details,; Form 4, IPAA Assessment;  Form 5, ostomy reversal details;  Form 6,  
Complications;  Form 7 – Functional Outcome & SF-12;  Form 8, Adverse Events.   
Study data for this study will be collected and stored using electronic records.  Data 
captured will be entered in real time at each clinical site using web forms developed 
to replicate paper case report forms.  All data will be created, modified, maintained, 
archived, retrieved and distributed by a computer system.  The use of electronic 
records will increase the speed of data collection and exchange.  This will reduce 
the manpower necessary to perform double-data entry from paper forms and 
transcription error.  In addition, electronic records permit economical storage of 
study data and ease of accessibility and analysis. Data management and data 
quality systems will be built into the system.   
Data quality using electronic records will ensure that data are attributable, legible, 
contemporaneous and original.   
The biostatistics team at the University of Colorado will track the data collection, 
provide data security, control for confidentiality of study data, maintain computer 
backups to protect data until study closure and archive study data according to FDA 
requirements (21 CFR 11).  Electronic signatures will be linked to each entry.   
All computer systems and programs will be password protected, and all electronic 
communications of study and other confidential information will be encrypted. 
Personnel at the CGIBD have extensive training and experience using electronic 
data systems.  Good computer security practice (restricting physical access to 
machines, prohibition of password sharing, and logging off computers after work 
hours or when away from the machine) will be required of all study personnel.  
Only authorized persons are authorized for data entry and access.  Data security 
systems require password protected identification codes for data entry and provide 
protection against data manipulation.  The database is located on a server protected 
by firewalls.  Access to the database server will not be allowed by users on 
computers outside of the firewall-protected zone.  Virus protection software is 
installed on each study machine.  System access to computer systems will be 
audited.  Redundant backups and off-site backup storage will allow for quick 
restoration of data in the unlikely event that a hardware failure, disaster, or security 
breach should occur.  Servers and backups will be located in a secured location 
with access limited to authorized personnel. 
Data cleaning will include range and edit checks, cross form edit checks, query 
generating and tracking and periodic data status reports.  Any data errors or 
inconsistencies detected 
after data 
entry 
will be 
automatically 
tracked, 
communicated and resolved using a web-based application.  An audit trail of all data 
changes over the life of the study will be maintained.  All study raw data, forms, 
documents, software programs, software applications and computer data files will 
be indexed and archived routinely.  Strict version control of documents and software 
applications will be instituted.  Retention of study documentation after study 
completion will be seven years after closure with the IRB. Standardized study 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
26
management reports will be generated monthly during the recruitment phase of the 
study.  These reports will be used to track study progress including patient 
enrolment, randomization, compliance, patient status changes, and study events.  
The data will be reported for each Study Center individually and summarized for the 
study as a whole.  A report will also be generated for the DSMB meeting.  This 
report will include additional information on clinical events and adverse events that 
is coded by blinded treatment group.  Other than the study statistician and statistical 
analyst, no study personnel will see this report.  
10 STATISTICAL CONSIDERATIONS 
Sample Size Calculation 
The developers of the CCI consider a 10-point difference in their 0 to 100 morbidity 
scale to be clinically meaningful; it reflects a 1-grade difference in the established 
Clavien-Dindo classification of postoperative complications (Slankamenac, 2014; 
Clavien, 2009).   They also report a standard deviation of the CCI of 20-22 in two 
surgical trials.  Assuming 80% power and an α = 0.05 level of significance, our trial 
would need about 63-76 patients per group, or a total of 126-152 patients to 
complete both phases of the trial.  It is anticipated that up to 600 patients will be 
required for phase 1 due to the expected ≤ 75% drop out of phase 1 patients who 
are not eligible for phase 2.   
Statistical analyses 
A Consort Diagram will be used to account for all patients screened for inclusion in 
the trial; those who were excluded and included and reasons for exclusion; those 
who were randomized; and those who were followed at each time point or who were 
lost to follow-up.  The primary analysis will be by intention-to-treat, meaning that the 
patients will be analyzed by the group to which they were randomized.  This means 
that patients randomized to the short interval closure group who have postoperative 
complications that delay closure will still be analyzed in the group to which they 
were randomized.  Secondary analyses will be done per-protocol (analyzing 
patients who followed the protocol), and as-treated (analyzing patients by the 
treatment they actually received). 
Patient baseline characteristics will be compared between the early and late closure 
groups using a chi-square test for categorical variables and a t-test for independent 
samples for normal continuous variables or a Wilcoxon two sample ranks test for 
non-normal continuous variables. 
Complications will be reported using the Clavien-Dindo classification.  Perioperative 
details in the two groups will be compared using the same methods as were used 
for comparing the patient baseline characteristics. 
The primary analysis will be comparing Comprehensive Complication index and 
overall complication rates up to 6 months postoperatively between the two 
randomized groups using a generalized linear model with a log-link function with 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
27
group (short vs. long interval closure) and hospital as the independent variables.  
We will also include any patient baseline characteristics that remained unbalanced 
in spite of randomization.  Secondary analyses will include a comparison of mean 
number of complications per patient using a zero-inflated Poisson model, and a 
comparison of severe complications (Clavien-Dindo Grade IIIa or higher) using the 
same methods as were used for the primary analysis.  We will also compare the 
mean number of stoma related complications using a zero-inflated Poisson model.  
Since the quality of life scales are continuous variables measured over time, we will 
compare the early vs. late closure groups for these outcomes using linear mixed 
models. 
 
DSMB interim analyses and early stopping rules for interim 
analyses 
At their first meeting, the DSMB will decide how they wish to monitor the study.  
Typically, a DSMB will monitor all aspects of a study to ensure its scientific integrity, 
including patient screening and accrual, follow up, performance of individual 
centers, data acquisition and quality issues, adverse events, and outcomes.  At the 
first meeting, we will also determine their desire in establishing formalized stopping 
rules.  Any data presented by treatment group at the DSMB meeting will be blinded 
with regard to the identity of the comparison groups, and participating investigators 
(except for the study biostatistician) will not see any data broken down by treatment 
group during the course of the trial. 
 
 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
28
 
11 REFERENCES 
1. Dindo D, Demartines N, Clavien PA.  Classification of surgical complications:  
a new proposal with evaluation in a cohort of 6336 patients and results of a 
survey.  Ann Surg 2004; 240: 205-213. 
2. Danielsen AK, Correa-Marinez A, Angenete E, Skullmann S, Haglind E, 
Rosenberg J, Scandinavian Outcomes Research Group.  Early closure of 
temporary ileostomy—the EASY trial:  protocol for a randomized controlled 
trial.  BMJ Open 2011; 1: e000162. 
3. Danielsen AK, Park J, Jansen JE, Bock D, Skullmann S, Weden A, Correa-
Marinez A, Haglind E, Angenete E, Rosenberg J.  Early closure of a 
temporary ileostomy in patients with rectal cancer.  A multicenter randomized 
controlled trial.  Ann Surg 2017; 265: 284-290. 
4. Alves A, Panis Y, Lelong B, Dousset B, Benoist S, Vicaut E.  Randomized 
clinical trial of early versus delayed temporary stoma closure after 
proctectomy.  Br J Surg 2008; 95: 693-698. 
5. Slankamenac K, Graf R, Puhan MA, Clavien PA.  Perception of surgical 
complications among patients, nurses and physicians: a prospective cross-
sectional survey. Patient Saf Surg. 2011 Nov 22;5(1):30 
6. Slankamenac K, Graf R, Barkun J, Puhan MA, Clavien PA. The 
comprehensive complication index: a novel continuous scale to measure 
surgical morbidity. Ann Surg. 2013 Jul;258(1):1-7 
7. Slankamenac K, Nederlof N, Pessaux P, de Jonge J, Wijnhoven BP, 
Breitenstein S, Oberkofler CE, Graf R, Puhan MA, Clavien PA.  The 
comprehensive complication index: a novel and more sensitive endpoint for 
assessing outcome and reducing sample size in randomized controlled trials.  
Ann Surg. 2014 Nov;260(5):757-62 
8. Farouk R, Pemberton JH, Wolff BG, Dozois RR, Browning S, Larson D.  
Functional outcomes after ileal pouch-anal anastomosis for chronic ulcerative 
colitis. Ann Surg. 2000 Jun;231(6):919-26. 
9. Delaney CP, Fazio VW, Remzi FH, Hammel J, Church JM, Hull TL, Senagore 
AJ, Strong SA, Lavery IC. Prospective, age-related analysis of surgical 
results, functional outcome, and quality of life after ileal pouch-anal 
anastomosis.  Ann Surg.2003; 238(2):221-8 
10. Yamada A, Komaki Y, Patel, N, et al.  Risk of postoperative complications 
among inflammatory bowel disease patients treated preoperatively with 
vedolizumab.  Am J Gastroenterol. 2017;112(9):1423-1429. 
 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
29
11. Lau C, Dubinsky M, Melmed G, Vasiliauskas E, Berel D, McGovern D, Ippoliti 
A, Shih D, Targan S, Fleshner P. The impact of preoperative serum anti-
TNFα therapy levels on early postoperative outcomes in inflammatory bowel 
disease surgery. Ann Surg. 2015;261(3):487-96. 
12. Nørgård BM, Nielsen J, Qvist N, Gradel KO, de Muckadell OB, Kjeldsen J. 
Pre-operative use of anti-TNF-α agents and the risk of post-operative 
complications in patients with ulcerative colitis - a nationwide cohort study. 
Aliment Pharmacol Ther. 2012 Jun;35(11):1301-9 
13. Kulaylat AS, Kulaylat AN, Schaefer EW, Tinsley A, Williams E, Koltun W, 
Hollenbeak CS, Messaris E. Association of Preoperative Anti-Tumor 
Necrosis Factor Therapy With Adverse Postoperative Outcomes in Patients 
Undergoing Abdominal Surgery for Ulcerative Colitis. JAMA Surg. 2017 Aug 
16;152(8):e171538 
 
Appendix 
 
Table:  Clavien-Dindo Classification (From Reference #1) 
 
 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
30
Illustrations:  
-------------------------------------------------------------------------------------------------------- 
2-stage IPAA with (loop) ileostomy 
 

 
Timeline study visits 
Procedure 
Timing 
Location 
and/or 
individual 
responsible 
Inclusion/exclusion 
criteria 
assessment 
PHASE 
1: 
 
During 
IPAA 
preoperative assessment 
Surgical 
outpatient 
clinic 
/ 
Surgeon or trial assistant 
Informed Consent #1:  obtained 
from patients who meet initial 
inclusion and exclusion criteria 
 
 
Case 
Report 
Form 
(CRF)-1 
completion (Screening) 
PHASE 
1: 
 
During 
IPAA 
preoperative assessment 
Surgical 
outpatient 
clinic 
/  
Surgeon or trial assistant 
Case 
Report 
Form 
(CRF)-2 
completion (Pre-IPAA details) 
PHASE 1:  Within 2 days of IPAA 
REDCap application / Surgeon or 
trial assistant 
IPAA surgery 
PHASE 1:  At discretion of 
patient and surgeon and within 
30 days of inclusion/exclusion 
criteria assessment 
Study site operating room / 
surgeon 
Case 
Report 
Form 
(CRF)-3 
completion (IPAA surgery details) 
PHASE 1:  Within 2 days of IPAA 
surgery 
REDCap application / surgeon or 
assistant 
Post-IPAA clinical assessment 
PHASE 1:  Day 5 to 12 after 
IPAA 
Study site inpatient setting / 
Surgeon  
Exclusion 
of 
potential 
study 
patients 
judged 
not 
clinically 
suitable for trial entry.  Case 
Report Form (CRF)-4  (IPAA 
Assessment) 
PHASE 1:  Day 5 to 12 after 
IPAA 
REDCap application / Study site 
inpatient setting / Surgeon 
Informed 
Consent 
#2 
– 
obtained 
only 
from 
potential 
study patients who are clinically 
suitable 
for 
early 
ileostomy 
reversal  
PHASE 2:  Day 5 to 12 after 
IPAA, 
after 
IPAA 
clinical 
assessment 
Study site inpatient setting / 
Surgeon 
Radiologic imaging assessment 
of the IPAA 
PHASE 2:  Day 5 to 12 days after 
IPAA 
Study site radiology suite 
Case 
Report 
Form 
(CRF)-4 
completion (IPAA Assessment) - 
finish 
PHASE 2:  Day 5 to 12 after 
IPAA, after IPAA radiological 
assessment 
REDCap application / Study site 
inpatient setting / Surgeon 
Randomization 
- 
of 
study 
patients who are radiologically 
suitable 
for 
early 
ileostomy 
closure 
PHASE 2:  Day 5 to 12 days after 
IPAA 
Study site trial coordinator office / 
trial assistant 
Ileostomy Closure 
PHASE 2:  Experimental Arm:  
7 to 12 days after IPAA surgery 
Control Arm:  ≥ 8 weeks after 
IPAA surgery 
Study site operating room 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
32
Case 
Report 
Form 
(CRF)-5 
completion 
(ostomy 
reversal 
details) 
PHASE 2:  Within 2 days of 
ostomy closure 
REDCap application / surgeon or 
assistant 
Outcome Assessment #1- Case 
Report 
Form 
(CRF)-6 
(complications) 
PHASE 2:  0-1 month after 
randomization. 
REDCap application / surgeon or 
assistant 
Outcome Assessment #2- Case 
Report 
Form 
(CRF)-6 
(complications) 
PHASE 2:  1-2 months after 
randomization.  
REDCap application / surgeon or 
assistant 
Outcome Assessment #3- Case 
Report 
Form 
(CRF)-6 
(complications) 
PHASE 2:  2-3 months after 
randomization. 
REDCap application / surgeon or 
assistant 
Outcome Assessment #4- Case 
Report 
Form 
(CRF)-6 
(complications) 
PHASE 2:  3-4 months after 
randomization. 
REDCap application / surgeon or 
assistant 
Outcome Assessment #5- Case 
Report 
Form 
(CRF)-6 
(complications) 
PHASE 2:  4-5 months after 
randomization. 
REDCap application / surgeon or 
assistant 
Outcome Assessment #6- Case 
Report 
Form 
(CRF)-6 
(complications) 
PHASE 2:  5-6 months after 
randomization. 
REDCap application / surgeon or 
assistant 
Functional outcome and SF-12 
Case 
Report 
Form 
(CRF)-7 
completion (Function & SF-12) 
PHASE 2:  At 6 months after 
randomization 
REDCap application / surgeon or 
assistant 
Case 
Report 
Form 
(CRF)-8 
completion (Adverse Events) 
PHASE 2:  Assessed on a daily 
interval, during hospitalization(s), 
after IPAA and ostomy reversal 
surgery and then reassessed at 
1-2 month 
intervals, 
until 6 
months after IPAA. 
REDCap application / surgeon or 
assistant 
 

Clinical Adverse Event Reporting Form 
 
Short versus long interval to loop ileostomy reversal after ileal pouch surgery 
in patients with ulcerative colitis (SLIRPS) trial 
A randomized, prospective trial investigating the timing of diverting ileostomy closure 
after ileal j-pouch surgery.   
Event ID: ________ Study Center: _________ Study ID: ___________ 
Event Name:______________________________________________ 
 
DOB: __ __/ __ __/ __ __ __ __  Gender: ______ 
Race: _______ 
         mm        dd          yyyy 
Name of MD Reporting Event? 
______________________________ 
 
 
Date of Medical Review 
 __ __/ __ __/ __ __ __ __ 
 
     mm   dd        yyyy 
Is this a Serious Adverse Event (SAE)?  
    Yes 
     No 
 
 
Indicate all classifications(s) applicable 
    Death 
    Life threatening 
     Disability 
     Congenital anomaly/birth defect 
     Hospitalization - Initial 
     Hospitalization - Prolongation 
     Other 
 
 
Specify Other 
 
 
 
Relationship/Causality (likelihood that 
study agent caused the event) 
     Not related 
     Probably not related 
     Possibly related 
     Related 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
34
Is the event Expected?  
 
Is the event Unexpected? 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
35
 
 
 
MD Narrative: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Measures at the onset of adverse 
event 
    None 
   Surgical Procedure 
   Treatment with medication
     Other 
 
Specify Other: 
 
 
 
Outcome of event (sequelae are 
defined as conditions following and 
resulting from event)  
     Recovered without sequelae 
     Recovered with sequelae 
     Not yet recovered 
     Died 
 
Signature of Study Center MD 
 
 
 
 
__________________________________ 
Date Form Completed 
__ __/ __ __/ __ __ __ __ 
 
  
 
 
 
 
    mm   dd          yyyy 
 

Timing of Ileostomy Closure after Ileal Pouch Surgery 
 
36
 Lead Study Principal Investigator assessment: 
 
Soes this event suggests that the research places subjects or others at greater risk of physical 
of psychological harm than was previously known or recognized? 
 
Yes                          No 
Within 5 days of knowledge of event please email: 
 
Jon.vogel@CUAnschutz.edu 
Tracey.MacDermott@CUAnschutz.edu