Prospective Randomized Controlled Trial Investigating Commencement of Low Residue Diet Versus Clear Liquids on Postoperative Zero Following Elective Colorectal Surgery
Phase: NA
Conditions: Nausea/Vomiting
Sponsor: Cedars-Sinai Medical Center

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PROSPECTIVE RANDOMIZED TRIAL OF IMMEDIATE POSTOPERATIVE USE OF A 
REGULAR DIET VERSUS CLEAR LIQUIDS IN ELECTIVE COLORECTAL SURGERY. 
 
 
 
Protocol Number: 
 
07 10 July 2017, Version 1 
 
 
Lead Investigator: 
 
Phillip Fleshner, MD 
 
 
Division of Colorectal Surgery 
Cedars-Sinai Medical Center 
 
 

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BACKGROUND. Offering patients, a low residue diet on the first postoperative day (POD1) 
after colorectal surgery is safe and improves surgical outcomes and postoperative hospital stay 
(Lau C, Phillips E, Bresee C, Fleshner P. Early use of low solid is superior to clear liquid diet after 
elective colorectal surgery. Ann Surg 2014; 260:641-649). We have recently demonstrated the 
feasibility and safety of the immediate use of a regular diet after elective colorectal surgery 
(Chough I, Zaghiyan K, Ovsepyan G, Fleshner P. A feasibility and safety study of the immediate 
use of a regular diet after elective colorectal surgery. Poster, Annual Meeting of the Southern 
California Chapter of the American College of Surgeons, Jan 2017 and Chough I, Zaghiyan K, 
Ovsepyan G, Fleshner P. Prospective study of the feasibility and safety of the immediate use of a 
regular diet after elective colorectal surgery. ePoster American Society of Colorectal Surgeons, 
June 2017). The purpose of this study is to prospectively evaluate whether providing a patient a 
solid diet from postoperative day zero is superior to clear liquids. The primary endpoint measured 
will be patient tolerability, as evidenced by absence of vomiting. The secondary endpoints 
measured will be duration of supplemental intravenous hydration needed, length of hospital stay 
and postoperative complications, and intestinal rate measured by Abstats (Gi Logic, Pasadena, 
CA).  
 
AbStats™ (GI Logic; Pasadena, CA) is an FDA cleared wearable gastrointestinal biosensor 
system for functional assessment of the gastrointestinal tract. The device has been tested and 
validated for monitoring of gastrointestinal recovery after colorectal surgery (Kaneshiro et al. 
Postoperative Gastrointestinal Telemetry with an Acoustic Biosensor Predicts Ileus vs. Uneventful 
GI Recovery. J Gastrointest Surg 2016; 20:132-9; Spiegel et al. Validation of an Acoustic 
Gastrointestinal Surveillance Biosensor for Postoperative Ileus. J Gastrointest Surg. 2014; 
10:1795-803). In these prior studies, Abstats has predicted postoperative ileus with a slower 
median intestinal rate 3.01/min compared with patients not developing ileus (median intestinal rate 
4.46/min). However, in these studies, advancement of diet was not standardized and many patients 
were maintained NPO until return of flatus. A secondary aim of this study will be to compare 
intestinal rate measured by Abstats™ in patients offered immediate solid versus clear liquids after 
colorectal surgery to determine if Abstats™ can predict intolerance to feeding early on.  
 
PROTOCOL 
 
Protocol Title: 
 
Prospective randomized controlled trial investigating commencement of 
low residue diet versus clear liquids on postoperative zero following 
elective colorectal surgery, with regards to patient tolerability, incidence 
of nausea and/or vomiting, and postoperative length of hospitalization 
stay.  
 
Study Rationale 
The purpose of this study is to evaluate whether giving a low residue 
diet immediately after elective colorectal surgery is superior to clear 
liquids with regards to patient tolerability in an elective colorectal 
surgery patient.  Patient tolerability is evidenced by absence of 
vomiting.  
 

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Study Population: 
Based on current literature, the incidence of postoperative nausea and 
vomiting varies widely and can reach up to 40% in abdominal surgery 
patients. Thus, patient tolerability to postoperative enteral feeds is taken 
as 60%.  
This is a superiority trial: Group I is the clear liquids group and patient 
tolerability in this group is taken to be 60%.  Group II is the low residue 
diet group. Group II is assumed to be superior to group I with respect to 
patient tolerability.  
Group sample sizes are taken to be 50 in group one and 50 in group two, 
thus achieving an 80% power to detect a difference between the group 
proportions of 0.2451. 
The proportion in group one is assumed to be 0.6000 under the null 
hypothesis and 0.8451 under the alternative hypothesis.  
The proportion in group two is 0.6000. The test statistic used is the two-
sided Z test with pooled variance. 
The significance level of the test was targeted at 0.0500. The 
significance level actually achieved by this design is 0.0524. 
 
Hypothesis 
The primary hypothesis is that the incidence of postoperative ileus is not 
affected by the consistency of enteral diet given, and patients who are 
placed on low residue diet from postoperative zero do not have an 
increased risk of postoperative nausea and/or vomiting as compared to 
patients who are placed on clear liquids.  
The null hypothesis in this superiority trial design is that both group I 
(clear liquids group) and group II (low residue diet group) are equally 
tolerated by patients on postoperative day one following elective 
colorectal surgery.  
The alternative hypothesis is that both groups differ, and group II (low 
residue diet group) is superior to group I (clear liquids group) with 
regards to patient tolerability.  
Study Design: 
Single-center, prospective, randomized trial.   
Intestinal Telemetry 
Abstats™ consists of a disposable plastic device embedded with a 
microphone that adheres to the abdominal wall and connects to a 
computer measuring acoustic event rates. The monitor will be placed on 
the patient’s abdomen 30 minutes prior to surgery in the preoperative 
holding area to obtain baseline intestinal rate. The monitor will be 
removed prior to surgery and replaced by the surgical team in the 
operating room and maintained until postoperative day 3. Daily 
intestinal rate will be calculated as mean and median acoustic events per 
minute. The raw data will be analyzed by an investigator blinded to the 
clinical data.  Intestinal rates of patients offered immediate solid feeds 
will be compared with those offered clear feeds. In addition, patients not 
tolerating or consuming early solid meal will be compared with those 
who do to identify whether Abstat™ can be an early predictor of diet 
intolerance in patients undergoing colorectal surgery.  

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Primary Efficacy 
Endpoint: 
Patient tolerability, as evidenced by development of vomiting on 
postoperative day two. 
Secondary 
Endpoints: 
1. Whether ordered diet was consumed and % consumption on POD0 
2. Time to flatus. 
3. Time to first bowel movement 
2.  Length of postoperative stay. 
3. Quality of life measures, recorded by self-administered questionnaire.   
    (Please see appendix A for the questionnaire.) 
4. Duration of supplemental intravenous hydration.  
5. Need for insertion of nasogastric tube. 
6. Postoperative complications, including surgical site infections. 
7. GI motility patterns as assessed by ABStats 
8. Composite of patient reported nausea, vomiting, abdominal distention 
or bloating, belching, heartburn, eructation, gas pain, constipation, 
diarrhea, halitosis, aspiration, pneumonia, regression of feeding to NPO 
or liquid feeds, intraabdominal abscess or anastomotic leak, insertion of 
NG tube, fecal impaction, small bowel obstruction, postoperative use of 
laxative 
Safety Endpoints:  
Enteral feeds or nil by mouth advice the patient would have otherwise 
received. 
Sample size: 
 
The study is powered (α = 0.05, Β = 0.80) to detect a 24.5% difference 
in proportion of patients developing nausea and/or vomiting; 50 patients 
per arm are required.  
 
Interim Analysis 
There will not be an interim analysis. 
Key Inclusion 
Criteria: 
1. Able to freely give written informed consent to participate in the 
study and have signed the Informed Consent Form; 
2. Males or females, >18 years of age inclusive at the time of study 
screening; 
3. American Society of Anesthesiologists (ASA) Class I-III; 
4. Colorectal surgery (open and/or robotic/laparoscopic); 
5. Elective Surgery. 
 
 
 

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Key Exclusion 
Criteria 
1.  Mentally incompetent or unable or unwilling to provide informed 
consent or comply with study procedures. 
2. Children <18 years of age. 
3. Pre-operative clinical diagnosis of intestinal obstruction.  
4. Pre-existing known upper gastrointestinal disorders including hiatus 
hernia, gastroesophageal reflux disease, peptic ulcer disease.  
5. Pre-existing oropharyngeal disorders such as stomatitis, altered taste 
sensations.  
6. Colorectal surgery with concomitant re-sectional surgery of the 
stomach or proximal jejunum (small bowel). 
7. Pregnant patients. 
8. Bedbound or moribund patients. 
9. Pre-existing history of clinical depression.  
10. Epidural analgesia. 
11. Surgical procedures completed after 4pm 
12. Patients taking narcotics prior to elective colorectal surgery 
 
After randomization: 
1. Postoperative diagnosis of intra-abdominal sepsis, including 
anastomotic leaks. 
2. Postoperative complications requiring early reoperation within 
the same hospital stay.  
 
Treatment 
Regimen/ Duration: 
Patients will be assigned into one of two groups:  
Group I - Clear liquids on postoperative day zero immediately upon 
return to the floor and subsequent days’ advancement of enteral diet to 
regular diet is as per discretion of the attending physician.  
Group II - Regular diet from postoperative day zero immediately upon 
return to floor and onwards. 
Three questionnaires assessing quality of life are to be completed by the 
patient, during his/her hospital stay.  
On postoperative day one, a self-administered questionnaire is to be 
completed by the patient. Please see appendix A for the questionnaire 
details.  
The same questionnaire is administered on postoperative day two and 
again on the last day of hospitalization. 

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Treatment Failure/ 
Discontinuation 
Criteria: 
Patients will be discontinued from the trial at any time as a result of any 
other event that in the opinion of the investigator warrants 
discontinuation from the trial. 
Additionally, patients will be excluded after randomization if: 
1. Intraoperative complications require postoperative use of 
nasogastric tube; 
2. Postoperative complications require early re-operation or a 
planned second operation within the same hospital admission. 
3. Prolonged unanticipated need for intravenous opioids beyond 
postoperative day five.  
 
 
 
 
Statistical Analysis Plan 
 
Based on current literature, the incidence of postoperative nausea and vomiting varies widely and 
can reach up to 40% in abdominal surgery patients. Thus, patient tolerability to postoperative 
enteral feeds is taken as 60%.  This is a superiority trial: Group I is the clear liquids group and 
patient tolerability in this group is taken to be 60%.  Group II is the low residue diet group. Group 
II is assumed to be superior to group I with respect to patient tolerability. Group sample sizes are 
taken to be 50 in group one and 50 in group two, thus achieving an 80% power to detect a 
difference between the group proportions of 0.2451. The proportion in group one is assumed to be 
0.6000 under the null hypothesis and 0.8451 under the alternative hypothesis.  The proportion in 
group two is 0.6000. The test statistic used is the two-sided Z test with pooled variance. 
 

 
2.  SCHEDULE OF EVENTS/ DATA COLLECTION  
 
 
 
 
 
 
 
 
Group One: Control arm. Clear liquids 
from postoperative day zero 
 
Visit Number 
Admission  
 
Informed Consent 
✓ 
 
Demographics 
✓ 
 
Height  
✓ 
 
Medical History1 
✓ 
 
Inclusion/ Exclusion Criteria Review 
✓ 
 
Previous /Concomitant Medications 
✓ 
 
Physical Exam2  
✓ 
 
Vital Signs3 
✓ 
 
Body Weight 
✓ 
 
Placement of ABStats7 
✓ 
 
Volume of oral intake on postoperative 
day zero (ml) 
✓ 
 
Adverse Events4  
✓ 
 
Quality of Life Assessment5 
✓ 
 
Hospital Discharge or Early Termination 
Visit6 
✓ 
 

 
 
 
Group Two: Low Residue diet arm.  
Low Residue diet from postoperative day zero. 
 
Visit Number 
Admission  
 
Informed Consent 
✓ 
 
Demographics 
✓ 
 
Height  
✓ 
 
Medical History1 
✓ 
 
Inclusion/ Exclusion Criteria Review 
✓ 
 
Previous /Concomitant Medications 
✓ 
 
Physical Exam2  
✓ 
 
Vital Signs3 
✓ 
 
Body Weight 
✓ 
 
Placement of ABStats7 
✓ 
 
Volume of oral intake on postoperative 
day zero (ml) 
✓ 
 
Adverse Events4  
✓ 
 
Quality of Life Assessment5 
✓ 
 
Hospital Discharge or Early Termination 
Visit6 
✓ 
 

 
 
Both arms:  
Postoperative Data 
 
Open or Laparoscopic 
✓ 
Reason for surgery (benign or cancer, 
palliative intent or curative intent.) 
✓ 
Type of Surgery (LAR, APR, IPAA, 
etc) 
✓ 
ASA Score 
✓ 
Level of anastomosis (less than 5 cm 
from anal verge) 
✓ 
Neoadjuvant chemotherapy 
✓ 
Neoadjuvant radiation therapy 
✓ 
Intraoperative Fluid Volume (mL) 
✓ 
Intraoperative Blood Loss (mL) 
✓ 
Intraoperative and/or Postoperative 
Blood Transfusion 
✓ 
Preoperative Bowel preparation 
✓ 
Diverting stoma 
✓ 
Antibiotic therapy more than 24 hours 
postoperatively 
✓ 
Total 
Hospital 
stay 
Morphine 
equivalent (mg)8 
✓ 
Quality of Life assessment5 
✓ 
ABStats7 motility data 
✓ 

 
1. Medical History information will be collected via medical records at index admission including:  Hypertension, Lung Disease, Diabetes  
2. Comprehensive physical exam information will be collected from medical records at index admission  
3. Vital Signs will be collected form medical records (systolic and diastolic blood pressure, heart rate, respiration rate, and temperature) at 
index admission. 
4. Adverse events (AEs) will be recorded at every visit post screening.  AEs will be followed until resolution. 
5. Quality of Life assessment will be obtained on postoperative day one, postoperative day two and the last day of hospitalization 
(Appendix A) 
6. Early Termination visits are used when a patient withdraws from the study (i.e., prior to hospital discharge). 
7. ABStats motility data using the Acoustic Gastro-Intestinal Surveillance Biosensor (AGIS, GI Logic, Inc. Pasadena CA) 
8.   Morphine equivalent: 7 mg ≈ 1 mg hydromorphone 

 
 
 
 
 
 
 
 
Group I: Clear 
liquids arm 
Group II Low 
residue diet arm 
Clinical Endpoints 
 
 
Patient tolerability:  
- 
Development of nausea 
and/or vomiting from 
postoperative day one, two 
and three.  
 
✓ 
✓ 
Need for insertion of nasogastric 
tube. 
✓ 
✓ 
Return of bowel function; return of 
flatus as surrogate measure.  
✓ 
✓ 
Length of postoperative hospital 
stay. 
✓ 
✓ 
Number of postoperative days on 
supplemental intravenous 
hydration. 
✓ 
✓ 
Surgical site infection 
 
✓ 
✓ 
Other infective complications:  
- 
pneumonia. 
- 
Urinary tract infections. 
✓ 
✓ 
Anastomotic Leak. 
✓ 
✓ 
ABStats motility data7 
✓ 
✓ 

 
 
APPENDIX A  
Quality of Life Assessment Visual Analogue scale. 
 
 
ABDOMINAL PAIN 
Please identify how much abdominal pain you are having by drawing a vertical line across the horizontal line at the location that best 
describes the level of abdominal pain that you are currently experiencing. 
NO PAIN 
 
WORST PAIN 
IMAGINABLE 
 
 
NAUSEA 
Please identify how much nausea you are having by drawing a vertical line across the horizontal line at the location that best describes 
the level of abdominal pain that you are currently experiencing. 
NO NAUSEA 
 
WORST NAUSEA 
IMAGINABLE 
 
 
ABDOMINAL BLOATING 
Please identify how much abdominal bloating you are having by drawing a vertical line across the horizontal line at the location that best 
describes the level of abdominal pain that you are currently experiencing. 
NO BLOATING 
 
WORST BLOATING 
IMAGINABLE 
 
 
FOR STUDY STAFF 
 
I confirm that the above survey was completed by patient __ __ __ on date ___ ___ ___: 
 
Subject ID:__ __ __