Routine Post-Operative Supplemental Nutrition: A Randomized Controlled Trial
Phase: NA
Conditions: Esophageal Cancer
Sponsor: University of Michigan

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Routine post-operative supplemental nutrition: A Randomized Controlled 
Trial 
 
Protocol 01 
 
06/16/2014 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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A. STUDY AIMS 
 
Specific Aim 1: To determine if routine dietary supplementation with enteral tube 
feeding affects recovery and quality of life after esophagectomy.  Medicare rules 
only pay for enteral supplements (tube feeding) if the patient needs alternative 
feeding for greater than 3 months.  Many insurers have adopted these rules, without 
evidence in post-operative patients. 
 We hypothesize that routine post-operative supplementation will enhance 
patients recovery and quality of life, by increasing the time of adequate 
nutrition. 
 
Specific Aim 2: To determine the occurrence of common complications and 
readmissions post-operatively between patients who are routinely discharged with 
tube feeding and those that are not.  If patients are not discharged with tube feeds, 
they must obtain all of their nutrition by mouth, which may be difficult in the early 
post-operative period. 
 We hypothesize that routine use of tube feeding may reduce the occurrence 
of complications.   
 
 
The secondary aims of this randomized clinical trial are: 
 To compare costs of care between groups.  
 To assess how length of stay (LOS) and readmission rates are affected by 
routine use of tube feeding, as well as costs of care. 
 Rates of occurrence of tube feeding or jejunal tube-specific complications 
 
 
B. BACKGROUND AND SIGNIFICANCE 
 
Nutritional support is taking on an increasing focus in peri-operative surgical 
care.  It is particularly important in esophageal resection, which is a high-risk 
operation in a patient population whose pre-operative condition may be reduced 
due to pre-operative chemo- and radio-therapy, as well as dysphagia from the 
cancer.  Post-operatively, patients are routinely cleared to take nutrition by mouth 
once an esophagram is done post-operative day 7 and shows no abnormality.   
Tube feeding should be at goal by day 7, but is discontinued once patients are 
discharged, as long as they are able to eat, i.e., do not have evidence of anastomotic 
leak or other serious complications.  The amount patients are able to eat is 
frequently variable, and is not well recorded prior to or after discharge.  There may 
be a dip in calories consumed, which if severe, will lead to readmission for 

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hydration, failure to thrive, or possibly the development of a post-operative 
complication. 
Currently all patients are discharged with the jejunal feeding tube placed at the 
operation, just in case they are unable to eat post-operatively due to an unforeseen 
complication.  Since many insurers and Medicare require patients to pay for tube 
feeding needed for less than three months (~$800/month and up, plus the services 
of a home health nurse), we do not routinely require patients use the feeding tube 
once discharged.   
For esophagectomy specifically, and upper gastro-intestinal surgery in general, 
there is very limited literature looking at this question.  Small randomized studies 
have not shown a benefit to routine tube feeding, although the numbers were very 
small, ranging from 12 to 70 in each group.  Furthermore, the duration of tube 
feeding averaged 14 days, and even in the groups being fed enterally, were not 
meeting caloric needs in the period studied. 
 
C. STUDY SCHEMA 
 
Patients will be evaluated for surgery by the study surgeons. Patients scheduled to 
undergo an elective esophagectomy and who meet inclusion criteria (See Section 
E.1) will be approached for enrollment.  Written informed consent will be obtained 
from all enrolled patients (see Appendix B). Pre-operative Quality of Life Survey will 
be obtained using the EORTC QLQ-C30 (see attached).  Patients will then be 
randomly assigned to either routine post-operative tube feeding for 1 month, or 
usual practice, tube feeding to continue in the hospital until the patient is taking 
adequate nutrition by mouth at POD#8, or upon discharge.  Since this study cannot 
be blinded, patients that cannot take nutrition by mouth at POD#8, or are tube 
feeding dependent on discharge will not be included in analysis. 
 
Figure 1. Illustrates the study design 
 
 
D. OUTCOME MEASURES 
 
The primary outcome measure for specific aim 1 will be the quality of life and 
patient satisfaction as measured by post-operative survey instruments. 
 
Secondary Outcomes for specific aim 1: 
 Complications following surgery (jejunal tube) 
 Length of stay 
 Costs 
 
The primary outcome for specific aim 2 will be the occurrence of post-operative 
complications such as: atrial fibrillation, delirium, anastomotic leak, pneumonia 
within the 30-day post-operative time frame.   
 

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Secondary Outcomes for specific aim 2: 
 Readmission rates and costs of care. 
  
E. STUDY POPULATION 
 
The study population will consist of patients who are recommended to undergo an 
elective esophagectomy as determined by the surgeon’s evaluation.  
 
E.1.  Inclusion Criteria 
E.1.1 Undergoing an elective esophagectomy 
E.1.2 jejunal feeding tube placed at the time of surgery 
 
E.2.   Exclusion Criteria 
E.2.1 Emergent procedure. 
E.2.2 Less than 18 years of age. 
E.2.3 Inability to provide informed consent or to complete testing or data 
collection. 
E.2.4 Unwillingness to be randomized. 
E.2.5 Tube feeding dependent on discharge. 
 
F. RANDOMIZATION AND MASKING 
 
Randomization envelopes will be created at the start of the study.  Each envelope 
will be opened prior to discharge or at POD#8 if patients are able to take adequate 
nutrition by mouth, to determine if post-operative tube feeding will be continued or 
not.     
 
By consenting to the study, patients agree to continue tube feeding for at least 50% 
of caloric needs for 1 month post-operatively.  Cross-over after randomization will 
be permitted for patient condition, although once randomized, patients will be 
analyzed by the original group. 
 A copy of the signed research consent form must be included in the 
patient’s hospital chart.   
 
G. TREATMENTS 
 
G.1  Standardization of Intervention 
All Procedures: 
1. The participating study surgeons have been trained in and 
regularly perform esophagectomies with jejunostomy tube 
placement.  
2. The supervising study surgeon will be present for key portions of 
the procedure.  Residents or fellows may participate in procedures 
as is standard. 

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3. Patients will undergo standardized preoperative and 
postoperative education. 
4. Patients will undergo standard postoperative care specific to the 
procedure performed, including enteral tube feeding while in the 
hospital until adequate nutrition by mouth is tolerated.  
 
Standardization of Postoperative Care 
Standard protocols will apply while patients are admitted to the hospital.  Once 
discharged from the hospital, patients will be evaluated at a routine 
postoperative appointment.  Attending providers will be blinded as much as 
possible to the discharge tube feeding regimen. 
 
 
H. MEASUREMENT 
 
The assessment instruments that will be used for specific aim 1: 
1. EORTC QLQ-C30, Quality of life in cancer patients 
 
 
The complications assessment instruments that will be used for specific aim 2: 
1. HUM00012731 data collected around the time of operation and post-
operative visit. 
2. Long-term data from HUM00012731 
 
Patients will also be invited to enroll in the “Patient outcomes following 
esophagectomy for benign and malignant disease” HUM00012731, a study in 
which the PI (Philip Carrott) is also a co-investigator.  To minimize patient 
burden, the baseline preoperative assessment and the evaluation for quality of 
life will be performed according to the protocol outlined in HUM00012731.  
Demographics and history forms HUM00012731 will only be administered once 
preoperatively.   This data will then be shared to support the study aims of this 
protocol to minimize patient inconvenience.  In the event, that a patient does not 
wish to be co-enrolled in HUM00012731, the attached forms (EORTC QLQ-C30 
and Demographics and history forms HUM00012731) will be administered by 
the Thoracic Surgery Clinical Coordinator, who will be trained and added to the 
HUM000XXXXX study protocol, at the scheduled time points outlined in Section 
N. 
 
H.1  Primary Outcome Measures:  
 
a. Specific Aim 1 
Quality of life data will be assessed pre-operatively and at the post-
operative visit. 
 
b. Specific Aim 2 

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Occurrence and severity of complications will be recorded by 
HUM00012731.  Patients will be assessed at discharge and return 
visits. Adverse events following surgery (e.g., pneumonia, DVT, PE, 
anastomotic leak, atrial fibrillation, delirium, etc.) will be identified 
prospectively by the study team 
  
 
H.2 Secondary Outcome Measures 
a. Specific Aims 1&2 
 
1. Jejunostomy tube-specific complications will also be 
identified prospectively.  J-tube specific complications include 
infection, bowel obstruction that may require surgical repair, 
discomfort, diarrhea and dumping syndrome. 
 
2. Other outcome measures (length of stay, readmission, etc.) 
 
 
3. Costs will be determined retrospectively by reviewing the 
administrative billing data. 
 
 
 
H.3 Schedule of Measurements 
 
Section N details the schedule of measurements.  Data will be collected 
preoperatively at the initial screening visit, during the perioperative period, 
at the follow-up appointment (2 weeks following discharge), and at 1 month, 
3 months, and 6 months (by telephone or mail). 
 
I. DATA COLLECTION 
 
All data collection following surgery will be performed by research staff 
other than the study surgeon.  This will reduce bias by maintaining masking 
in data collection of outcome measures.  All research staff will be trained and 
certified to perform data collection procedures.  Allowable windows for 
timed evaluations are specified in Section N and include a one-week window 
on each side of the postoperative visit planned at 2-3 weeks. The 
assessments at 1-month, 3-months, and 6-months will take place by mail and 
will not require a visit to the clinical site.  
 
 
I.1  Demographics, Medical History, and Physical Examination 
 
a. History 
i. Age 
ii. Sex 

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iii. Previous medical history  
iv. Prior thoracic procedures 
v. Primary diagnosis 
vi. Previous thoracic chemotherapy or radiation 
vii. Planned procedure 
viii. Comorbidities will be collected using the Charlson Comorbidity 
index collected at baseline 
 
b. Physical Examination 
i. Height 
ii. Weight 
iii. BMI 
 
J. STATISTICAL AND DATA MANAGEMENT CONSIDERATIONS 
 
For the specific aims:   
 
Specific Aim 1: Quality of Life measurements will be compared at 6 months, 
using descriptive statistics.   
 
Specific Aim 2: Calories will be compared between groups.  
 
 
For the secondary aims:  Height and weight will be compared between 
groups at 30 days and 6 months.   
 
 
Sample size justification: This was measured with the possible recruitment 
pool and differences between groups.   
 
 
        
Interim analysis: At 50% recruitment or three years.  
 
 
 
 
Randomization: 
 
This study will randomize eligible patients to receive post-operative tube 
feeding for 1 month or standard post-operative care in a one-to-one fashion. 
Patients will be randomized using a blocked randomization technique in 
order to ensure equal sample sizes across groups.  Lili – is this correct?  The 
study statistician (Lili Zhao) will generate the randomization assignment 
table for the study’s data manager. The investigators will call the data 
manager for the treatment assignment when a patient has been fully 
consented and is determined to be eligible for study enrollment.  

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K. RECRUITMENT 
 
An estimated sample size of XXXXX – insert from Lili evaluable* patients will be 
enrolled over a period of 12-24 months. 
 
* Patients that meet inclusion criteria (see section E.1) and are not excluded 
from participation in the study by the exclusion criteria (see section E.2).  If 
there are patients who drop out of the study or are loss to follow-up, they will be 
replaced to achieve a minimum sample size of XXXXX – insert from Lili evaluable 
patients for specific aims 1 and 2. 
 
ETHICAL CONCERNS- INFORMED CONSENT 
 
It is unclear what kind of difference tube feeding may make post-operatively, 
which is why we are doing this study.  Previous small studies have not shown 
any short-term differences. (see APPENDIX B). 
 
L. DISCUSSION OF POTENTIAL LIMITATIONS IN STUDY DESIGN 
 
A potential pitfall is that patients who consent to the study in the preoperatively, 
may not continue to meet eligibility criteria prior to discharge or at POD#8 
because they are not able to take adequate nutrition by mouth, thus excluding 
the patient from randomization and further participation in the trial.  
 
Another potential pitfall is that patients who randomize to have their tube 
feeding discontinued at discharge may (due to patient condition) require tube 
feedings to be resumed to supplement nutritional needs.  Cross-over after 
randomization will be permitted for patient condition, although once 
randomized, patients will be analyzed by the original group.   
 
Lili, how do we construct randomization schema and power analysis to account 
for these limitations?   
 
N. TIMELINE OF VISITS, MEASURES AND FORMS: 
 
Table 1 Timeline of Visits and Data Collection 
 
Screening 
& 
Enrollment 
Inpatient 
(post-op) 
Follow-
up 
(Clinic- 2 
weeks) 
1 
Month 
3 
Months 
6 
Months 
Specific 
Aim  
(1 or 2) 
Eligibility 
X 
X* 
 
 
 
 
1/2 

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Consent 
X 
 
 
 
 
 
1/2 
Demographics 
X 
 
 
 
 
 
1/2 
Charlson 
Comorbidity 
Index 
X 
 
 
 
 
 
1/2 
Quality of Life 
Assessment 
X 
 
X 
X 
X 
X 
 
1 
Randomization  
X 
 
 
 
 
 
Adverse Events  
 
X 
X 
X 
X 
2 
Hospital LOS 
 
 
X 
 
 
 
1/2 
Costs 
 
 
 
 
 
X 
1/2 
*assess for continued study eligibility prior to randomization 
O. RESEARCH COSTS 
Costs incurred by the study will be borne by unrestricted Section of Thoracic 
Surgery research funds.  Only those patients with insurance that does not cover 
the post-operative tube feeding will be paid for by the Section of Thoracic 
Surgery.  There are no costs for data collection that will be charged to the 
patient.  
 
P. REFERENCES CITED 
Early enteral feeding compared with parenteral nutrition after oesophageal 
or oesophagogastric resection and reconstruction. 
Gabor S, Renner H, Matzi V, Ratzenhofer B, Lindenmann J, Sankin O, Pinter H, 
Maier A, Smolle J, Smolle-Jüttner FM. 
Br J Nutr. 2005 Apr;93(4):509-13. 
PMID: 15946413  
 
Fit for surgery: an expert panel review on optmising patients prior to surgery, 
with a particular focus on nutrition. 
Windsor A, Braga M, Martindale R, Buenos R, Tepaske R, Kraehenbuehl L, 
Weimann A. 
Surgeon. 2004 Dec;2(6):315-9. Review. 
PMID: 15712570 
 
Immunonutrition in patients undergoing esophageal cancer resection. 
Mudge L, Isenring E, Jamieson GG. 
Dis Esophagus. 2011 Apr;24(3):160-5. doi: 10.1111/j.1442-
2050.2010.01117.x. Epub 2010 Oct 13. Review. 
PMID: 20946133 
 

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An evidence-based approach to perioperative nutrition support in the elective 
surgery patient. 
Miller KR, Wischmeyer PE, Taylor B, McClave SA. 
JPEN J Parenter Enteral Nutr. 2013 Sep;37(5 Suppl):39S-50S. doi: 
10.1177/0148607113493928. 
PMID: 24009248 
 
Enteral nutrition enriched with eicosapentaenoic acid (EPA) preserves lean 
body mass following esophageal cancer surgery: results of a double-blinded 
randomized controlled trial. 
Ryan AM, Reynolds JV, Healy L, Byrne M, Moore J, Brannelly N, McHugh A, 
McCormack D, Flood P. 
Ann Surg. 2009 Mar;249(3):355-63. doi: 10.1097/SLA.0b013e31819a4789. 
PMID: 19247018 

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Figure 1 Study Design 
Patient meets all inclusion and no 
exclusion critieria to enroll into the 
study
Consent/Enrollement in Study
Randomization
Group A:
Continue Tube Feeding (for at least 
50% of caloric need) for 1 month 
post-operatively
Follow-up:
2-3 weeks- Clinic
1-month- mail
3 months- mail
6 months- mail
Group B:
Discontinue tube feeding