Enteral Versus Parenteral Nutrition in the Conservative Treatment of Upper Gastrointestinal Fistula After Surgery

Study Overview
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Brief Summary
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The incidence of clinically significant anastomotic leaks (AL) after upper gastrointestinal (GI) surgery is approximately 4 % - 20 %, and the associated mortality can be as high as 80 % . Nutritional support is a key component of therapy in such cases, related to high prevalence of malnutrition and nil per month required for leak treatment. In the prophylactic setting, before the occurrence of any AL, a literature review based on seven randomised trials showed that enteral nutrition (EN) is associated with shorter hospital stay, lower incidence of severe of infectious complications, lower severity of complications and decreased cost compared to parenteral nutrition (TPN) following major upper GI surgery . In the curative setting, after the AL occurrence, very few evidence is available. Only one randomized clinical trial suggested the superiority of EN versus TPN after pancreatic surgery with a increase of the 30-day fistula closure rate from 37% in the TPN group to 60% in the EN group . This sole randomised study available did not include all postoperative upper GI AL (PUGIAL) that can occur after esophageal, gastric, duodenal, pancreatic surgery (including obesity surgery), whereas the concept of enteral nutritional support is highly relevant for all these situations. However surgeons are usually reluctant to provide EN in case of AL. A randomized study suggested the feasibility of EN in 47 patients with upper GI AL but no randomized study to date has been designed to test the superiority of EN versus TPN in PUGIAL. The study aim is to demonstrate the superiority of EN versus TPN to accelerate AL healing after upper GI surgery. Hypothesis: EN increases the 30-day fistula closure rate in PUGIAL, allowing better HRQOL without increasing morbi-mortality.

Official Title
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Enteral Versus Parenteral Nutrition in the Conservative Treatment of Upper Gastrointestinal Fistula After Surgery: a Multicenter, Randomized, Parallel-group, Open Label

Conditions
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Gastrointestinal Fistula, Enteral Nutritional Support

Intervention / Treatment
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* Other: Enteral nutrition
* Other: Parenteral nutrition


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years Patients having received upper GI surgery for benign or malignant disease including, oesophageal, gastric, duodenal or pancreatic surgery or bariatric surgery Diagnosis of an active postoperative fistula or persisting after a failure of surgical or endoscopic procedure dedicated to close the fistula AL diagnosed from less than 72h AND confirmed on at least two criteria among the followings: clinical symptoms of AL ct scan / ultrason imaging and /or endoscopic diagnosis of AL biologic/bacteriology diagnosis on fluid output intraoperative diagnosis of AL at time of reoperation Indication of nil per mouth American society of anesthesiologist score 1, 2 or 3 In case of neoplasm, absence of peritoneal carcinomatosis or distant metastasis No severe concomitant uncontrolled disease Life expectancy more than 6 months No history of allergy or study product intolerance Ongoing healthcare insurance Exclusion Criteria: - Scheduled surgical or endoscopic treatment with the aim to close the fistula (suture, prosthesis, clip or glue). In case of such treatment failure, patients are eligible to participate to the study. Endoscopic or surgical drainage are not exclusion criteria (meaning that drainage only is authorized before randomization) History of or current severe uncontrolled cardiovascular, pulmonary, renal or liver failure Uncontrolled sepsis related to the AL Malnutrition requiring combined nutritional treatment with the enteral AND parenteral routes together Untreated or persistent Peritoneal carcinomatosis or distant metastasis Pregnant and/or lactating women Freedom privacy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enteral Nutrition (EN)<br>To demonstrate the superiority of EN versus TPN in the treatment of postoperative upper GI anastomotic leak (PUGIAL) after upper GI surgery (including esophageal, gastric, duodenal, pancreatic and obesity surgery). Patients will be randomized to receive EN through jejunostomy or nasojejunal tube until oral diet covering at least 60% of their daily requirement | Other: Enteral nutrition<br>* administration of enteral nutrition<br>|
| Active Comparator: Parenteral Nutrition (TPN)<br>Patients will be randomized to receive TPN through central venous access, piccline or totally implantable venous access port tube until oral diet covering at least 60% of their daily requirement | Other: Parenteral nutrition<br>* administration of parenteral nutrition<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30-day fistula closure rate | Fistula closure will be defined as an output of no fluid for at least 48 hours in wound or drainage AND absence of any fluid collection on imaging (Computed Tomography scan with injection of contrast product). | 30 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-month fistula closure rate | Percentage of patients having their fistula closed according to the definition above within 6 months after randomization | at 6 months after randomization | 
| Time to first fistula closure | Time to first fistula closure defined as time in days from randomization to first AL closure within 6 months after randomization | at 6 months after randomization | 
| Treatment-related complications | number of patients presenting at least one complication related to the nutritional support (catheter related infection or thrombosis, tube related complication) | longitudinal evaluation during all the study duration (from randomization to 6 months) | 
| Postoperative mortality rate | rate of death after operation | at 30 days after randomization | 
| Postoperative morbidity rate | rate of patients with a Clavien-Dindo grade 3-4-5 complications | at 30 days after randomization | 
| Weight | in kg | longitudinal evaluation during all the study duration (from randomization to 6 months) | 
| Albumin and prealbumin | in g/L | longitudinal evaluation during all the study duration (from randomization to 6 months) | 
| C reactive protein | mg/L | longitudinal evaluation during all the study duration (from randomization to 6 months) | 
| Grip test | muscular strength | longitudinal evaluation during all the study duration (from randomization to 6 months) | 
| Length of hospital stay in healthcare structure | Length of hospital stay in healthcare structure (including home hospitalization) based on the number of days of hospitalization | from the randomization until the end of hospitalization, up to 6 months | 
| Short form questionnaire 36 (SF-36) | Patient's Health-related quality of life (HRQOL) score. The SF-36 includes a single-item measure of health transition or change. he SF-36® Health Survey items and scales were constructed using the Likert method of summated ratings.4 Answers to each question are scored (some items need to be recoded). These scores are then summed to produce raw scale scores for each health concept which are then transformed to a 0 - 100 scale. Thie higher the score is, the better the quality of life is. | at inclusion, day 30, day 60, 3 months and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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enteral nutrition, parenteral nutrition, gastrointestinal fistula