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Nutritional support is a key component of therapy in such cases, which is related to the high prevalence of malnutrition. In the prophylactic setting, enteral nutrition (EN) is associated with a shorter hospital stay, a lower incidence of severe infectious complications, lower severity of complications and decreased cost compared to total parenteral nutrition (TPN) following major upper gastrointestinal (GI) surgery. There is little evidence available for the curative setting after fistula occurrence. We hypothesize that EN increases the 30-day fistula closure rate in PUGIF, allowing better health-related quality of life without increasing the morbidity or mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods\/design<\/jats:title>\n                    <jats:p>The NUTRILEAK trial is a multicenter, randomized, parallel-group, open-label phase III trial to assess the efficacy of EN (the experimental group) compared with TPN (the control group) in patients with PUGIF. The primary objective of the study is to compare EN versus TPN in the treatment of PUGIF (after esophagogastric resection including bariatric surgery, duodenojejunal resection or pancreatic resection with digestive tract violation) in terms of the 30-day fistula closure rate. Secondary objectives are to evaluate the 6-month postrandomization fistula closure rate, time of first fistula closure (in days), the medical- and surgical treatment-related complication rate at 6\u2009months after randomization, the fistula-related complication rate at 6\u2009months after randomization, the type and severity of early (30\u2009days after randomization) and late fistula-related complications (over 30\u2009days after randomization), 30-day and 6-month postrandomization mortality rate, nutritional status at day 30, day 60, day 90 and day 180 postrandomization, the mean length of hospital stay, the patient\u2019s health-related quality of life (by self-assessment questionnaire), oral feeding time and direct costs of treatment. A total of 321 patients will be enrolled.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The two nutritional supports are already used in daily practice, but most surgeons are reluctant to use the enteral route in case of PUGIF. This study will be the first randomized trial testing the role of EN versus TPN in PUGIF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03742752\">NCT03742752<\/jats:ext-link>\n                      . Registered on 14 November 2018.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-020-04366-3","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T04:04:32Z","timestamp":1591070672000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Enteral versus parenteral nutrition in the conservative treatment of upper gastrointestinal fistula after surgery: a multicenter, randomized, parallel-group, open-label, phase III study (NUTRILEAK 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ID-RCB 2018-A01625\u201350) and we will not begin recruiting at other centers in the trial until local ethical approval has been obtained. The study complies with the Declaration of Helsinki and the principles of good clinical practice guidelines. Informed consent is obtained from each patient in written form prior to randomization. Patients will be informed about the objectives, the nature, the duration and the possible adverse consequences of the trial by a surgeon familiar with the study, orally and with the help of an information letter approved by the ethics committee. Patient safety and all potential threats to the patients are monitored at each consultation. A Data and Safety Monitoring Board is not necessary because the aim of the study is to compare treatments already used in practice. Sponsor representatives will regularly review data collected on the electronic case report form at each participating site and on the basis of patient files present at those sites under the conditions defined by a monitoring plan. Any information deemed to potentially affect the safety of the trial will be brought to the attention of the sponsor.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"448"}}