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 study)
Background: Postoperative Upper Gastro-Intestinal Fistula (PUGIF) is a devastating complication, leading to a high mortality rate reaching up to 80%, increased length of hospital stay, reduced Health related quality of life (HRQOL) and increased health costs. Nutritional support is a key component of therapy in such cases, related to the high prevalence of malnutrition. In prophylactic setting, enteral nutrition (EN) is associated to shorter hospital stay, 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. In curative settingafter fistula occurrence, there are very few evidences available. We hypothesise that EN increases 30-day fistula closure rate in PUGIF, allowing better HRQOL without increasing morbi-mortality. Methods/Design: The NUTRILEAK trial is a multicenter, randomized, parallel-group, open label phase III trial to assess the efficacy of EN (experimental group) compared with TPN (control group) in patients with PUGIF. The primary objective of the study is to compare EN versus TPN in the treatment of PUGIF (after oesophago-gastric resection including bariatric surgery, duodeno-jejunal resection or pancreatic resection with digestive tract violation) in terms of 30-day fistula closure rate. Secondary objectives are to evaluate the 6-month post-randomization fistula closure rate, time of first fistula closure (in days), medical and surgical treatment-related complication rate at 6 months after randomization, fistula related complication rate at 6 months after randomization, type and severity of early (30 days after randomization) and late fistula-related complications (over 30 days after randomization), 30-day and 6-month post-randomization mortality rate, nutritional status at day 30, day 60, day 90 and day 180 post randomization, mean length of hospital stay, patient’s Health related quality of life (HRQOL) (self-assessment questionnaire), oral feeding time anddirect costs of treatment. A total of 321 patients will be enrolled. Discussion: 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. Trial registration: ClinicalTrials.gov, NCT03742752. Registered on 14 November 2018.