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)

Caroline Gronnier, Cécile Chambrier, Alain Duhamel, Benoît Dervaux, Denis Collet, Delphine Vaudoyer, Jean-Marc Régimbeau, Jacques Jougon, Jérémie Théréaux, Gil Lebreton, Julie Veziant, Alain Valverde, Pablo Ortega-Deballon, François Pattou, Muriel Mathonnet, Julie Perinel, Laura Beyer-Berjot, David Fuks, Philippe Rouanet, Jérémie H Lefevre, Pierre Cattan, Sophie Deguelte, Bernard Meunier, Jean-Jacques Tuech, Patrick Pessaux, Nicolas Carrere, Ephrem Salame, Eleonor Benaim, Bertrand Dousset, Simon Msika, Christophe Mariette, Guillaume Piessen, FRENCH association, Caroline Gronnier, Cécile Chambrier, Alain Duhamel, Benoît Dervaux, Denis Collet, Delphine Vaudoyer, Jean-Marc Régimbeau, Jacques Jougon, Jérémie Théréaux, Gil Lebreton, Julie Veziant, Alain Valverde, Pablo Ortega-Deballon, François Pattou, Muriel Mathonnet, Julie Perinel, Laura Beyer-Berjot, David Fuks, Philippe Rouanet, Jérémie H Lefevre, Pierre Cattan, Sophie Deguelte, Bernard Meunier, Jean-Jacques Tuech, Patrick Pessaux, Nicolas Carrere, Ephrem Salame, Eleonor Benaim, Bertrand Dousset, Simon Msika, Christophe Mariette, Guillaume Piessen, FRENCH association

Abstract

Background: Postoperative upper gastrointestinal fistula (PUGIF) is a devastating complication, leading to high mortality (reaching up to 80%), increased length of hospital stay, reduced health-related quality of life and increased health costs. 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.

Methods/design: 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 months after randomization, the fistula-related complication rate at 6 months after randomization, the type and severity of early (30 days after randomization) and late fistula-related complications (over 30 days 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's 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.

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.

Keywords: Conservative treatment; Enteral nutrition; Parenteral nutrition; Randomized controlled trial; Upper gastrointestinal fistula.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Schedule of the trial interventions and assessments. *Enteral nutrition (EN) or total parenteral nutrition (TPN) will be continued until the oral intake reaches at least 60% of daily requirements. **Computed tomography (CT) scan with contrast injection for patient who do not show any output of fluid during 48 h in wound or drainage. EQ5D EuroQol five dimensions, SF-36 36-item Short Form
Fig. 2
Fig. 2
Flowchart of the trial. D day, EN enteral nutrition, GI gastrointestinal, TPN total parenteral nutrition, V visit

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