Impact of early enteral versus parenteral nutrition on mortality in patients requiring mechanical ventilation and catecholamines: study protocol for a randomized controlled trial (NUTRIREA-2)

Laurent Brisard, Amélie Le Gouge, Jean-Baptiste Lascarrou, Hervé Dupont, Pierre Asfar, Michel Sirodot, Gael Piton, Hoang-Nam Bui, Olivier Gontier, Ali Ait Hssain, Stéphane Gaudry, Jean-Philippe Rigaud, Jean-Pierre Quenot, Virginie Maxime, Carole Schwebel, Didier Thévenin, Saad Nseir, Erika Parmentier, Ahmed El Kalioubie, Mercé Jourdain, Véronique Leray, Nathalie Rolin, Frédéric Bellec, Vincent Das, Frédérique Ganster, Christophe Guitton, Karim Asehnoune, Anne Bretagnol, Nadia Anguel, Jean-Paul Mira, Emmanuel Canet, Bertrand Guidet, Michel Djibre, Benoit Misset, René Robert, Frédéric Martino, Philippe Letocart, Daniel Silva, Michael Darmon, Vlad Botoc, Jean Etienne Herbrecht, Ferhat Meziani, Jérôme Devaquet, Emmanuelle Mercier, Jack Richecoeur, Stéphanie Martin, Emilie Gréau, Bruno Giraudeau, Jean Reignier, Laurent Brisard, Amélie Le Gouge, Jean-Baptiste Lascarrou, Hervé Dupont, Pierre Asfar, Michel Sirodot, Gael Piton, Hoang-Nam Bui, Olivier Gontier, Ali Ait Hssain, Stéphane Gaudry, Jean-Philippe Rigaud, Jean-Pierre Quenot, Virginie Maxime, Carole Schwebel, Didier Thévenin, Saad Nseir, Erika Parmentier, Ahmed El Kalioubie, Mercé Jourdain, Véronique Leray, Nathalie Rolin, Frédéric Bellec, Vincent Das, Frédérique Ganster, Christophe Guitton, Karim Asehnoune, Anne Bretagnol, Nadia Anguel, Jean-Paul Mira, Emmanuel Canet, Bertrand Guidet, Michel Djibre, Benoit Misset, René Robert, Frédéric Martino, Philippe Letocart, Daniel Silva, Michael Darmon, Vlad Botoc, Jean Etienne Herbrecht, Ferhat Meziani, Jérôme Devaquet, Emmanuelle Mercier, Jack Richecoeur, Stéphanie Martin, Emilie Gréau, Bruno Giraudeau, Jean Reignier

Abstract

Background: Nutritional support is crucial to the management of patients receiving invasive mechanical ventilation (IMV) and the most commonly prescribed treatment in intensive care units (ICUs). International guidelines consistently indicate that enteral nutrition (EN) should be preferred over parenteral nutrition (PN) whenever possible and started as early as possible. However, no adequately designed study has evaluated whether a specific nutritional modality is associated with decreased mortality. The primary goal of this trial is to assess the hypothesis that early first-line EN, as compared to early first-line PN, decreases day 28 all-cause mortality in patients receiving IMV and vasoactive drugs for shock.

Methods/design: The NUTRIREA-2 study is a multicenter, open-label, parallel-group, randomized controlled trial comparing early PN versus early EN in critically ill patients requiring IMV for an expected duration of at least 48 hours, combined with vasoactive drugs, for shock. Patients will be allocated at random to first-line PN for at least 72 hours or to first-line EN. In both groups, nutritional support will be started within 24 hours after IMV initiation. Calorie targets will be 20 to 25 kcal/kg/day during the first week, then 25 to 30 kcal/kg/day thereafter. Patients receiving PN may be switched to EN after at least 72 hours in the event of shock resolution (no vasoactive drugs for 24 consecutive hours and arterial lactic acid level below 2 mmol/L). On day 7, all patients receiving PN and having no contraindications to EN will be switched to EN. In both groups, supplemental PN may be added to EN after day 7 in patients with persistent intolerance to EN and inadequate calorie intake. We plan to recruit 2,854 patients at 44 participating ICUs.

Discussion: The NUTRIREA-2 study is the first large randomized controlled trial designed to assess the hypothesis that early EN improves survival compared to early PN in ICU patients. Enrollment started on 22 March 2013 and is expected to end in November 2015.

Trial registration: ClinicalTrials.gov Identifier: NCT01802099 (registered 27 February 2013).

Figures

Figure 1
Figure 1
Study protocol. D, Day; EN, Enteral nutrition; ICU, Intensive care unit; PN, Parenteral nutrition.
Figure 2
Figure 2
Protocol for managing upper gastrointestinal intolerance. GI, Gastrointestinal; NGT, Nasogastric tube. Response J Reignier: this is correct.
Figure 3
Figure 3
Protocol for diarrhea management.
Figure 4
Figure 4
Flow diagram of NUTRIREA-2 trial according to CONSORT.

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