BMJ Open (Jun 2021)
Impact of early low-calorie low-protein versus standard-calorie standard-protein feeding on outcomes of ventilated adults with shock: design and conduct of a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3)
- Fabienne Tamion,
- Nicolas Terzi,
- Jérôme Devaquet,
- Alain Combes,
- Gael Piton,
- Agathe Delbove,
- Christophe Leroy,
- Djillali Annane,
- Samuel Groyer,
- Florian Reizine,
- Pierre Asfar,
- Jack Richecoeur,
- Walter Picard,
- Michael Darmon,
- Emmanuelle Mercier,
- Amélie Le Gouge,
- Jean-Baptiste Lascarrou,
- Yannick Hourmant,
- Julio Badie,
- Nicolae-Vlad Botoc,
- Laurent Brisard,
- Hoang-Nam Bui,
- Delphine Chatellier,
- Louis Chauvelot,
- Christophe Cracco,
- Vincent Das,
- Matthieu Debarre,
- Sebastian Voicu,
- Nadia Aissaoui-Balanant,
- Louis-Marie Dumont,
- Johanna Oziel,
- Olivier Gontier,
- Fabien Lambiotte,
- Philippe Letocart,
- Benjamin Madeux,
- Olivier Martinet,
- Frédéric Martino,
- Anne Renault,
- Jean Philippe Rigaud,
- Francis Schneider,
- Daniel Silva,
- Michel Sirodot,
- Guillaume Thiéry,
- Nathalie Thieulot-Rolin,
- François Tinturier,
- Patrice Tirot,
- Thierry Vanderlinden,
- Isabelle Vinatier,
- Diane Maugars
Affiliations
- Fabienne Tamion
- Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Rouen, Rouen, France
- Nicolas Terzi
- Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire Grenoble Alpes Hopital Michallon, La Tronche, France
- Jérôme Devaquet
- Medical-Surgical Intensive Care Unit, Hôpital Foch, Suresnes, France
- Alain Combes
- Service de Médecine Intensive Réanimation, Hôpital Universitaire Pitié Salpêtrière, Paris, France
- Gael Piton
- Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Besancon, Besancon, France
- Agathe Delbove
- Réanimation Polyvalente, Centre Hospitalier Bretagne Atlantique, Vannes, France
- Christophe Leroy
- Service de Médecine Intensive Réanimation, Centre Hospitalier Emile Roux, Le Puy en Velay, France
- Djillali Annane
- Service de Médecine Intensive Réanimation, Hôpital Raymond Poincaré, Garches, France
- Samuel Groyer
- Service de Médecine Intensive Réanimation, Centre Hospitalier de Montauban, Montauban, France
- Florian Reizine
- Service de Médecine Intensive et Réanimation, Centre Hospitalier Universitaire de Rennes, Rennes, France
- Pierre Asfar
- Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire d`Angers, Angers, France
- Jack Richecoeur
- Service de Médecine Intensive Réanimation, Centre Hospitalier de Beauvais, Beauvais, France
- Walter Picard
- Service de Médecine Intensive Réanimation, Centre Hospitalier de Pau, Pau, France
- Michael Darmon
- Service de Médecine Intensive Réanimation, Hôpital Saint-Louis, Paris, France
- Emmanuelle Mercier
- Service de Médecine Intensive Réanimation, Centre Hospitalier Régional Universitaire de Tours, Tours, France
- Amélie Le Gouge
- INSERM CIC 1415, Centre Hospitalier Regional Universitaire de Tours, Tours, France
- Jean-Baptiste Lascarrou
- Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Nantes, Nantes, France
- Yannick Hourmant
- Pôle Anesthésie Réanimations, Service d`Anesthésie Réanimation Chirurgicale, CHU Nantes, Nantes, France
- Julio Badie
- Service de Médecine Intensive Réanimation, Hôpital Nord Franche-Comté, Montbeliard, France
- Nicolae-Vlad Botoc
- Service de Médecine Intensive Réanimation, Centre Hospitalier de Saint-Malo, Saint-Malo, France
- Laurent Brisard
- Service d`Anesthésie Réanimation Chirurgicale, CHU Nantes, Nantes, France
- Hoang-Nam Bui
- Service de Médecine Intensive Réanimation, CHU de Bordeaux, Bordeaux, France
- Delphine Chatellier
- Service de Médecine Intensive Réanimation, CHU Poitiers, Poitiers, France
- Louis Chauvelot
- Service de Médecine Intensive Réanimation, CHU Lyon, Lyon, France
- Christophe Cracco
- Service de Médecine Intensive Réanimation, Centre Hospitalier d`Angouleme, Angouleme, France
- Vincent Das
- Médecine Intensive Réanimation, CHI André Grégoire, Montreuil, France
- Matthieu Debarre
- Médecine Intensive Réanimation, Centre Hospitalier de Saint Brieuc, Saint Brieuc, France
- Sebastian Voicu
- Médecine Intensive Réanimation, Hopital Lariboisiere, Paris, France
- Nadia Aissaoui-Balanant
- Médecine Intensive Réanimation, Hôpital Europeen Georges-Pompidou - Broussais, Paris, France
- Louis-Marie Dumont
- Service de Médecine Intensive Réanimation, Hôpital Louis-Mourier, Colombes, France
- Johanna Oziel
- Service de Médecine Intensive Réanimation, Hôpital Avicenne, Bobigny, France
- Olivier Gontier
- Service de Médecine Intensive Réanimation, Centre Hospitalier de Chartres, Chartres, France
- Fabien Lambiotte
- Service de Médecine Intensive Réanimation, Centre Hospitalier de Valenciennes, Valenciennes, France
- Philippe Letocart
- Service de Médecine Intensive Réanimation, Centre Hospitalier de Rodez, Rodez, France
- Benjamin Madeux
- Service de Médecine Intensive Réanimation, Centre Hospitalier de Bigorre, Tarbes, France
- Olivier Martinet
- Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire de La Réunion, Saint-Denis, France
- Frédéric Martino
- Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire Pointe-à-Pitre Abymes, Pointe-a-Pitre, Guadeloupe
- Anne Renault
- Service de Médecine Intensive Réanimation, CHRU de Brest, Brest, France
- Jean Philippe Rigaud
- Service de Médecine Intensive Réanimation, Centre Hospitalier de Dieppe, Dieppe, France
- Francis Schneider
- Service de Médecine Intensive Réanimation, Hopitaux Universitaires de Strasbourg, Strasbourg, France
- Daniel Silva
- Service de Médecine Intensive Réanimation, Centre Hospitalier de Saint Denis, Saint Denis, France
- Michel Sirodot
- Service de Médecine Intensive Réanimation, Centre Hospitalier Annecy Genevois, Epagny Metz-Tessy, France
- Guillaume Thiéry
- Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Etienne, France
- Nathalie Thieulot-Rolin
- Service de Médecine Intensive Réanimation, Centre Hospitalier de Melun, Melun, France
- François Tinturier
- Réanimation Chirurgicale, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, France
- Patrice Tirot
- Service de Médecine Intensive Réanimation, Centre Hospitalier du Mans, Le Mans, France
- Thierry Vanderlinden
- Service de Médecine Intensive Réanimation, Institut Catholique de Lille, Lille, France
- Isabelle Vinatier
- Service de Médecine Intensive Réanimation, Centre Hospitalier Départemental Vendée, La Roche-sur-Yon, France
- Diane Maugars
- Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire de Nantes, Nantes, France
- DOI
- https://doi.org/10.1136/bmjopen-2020-045041
- Journal volume & issue
-
Vol. 11,
no. 5
Abstract
Introduction International guidelines include early nutritional support (≤48 hour after admission), 20–25 kcal/kg/day, and 1.2–2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets.Methods and analysis NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2–0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0–1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes.Ethics and dissemination The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals.Trial registration number NCT03573739.