Impact of Early Low-Calorie Low-Protein Versus Standard Feeding on Outcomes of Ventilated Adults With Shock

NCT ID: NCT03573739

Last Updated: 2022-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 3044 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-05
• Study Completion Date: 2021-12-24

Brief Summary

Among critically ill patients requiring mechanical ventilation and catecholamines for shock, nearly 40% to 50% die, and functional recovery is often delayed in survivors. International guidelines include early nutritional support (≤48 h after admission), 20-25 kcal/kg/d at the acute phase, and 1.2-2 g/kg/d protein. These targets are rarely achieved in patients with severe critically illnesses. Recent data challenge the wisdom of providing standard amounts of calories and protein during the acute phase of critical illness. Studies designed to improve enteral nutrition delivery showed no outcome benefits with higher intakes. Instead, adding parenteral nutrition to increase intakes was associated with longer ICU stays and more infectious complications. Studies suggest that higher protein intakes during the acute phase may be associated with greater muscle wasting and ICU-acquired weakness. 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 potentially associated with improved muscle preservation, translating into shorter mechanical ventilation and ICU-stay durations, lower ICU-acquired infection rates, lower mortality, and better long-term clinical outcomes. This multicentre, randomized, controlled, open trial will compare, in patients receiving mechanical ventilation and treated with vasoactive agent for shock two strategies for initiating nutritional support at the acute phase of ICU management (D0-D7): early calorie/protein restriction (6 kcal/kg/d/0.2-0.4 g/kg/d, Low group) or standard calorie/protein targets (25 kcal/kg/d/1.0-1.3 g/kg/d, Standard group). Patients in both groups will receive enteral or parenteral nutrition appropriate for their critical illness. Two alternative primary end-points will be evaluated: all-cause mortality by day 90 and time to discharge alive from the ICU. Second end-points will be calories and proteins delivered, nosocomial infections, gastro-intestinal complications, glucose control, liver dysfunctions, muscle function at the time of readiness for ICU discharge and quality of life at 3 months and 1 year after study inclusion.

Conditions

Critical Illness; Shock; Mechanical Ventilation; Critical Illness Myopathy; Nosocomial Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Low group

Patients randomized in the "low group" will receive a low-calorie low-protein nutrition regimen during the acute phase.

Group Type: EXPERIMENTAL

low-calorie low-protein

Intervention Type: PROCEDURE

In the low-calorie low-protein (Low) group, the calorie target will be 6 kcal/kg/day and the protein target 0.2-0.4 g/kg/d during the acute phase, i.e. from D0 to D7. On D8, the calorie target will be 30 kcal/kg/d and the protein target 1.2-2.0 g/kg/d.

Standard group

Patients randomized in the "standard group" will receive a standard-calorie/standard-protein nutrition regimen during the acute phase.

Group Type: ACTIVE_COMPARATOR

standard-calorie/standard-protein

Intervention Type: PROCEDURE

In the standard-calorie/standard-protein (Standard) group, the first-line calorie target calculated based on body weight is 25 kcal/kg/day and the protein target 1.0-1.3 g/kg/d during the acute phase, i.e. from D0 to D7. On D8, the calorie target will be 30 kcal/kg/d and the protein target 1.2-2.0 g/kg/d.

Interventions

low-calorie low-protein

In the low-calorie low-protein (Low) group, the calorie target will be 6 kcal/kg/day and the protein target 0.2-0.4 g/kg/d during the acute phase, i.e. from D0 to D7. On D8, the calorie target will be 30 kcal/kg/d and the protein target 1.2-2.0 g/kg/d.

Intervention Type: PROCEDURE

standard-calorie/standard-protein

In the standard-calorie/standard-protein (Standard) group, the first-line calorie target calculated based on body weight is 25 kcal/kg/day and the protein target 1.0-1.3 g/kg/d during the acute phase, i.e. from D0 to D7. On D8, the calorie target will be 30 kcal/kg/d and the protein target 1.2-2.0 g/kg/d.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Invasive mechanical ventilation started in the ICU within the past 24 h, or started before ICU admission with ICU admission within the past 24 h, for an expected duration of at least 48 hours after inclusion
• Treatment with a vasoactive agent for shock (adrenaline, dobutamine, or noradrenaline)
• Nutritional support expected to be started within 24 h after intubation or within 24 h after ICU admission when mechanical ventilation was started before ICU admission
• Age older than 18 years
• Patient and/or next-of-kin informed about the study and having consented to participation in the study. If the patient is unable to receive information and no next-of-kin can be contacted during screening for the study, trial inclusion will be completed as an emergency procedure by the ICU physician, in compliance with the French law.

Exclusion Criteria

• Specific nutritional needs, such as pre-existing long-term home enteral or parenteral nutrition, for chronic bowel disease
• Dying patient, not-to-be-resuscitated order, or other treatment limitation decision at ICU admission
• Pregnancy, recent delivery, or lactation
• Adult under guardianship
• Department of corrections inmate

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

University Hospital, Tours

OTHER

Sponsor Role: collaborator

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean Reignier, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Locations

Chu de La Reunion Site Nord

Saint-Denis, La Réunion, France

Chu Amiens Picardie

Amiens, , France

CHU Angers

Angers, , France

Centre Hospitalier D'Angouleme

Angoulême, , France

Ch Annecy-Genevois

Annecy, , France

Centre Hospitalier D'Argenteuil

Argenteuil, , France

Hôpital du bois brulé

Beauvais, , France

Hôpital Nord Franche Comté

Belfort, , France

Chu Jean Minjoz

Besançon, , France

Hôpital de Béthune

Béthune, , France

Hôpital Avicenne AP-HP

Bobigny, , France

Hopital Pellegrin Chu

Bordeaux, , France

CHU Cavale Blanche

Brest, , France

Ch Chartres Louis Pasteur

Chartres, , France

Chu Gabriel Montpied

Clermont-Ferrand, , France

Hopital Louis Mourier (Ap-Hp)

Colombes, , France

Ch Dieppe

Dieppe, , France

Chu Bocage

Dijon, , France

Hôpital Raymond-Poincaré

Garches, , France

Hôpital Michalon

Grenoble, , France

Chd Les Oudairies

La Roche-sur-Yon, , France

Chu Bicetre

Le Kremlin-Bicêtre, , France

Centre Hospitalier Du Mans

Le Mans, , France

CH Emile Roux

Le Puy-en-Velay, , France

Centre Hospitalier de Lens

Lens, , France

Chr - Hopital Roger Salengro

Lille, , France

CH Saint-Philibert

Lomme, , France

Hopital de La Croix-Rousse

Lyon, , France

Hopital Edouard Herriot

Lyon, , France

Centre Hospitalier Marc Jacquet

Melun, , France

Centre Hospitalier de Montauban

Montauban, , France

Hopital Saint Eloi

Montpellier, , France

Ctre Hosp Intercomm Andre Gregoire

Montreuil, , France

Chu de Nantes

Nantes, , France

CHU Nantes

Nantes, , France

Chr D'Orleans

Orléans, , France

Hopital Lariboisiere

Paris, , France

Hôpital Saint Louis (AP-HP)

Paris, , France

Hopital Saint Antoine

Paris, , France

Hopital Pitie Salpetriere

Paris, , France

CHU Paris Cochin

Paris, , France

G.I.H. Bichat / Claude Bernard (Ap-Hp)

Paris, , France

Hopital Europeen Georges Pompidou

Paris, , France

CH Pau

Pau, , France

Chu La Miletrie

Poitiers, , France

C.H.R. Pontchaillou

Rennes, , France

C.H. de Rodez Hopital Jacques Puel

Rodez, , France

Hopital Charles Nicolle Chu Rouen

Rouen, , France

CH Saint Brieuc

Saint-Brieuc, , France

Ch General Delafontaine

Saint-Denis, , France

CHU de Saint Etienne

Saint-Priest-en-Jarez, , France

Hopital Broussais

St-Malo, , France

Hôpital de Hautepierre CHU de Strasbourg

Strasbourg, , France

Hopital Foch

Suresnes, , France

CH de Bigorre

Tarbes, , France

CHU DE TOURS Bretonneau

Tours, , France

CH Valenciennes

Valenciennes, , France

Centre Hospitalier Bretagne Atlantique - Vannes Auray

Vannes, , France

CHU Pointe à Pitre - Abymes

Pointe-à-Pitre, , Guadeloupe

Countries

France; Guadeloupe

References

Reignier J, Plantefeve G, Mira JP, Argaud L, Asfar P, Aissaoui N, Badie J, Botoc NV, Brisard L, Bui HN, Chatellier D, Chauvelot L, Combes A, Cracco C, Darmon M, Das V, Debarre M, Delbove A, Devaquet J, Dumont LM, Gontier O, Groyer S, Guerin L, Guidet B, Hourmant Y, Jaber S, Lambiotte F, Leroy C, Letocart P, Madeux B, Maizel J, Martinet O, Martino F, Maxime V, Mercier E, Nay MA, Nseir S, Oziel J, Picard W, Piton G, Quenot JP, Reizine F, Renault A, Richecoeur J, Rigaud JP, Schneider F, Silva D, Sirodot M, Souweine B, Tamion F, Terzi N, Thevenin D, Thiery G, Thieulot-Rolin N, Timsit JF, Tinturier F, Tirot P, Vanderlinden T, Vinatier I, Vinsonneau C, Voicu S, Lascarrou JB, Le Gouge A; NUTRIREA-3 Trial Investigators; Clinical Research in Intensive Care; Sepsis (CRICS-TRIGGERSEP)Group. Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3). Lancet Respir Med. 2023 Jul;11(7):602-612. doi: 10.1016/S2213-2600(23)00092-9. Epub 2023 Mar 20.

Reference Type: DERIVED

PMID: 36958363 (View on PubMed)

Reignier J, Le Gouge A, Lascarrou JB, Annane D, Argaud L, Hourmant Y, Asfar P, Badie J, Nay MA, Botoc NV, Brisard L, Bui HN, Chatellier D, Chauvelot L, Combes A, Cracco C, Darmon M, Das V, Debarre M, Delbove A, Devaquet J, Voicu S, Aissaoui-Balanant N, Dumont LM, Oziel J, Gontier O, Groyer S, Guidet B, Jaber S, Lambiotte F, Leroy C, Letocart P, Madeux B, Maizel J, Martinet O, Martino F, Mercier E, Mira JP, Nseir S, Picard W, Piton G, Plantefeve G, Quenot JP, Renault A, Guerin L, Richecoeur J, Rigaud JP, Schneider F, Silva D, Sirodot M, Souweine B, Reizine F, Tamion F, Terzi N, Thevenin D, Thiery G, Thieulot-Rolin N, Timsit JF, Tinturier F, Tirot P, Vanderlinden T, Vinatier I, Vinsonneau C, Maugars D, Giraudeau B. 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). BMJ Open. 2021 May 11;11(5):e045041. doi: 10.1136/bmjopen-2020-045041.

Reference Type: DERIVED

PMID: 33980526 (View on PubMed)

Other Identifiers

RC18_0006

Identifier Type: -

Identifier Source: org_study_id