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

NCT03573739 | Completed DMC

• 1 other identifier: RC18_0006
• Study Type: interventional
• Target: 3,044
• Locations: 2 countries
• Sites: 59

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

Outcome Measures

Primary Outcomes (2)

• Time to discharge alive from the ICU.

  A patient will be considered ready for ICU discharge by the bedside physicians as soon as all predefined clinical conditions for ICU discharge are fulfilled, regardless of ward-bed availability.

  From date of ICU admission until the date of first documented date when predefined clinical conditions for ICU discharge are fulfilled, an average of 10 days.

• D-90 mortality

  All-cause mortality by day 90

  90 days

Secondary Outcomes (31)

• Number of calories (in kcal) delivered daily enterally and/or parenterally

  from day 0 to day 7

• Ratio of prescribed over calories delivered

  from day 0 to day 7

• Proportion of patients who achieved their calorie target

  from day 0 to day 7

• Protein supply

  from day 0 to day 7

• Volume of fluids

  from day 0 to day 7

Study Arms (2)

Low group

EXPERIMENTAL

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

Procedure: low-calorie low-protein

Standard group

ACTIVE COMPARATOR

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

Procedure: standard-calorie/standard-protein

Interventions

low-calorie low-protein 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.

Low group

standard-calorie/standard-protein 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.

Standard group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nantes University Hospital: lead
• Ministry of Health, France: collaborator
• University Hospital, Tours: collaborator

Study Sites (59)

Chu de La Reunion Site Nord

Saint-Denis, La Réunion, 97405, France

Location

Chu Amiens Picardie

Amiens, 80054, France

Location

CHU Angers

Angers, 49100, France

Location

Centre Hospitalier D'Angouleme

Angoulême, 16959, France

Location

Ch Annecy-Genevois

Annecy, 74374, France

Location

Centre Hospitalier D'Argenteuil

Argenteuil, 95100, France

Location

Hôpital du bois brulé

Beauvais, 60000, France

Location

Hôpital Nord Franche Comté

Belfort, 90015, France

Location

Chu Jean Minjoz

Besançon, 25030, France

Location

Hôpital de Béthune

Béthune, 62408, France

Location

Hôpital Avicenne AP-HP

Bobigny, 93000, France

Location

Hopital Pellegrin Chu

Bordeaux, 33000, France

Location

CHU Cavale Blanche

Brest, 29609, France

Location

Ch Chartres Louis Pasteur

Chartres, 28630, France

Location

Chu Gabriel Montpied

Clermont-Ferrand, 63003, France

Location

Hopital Louis Mourier (Ap-Hp)

Colombes, 92701, France

Location

Ch Dieppe

Dieppe, 76202, France

Location

Chu Bocage

Dijon, 21079, France

Location

Hôpital Raymond-Poincaré

Garches, 92380, France

Location

Hôpital Michalon

Grenoble, 38043, France

Location

Chd Les Oudairies

La Roche-sur-Yon, 85025, France

Location

Chu Bicetre

Le Kremlin-Bicêtre, 94270, France

Location

Centre Hospitalier Du Mans

Le Mans, 72037, France

Location

CH Emile Roux

Le Puy-en-Velay, 43000, France

Location

Centre Hospitalier de Lens

Lens, 62300, France

Location

Chr - Hopital Roger Salengro

Lille, 59037, France

Location

CH Saint-Philibert

Lomme, 59462, France

Location

Hopital de La Croix-Rousse

Lyon, 69317, France

Location

Hopital Edouard Herriot

Lyon, 69437, France

Location

Centre Hospitalier Marc Jacquet

Melun, 77011, France

Location

Centre Hospitalier de Montauban

Montauban, 82013, France

Location

Hopital Saint Eloi

Montpellier, 34295, France

Location

Ctre Hosp Intercomm Andre Gregoire

Montreuil, 93100, France

Location

Chu de Nantes

Nantes, 44000, France

Location

CHU Nantes

Nantes, 44093, France

Location

Chr D'Orleans

Orléans, 86709, France

Location

Hopital Lariboisiere

Paris, 75010, France

Location

Hôpital Saint Louis (AP-HP)

Paris, 75010, France

Location

Hopital Saint Antoine

Paris, 75012, France

Location

Hopital Pitie Salpetriere

Paris, 75013, France

Location

CHU Paris Cochin

Paris, 75014, France

Location

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

Paris, 75877, France

Location

Hopital Europeen Georges Pompidou

Paris, 75908, France

Location

CH Pau

Pau, 64000, France

Location

Chu La Miletrie

Poitiers, 86021, France

Location

C.H.R. Pontchaillou

Rennes, 35033, France

Location

C.H. de Rodez Hopital Jacques Puel

Rodez, 12027, France

Location

Hopital Charles Nicolle Chu Rouen

Rouen, 76038, France

Location

CH Saint Brieuc

Saint-Brieuc, 22000, France

Location

Ch General Delafontaine

Saint-Denis, 93205, France

Location

CHU de Saint Etienne

Saint-Priest-en-Jarez, 42270, France

Location

Hopital Broussais

St-Malo, 35403, France

Location

Hôpital de Hautepierre CHU de Strasbourg

Strasbourg, 67098, France

Location

Hopital Foch

Suresnes, 92150, France

Location

CH de Bigorre

Tarbes, 65013, France

Location

CHU DE TOURS Bretonneau

Tours, 37044, France

Location

CH Valenciennes

Valenciennes, 59300, France

Location

Centre Hospitalier Bretagne Atlantique - Vannes Auray

Vannes, 56017, France

Location

CHU Pointe à Pitre - Abymes

Pointe-à-Pitre, 97159, Guadeloupe

Location

Related Publications (2)

• 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.

  PMID: 36958363 DERIVED

• 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.

  PMID: 33980526 DERIVED

MeSH Terms

Conditions

Critical Illness; Shock; Cross Infection

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Iatrogenic Disease

Study Officials

• Jean Reignier, MD, PhD

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This multicentre randomised controlled open trial compares two parallel groups of patients receiving mechanical ventilation and vasoactive amine therapy and given early nutritional support according to one of two strategies: 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/1.0-1.3g/kg/d: Standard group) at the acute phase of ICU management (D0-D7).

Study Record Dates

• First Submitted: June 7, 2018
• First Posted: June 29, 2018
• Study Start: July 5, 2018
• Primary Completion: December 16, 2020
• Study Completion: December 24, 2021
• Last Updated: April 6, 2022

Record last verified: 2022-04

Locations

GU (1); FR (58)