Impact of Early Low-Calorie Low-Protein Versus Standard Feeding on Outcomes of Ventilated Adults With Shock (NUTRIREA3)

September 10, 2026 updated by: Nantes University Hospital

Impact of Early Low-Calorie Low-Protein Versus Standard-Calorie Standard-Protein Feeding on Outcomes of Ventilated Adults With Shock: a Randomised, Controlled, Multicentre, Open-label, Parallel-group Study (NUTRIREA-3)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
3044

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Amiens, France, 80054
        • CHU Amiens Picardie
      • Angers, France, 49100
        • CHU Angers
      • Angoulême, France, 16959
        • Centre Hospitalier D'Angouleme
      • Annecy, France, 74374
        • Ch Annecy-Genevois
      • Argenteuil, France, 95100
        • Centre Hospitalier d'Argenteuil
      • Beauvais, France, 60000
        • Hôpital du bois brulé
      • Belfort, France, 90015
        • Hôpital Nord Franche Comté
      • Besançon, France, 25030
        • Chu Jean Minjoz
      • Bobigny, France, 93000
        • Hôpital Avicenne AP-HP
      • Bordeaux, France, 33000
        • Hopital Pellegrin Chu
      • Brest, France, 29609
        • CHU Cavale Blanche
      • Béthune, France, 62408
        • Hôpital de Béthune
      • Chartres, France, 28630
        • Ch Chartres Louis Pasteur
      • Clermont-Ferrand, France, 63003
        • Chu Gabriel Montpied
      • Colombes, France, 92701
        • Hopital Louis Mourier (Ap-Hp)
      • Dieppe, France, 76202
        • Ch Dieppe
      • Dijon, France, 21079
        • CHU Bocage
      • Garches, France, 92380
        • Hôpital Raymond-Poincaré
      • Grenoble, France, 38043
        • Hôpital Michalon
      • La Roche-sur-Yon, France, 85025
        • CHD les Oudairies
      • Le Kremlin-Bicêtre, France, 94270
        • Chu Bicetre
      • Le Mans, France, 72037
        • Centre Hospitalier du Mans
      • Le Puy-en-Velay, France, 43000
        • CH Emile Roux
      • Lens, France, 62300
        • Centre Hospitalier de Lens
      • Lille, France, 59037
        • Chr - Hopital Roger Salengro
      • Lomme, France, 59462
        • CH Saint-Philibert
      • Lyon, France, 69437
        • Hôpital Edouard Herriot
      • Lyon, France, 69317
        • Hôpital de la Croix-Rousse
      • Melun, France, 77011
        • Centre Hospitalier Marc Jacquet
      • Montauban, France, 82013
        • Centre Hospitalier de Montauban
      • Montpellier, France, 34295
        • Hopital Saint Eloi
      • Montreuil, France, 93100
        • Ctre Hosp Intercomm Andre Gregoire
      • Nantes, France, 44093
        • CHU Nantes
      • Nantes, France, 44000
        • CHU de Nantes
      • Orléans, France, 86709
        • CHR d'Orléans
      • Paris, France, 75010
        • Hôpital Lariboisière
      • Paris, France, 75012
        • Hopital Saint Antoine
      • Paris, France, 75010
        • Hôpital Saint Louis (AP-HP)
      • Paris, France, 75013
        • Hôpital Pitie Salpétrière
      • Paris, France, 75014
        • CHU Paris Cochin
      • Paris, France, 75877
        • G.I.H. Bichat / Claude Bernard (Ap-Hp)
      • Paris, France, 75908
        • Hôpital Europeén Georges Pompidou
      • Pau, France, 64000
        • CH Pau
      • Poitiers, France, 86021
        • CHU La Miletrie
      • Rennes, France, 35033
        • C.H.R. Pontchaillou
      • Rodez, France, 12027
        • C.H. de Rodez Hopital Jacques Puel
      • Rouen, France, 76038
        • Hopital Charles Nicolle Chu Rouen
      • Saint-Brieuc, France, 22000
        • CH Saint Brieuc
      • Saint-Denis, France, 93205
        • Ch General Delafontaine
      • Saint-Priest-en-Jarez, France, 42270
        • CHU de Saint Etienne
      • St-Malo, France, 35403
        • Hopital Broussais
      • Strasbourg, France, 67098
        • Hôpital de Hautepierre CHU de Strasbourg
      • Suresnes, France, 92150
        • Hôpital Foch
      • Tarbes, France, 65013
        • CH de Bigorre
      • Tours, France, 37044
        • CHU DE TOURS Bretonneau
      • Valenciennes, France, 59300
        • CH Valenciennes
      • Vannes, France, 56017
        • Centre Hospitalier Bretagne Atlantique - Vannes Auray
    • La Réunion
      • Saint-Denis, La Réunion, France, 97405
        • Chu de La Reunion Site Nord
  • Guadeloupe
      • Pointe-à-Pitre, Guadeloupe, 97159
        • CHU Pointe à Pitre - Abymes

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Low group
Patients randomized in the "low group" will receive a low-calorie low-protein nutrition regimen during the acute phase.
Procedure: 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.
Active Comparator: Standard group
Patients randomized in the "standard group" will receive a standard-calorie/standard-protein nutrition regimen during the acute phase.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time to discharge alive from the ICU.
Time Frame: 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.
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
Time Frame: 90 days
All-cause mortality by day 90
90 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of calories (in kcal) delivered daily enterally and/or parenterally
Time Frame: from day 0 to day 7
from day 0 to day 7
Ratio of prescribed over calories delivered
Time Frame: from day 0 to day 7
Ratio (as a %) of prescribed over calories delivered daily enterally and/or parenterally
from day 0 to day 7
Proportion of patients who achieved their calorie target
Time Frame: from day 0 to day 7
Proportion of patients who achieved their calorie target
from day 0 to day 7
Protein supply
Time Frame: from day 0 to day 7
Protein supply (g) given daily enterally and/or parenterally
from day 0 to day 7
Volume of fluids
Time Frame: from day 0 to day 7
Volume of fluids (in mL) received daily
from day 0 to day 7
Changes in Sequential Organ Failure Assessment (SOFA) score
Time Frame: from day 0 to day 7
SOFA scores can range from 0 (no organ failure) to 24 (most severe level of multi-organ failure).
from day 0 to day 7
Changes in daily maximum blood glucose levels
Time Frame: from day 0 to day 7
from day 0 to day 7
Proportion of patients with hypoglycaemia
Time Frame: from day 0 to day 7
from day 0 to day 7
insulin dose
Time Frame: from day 0 to day 7
Total insulin dose received daily
from day 0 to day 7
insulin treatment
Time Frame: from day 0 to readiness for ICU discharge, an average of 10 days
Days on insulin treatment
from day 0 to readiness for ICU discharge, an average of 10 days
Proportion of patients with at least one ICU-acquired infection.
Time Frame: from day 0 to readiness for ICU discharge, an average of 10 days
from day 0 to readiness for ICU discharge, an average of 10 days
Proportion of patients with each type ICU-acquired infection
Time Frame: from day 0 to readiness for ICU discharge, an average of 10 days
e.g. (Ventilator-associated pneumonia, bacteremia, Central venous catheter-related infections, Urinary tract infections, soft tissue infections).
from day 0 to readiness for ICU discharge, an average of 10 days
Proportion of patients with at least one episode of vomiting or regurgitation while on mechanical ventilation
Time Frame: from day 0 to extubation, an average of 7 days
from day 0 to extubation, an average of 7 days
Proportion of patients with at least one episode of liver dysfunction during follow-up
Time Frame: from day 0 to readiness for ICU discharge, an average of 10 days
from day 0 to readiness for ICU discharge, an average of 10 days
Proportion of patients with at least one episode of diarrhoea
Time Frame: from day 0 to extubation, an average of 7 days
defined as liquid stools in a volume greater than 300 mL/24 hours in patients with a faecal collector or as more than four loose stools/24 hours
from day 0 to extubation, an average of 7 days
Proportion of patients with at least one episode of constipation
Time Frame: from day 0 to extubation, an average of 7 days
no stool for more than 6 days
from day 0 to extubation, an average of 7 days
Proportion of patients with at least one documented episode of bowel ischaemia
Time Frame: from day 0 to readiness for ICU discharge, an average of 10 days
from day 0 to readiness for ICU discharge, an average of 10 days
Mean changes in serum albumin
Time Frame: from day 0 to day 7 and readiness for ICU discharge, an average of 10 days
measured at baseline, at the end of mechanical ventilation, on day 7 (in patients on mechanical ventilation for more than 7 days), and at ICU discharge
from day 0 to day 7 and readiness for ICU discharge, an average of 10 days
Mean changes in serum pre-albumin
Time Frame: from day 0 to day 7 and readiness for ICU discharge, an average of 10 days
measured at baseline, at the end of mechanical ventilation, on day 7 (in patients on mechanical ventilation for more than 7 days), and at ICU discharge
from day 0 to day 7 and readiness for ICU discharge, an average of 10 days
Changes in serum C-reactive protein (CRP)
Time Frame: from day 0 to day 7 and readiness for ICU discharge, an average of 10 days
measured at baseline, at the end of mechanical ventilation, on day 7 (in patients on mechanical ventilation for more than 7 days), and at ICU discharge
from day 0 to day 7 and readiness for ICU discharge, an average of 10 days
Changes in mean body weight
Time Frame: from day 0 to day 7 and readiness for ICU discharge, an average of 10 days
determined at baseline, on day 7, and at ICU discharge
from day 0 to day 7 and readiness for ICU discharge, an average of 10 days
Hospital stay
Time Frame: from day 0 to hospital discharge, an average of 23 days
Hospital stay length (days in hospital)
from day 0 to hospital discharge, an average of 23 days
Duration of mechanical ventilation
Time Frame: from day 0 to extubation, an average of 7 days
Days on mechanical ventilation
from day 0 to extubation, an average of 7 days
ICU mortality
Time Frame: from day 0 to ICU discharge, an average of 23 days
Proportions of patients dead during the ICU stay
from day 0 to ICU discharge, an average of 23 days
Mortality at day 28
Time Frame: from day 0 to day 28
Proportions of patients dead until day 28 after randomization
from day 0 to day 28
Hospital mortality
Time Frame: from day 0 to hospital discharge, an average of 23 days
Proportions of patients dead during the hospital stay
from day 0 to hospital discharge, an average of 23 days
Proportions of patients mobilized
Time Frame: from day 0 to day 7
Evaluation of mobilisation during the ICU stay using predetermined criteria.
from day 0 to day 7
Total number of active mobilizations
Time Frame: from day 0 to day 7
Evaluation of mobilisation during the ICU stay using predetermined criteria.
from day 0 to day 7
Muscle function
Time Frame: On the day of readiness for ICU discharge, an average of 10 days
Muscle function at the time of readiness for ICU discharge as assessed with the Medical Research Council (MRC) score. The MRC score ranges from 0 (no muscle activity) to 60 (normal muscle function).
On the day of readiness for ICU discharge, an average of 10 days
Proportion of patients with at least one criterion for persistent altered health status
Time Frame: On the day of readiness for ICU discharge, an average of 10 days
at the time of readiness for ICU discharge
On the day of readiness for ICU discharge, an average of 10 days
SF-36 score
Time Frame: 3 months and 1 year after study inclusion
The Short Form (SF)-36 is a multipurpose health survey with 36 questions. Questionnaires will be completed during a phone call to the patient by an independent blinded research nurse or psychologist.
3 months and 1 year after study inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Nantes University Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Ministry of Health, France
University Hospital, Tours

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jean Reignier, MD, PhD, Nantes university hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 5, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 16, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 24, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 7, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 28, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 29, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 14, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 10, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RC18_0006

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings