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

Sponsor

Nantes University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT03573739

Collaborator

Ministry of Health, France (Other), University Hospital, Tours (Other)

3,044

Enrollment

Locations

Arms

41.7

Actual Duration (Months)

51.6

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Critical Illness Shock Mechanical Ventilation Critical Illness Myopathy Nosocomial Infection	Procedure: low-calorie low-protein Procedure: standard-calorie/standard-protein	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

3044 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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).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).

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

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)

Actual Study Start Date :

Jul 5, 2018

Actual Primary Completion Date :

Dec 16, 2020

Actual Study Completion Date :

Dec 24, 2021

Arms and Interventions

Arm	Intervention/Treatment
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.

Arm

Intervention/Treatment

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.

Outcome Measures

Primary Outcome Measures

Time to discharge alive from the ICU. [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.
D-90 mortality [90 days]
All-cause mortality by day 90

Secondary Outcome Measures

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]
Ratio (as a %) of prescribed over calories delivered daily enterally and/or parenterally
Proportion of patients who achieved their calorie target [from day 0 to day 7]
Proportion of patients who achieved their calorie target
Protein supply [from day 0 to day 7]
Protein supply (g) given daily enterally and/or parenterally
Volume of fluids [from day 0 to day 7]
Volume of fluids (in mL) received daily
Changes in Sequential Organ Failure Assessment (SOFA) score [from day 0 to day 7]
SOFA scores can range from 0 (no organ failure) to 24 (most severe level of multi-organ failure).
Changes in daily maximum blood glucose levels [from day 0 to day 7]
Proportion of patients with hypoglycaemia [from day 0 to day 7]
insulin dose [from day 0 to day 7]
Total insulin dose received daily
insulin treatment [from day 0 to readiness for ICU discharge, an average of 10 days]
Days on insulin treatment
Proportion of patients with at least one ICU-acquired infection. [from day 0 to readiness for ICU discharge, an average of 10 days]
Proportion of patients with each type ICU-acquired infection [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).
Proportion of patients with at least one episode of vomiting or regurgitation while on mechanical ventilation [from day 0 to extubation, an average of 7 days]
Proportion of patients with at least one episode of liver dysfunction during follow-up [from day 0 to readiness for ICU discharge, an average of 10 days]
Proportion of patients with at least one episode of diarrhoea [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
Proportion of patients with at least one episode of constipation [from day 0 to extubation, an average of 7 days]
no stool for more than 6 days
Proportion of patients with at least one documented episode of bowel ischaemia [from day 0 to readiness for ICU discharge, an average of 10 days]
Mean changes in serum albumin [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
Mean changes in serum pre-albumin [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
Changes in serum C-reactive protein (CRP) [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
Changes in mean body weight [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
Hospital stay [from day 0 to hospital discharge, an average of 23 days]
Hospital stay length (days in hospital)
Duration of mechanical ventilation [from day 0 to extubation, an average of 7 days]
Days on mechanical ventilation
ICU mortality [from day 0 to ICU discharge, an average of 23 days]
Proportions of patients dead during the ICU stay
Mortality at day 28 [from day 0 to day 28]
Proportions of patients dead until day 28 after randomization
Hospital mortality [from day 0 to hospital discharge, an average of 23 days]
Proportions of patients dead during the hospital stay
Proportions of patients mobilized [from day 0 to day 7]
Evaluation of mobilisation during the ICU stay using predetermined criteria.
Total number of active mobilizations [from day 0 to day 7]
Evaluation of mobilisation during the ICU stay using predetermined criteria.
Muscle function [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).
Proportion of patients with at least one criterion for persistent altered health status [On the day of readiness for ICU discharge, an average of 10 days]
at the time of readiness for ICU discharge
SF-36 score [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chu de La Reunion Site Nord	St Denis	La Réunion	France	97405
2	Chu Amiens Picardie	Amiens		France	80054
3	CHU Angers	Angers		France	49100
4	Centre Hospitalier D'Angouleme	Angoulême		France	16959
5	Ch Annecy-Genevois	Annecy		France	74374
6	Centre Hospitalier D'Argenteuil	Argenteuil		France	95100
7	Hôpital du bois brulé	Beauvais		France	60000
8	Hôpital Nord Franche Comté	Belfort		France	90015
9	Chu Jean Minjoz	Besançon		France	25030
10	Hôpital Avicenne AP-HP	Bobigny		France	93000
11	Hopital Pellegrin Chu	Bordeaux		France	33000
12	CHU Cavale Blanche	Brest		France	29609
13	Hôpital de Béthune	Béthune		France	62408
14	Ch Chartres Louis Pasteur	Chartres		France	28630
15	Chu Gabriel Montpied	Clermont-Ferrand		France	63003
16	Hopital Louis Mourier (Ap-Hp)	Colombes		France	92701
17	Ch Dieppe	Dieppe		France	76202
18	Chu Bocage	Dijon		France	21079
19	Hôpital Raymond-Poincaré	Garches		France	92380
20	Hôpital Michalon	Grenoble		France	38043
21	Chd Les Oudairies	la Roche sur Yon		France	85025
22	Chu Bicetre	le kremlin Bicêtre		France	94270
23	Centre Hospitalier Du Mans	le Mans		France	72037
24	CH Emile Roux	Le Puy en Velay		France	43000
25	Centre Hospitalier de Lens	Lens		France	62300
26	Chr - Hopital Roger Salengro	Lille		France	59037
27	CH Saint-Philibert	Lomme		France	59462
28	Hopital de La Croix-Rousse	Lyon		France	69317
29	Hopital Edouard Herriot	Lyon		France	69437
30	Centre Hospitalier Marc Jacquet	Melun		France	77011
31	Centre Hospitalier de Montauban	Montauban		France	82013
32	Hopital Saint Eloi	Montpellier		France	34295
33	Ctre Hosp Intercomm Andre Gregoire	Montreuil		France	93100
34	Chu de Nantes	Nantes		France	44000
35	CHU Nantes	Nantes		France	44093
36	Chr D'Orleans	Orléans		France	86709
37	Hopital Lariboisiere	Paris		France	75010
38	Hôpital Saint Louis (AP-HP)	Paris		France	75010
39	Hopital Saint Antoine	Paris		France	75012
40	Hopital Pitie Salpetriere	Paris		France	75013
41	CHU Paris Cochin	Paris		France	75014
42	G.I.H. Bichat / Claude Bernard (Ap-Hp)	Paris		France	75877
43	Hopital Europeen Georges Pompidou	Paris		France	75908
44	CH Pau	Pau		France	64000
45	Chu La Miletrie	Poitiers		France	86021
46	C.H.R. Pontchaillou	Rennes		France	35033
47	C.H. de Rodez Hopital Jacques Puel	Rodez		France	12027
48	Hopital Charles Nicolle Chu Rouen	Rouen		France	76038
49	CH Saint Brieuc	Saint Brieuc		France	22000
50	CHU de Saint Etienne	Saint Priest en Jarez		France	42270
51	Ch General Delafontaine	Saint-Denis		France	93205
52	Hopital Broussais	Saint-Malo		France	35403
53	Hôpital de Hautepierre CHU de Strasbourg	Strasbourg		France	67098
54	Hopital Foch	Suresnes		France	92150
55	CH de Bigorre	Tarbes		France	65013
56	CHU DE TOURS Bretonneau	Tours		France	37044
57	CH Valenciennes	Valenciennes		France	59300
58	Centre Hospitalier Bretagne Atlantique - Vannes Auray	Vannes		France	56017
59	CHU Pointe à Pitre - Abymes	Pointe-à-pitre		Guadeloupe	97159

Sponsors and Collaborators

Nantes University Hospital
Ministry of Health, France
University Hospital, Tours

Investigators

Principal Investigator: Jean Reignier, MD, PhD, Nantes University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Nantes University Hospital

ClinicalTrials.gov Identifier:

NCT03573739

Other Study ID Numbers:

RC18_0006

First Posted:

Jun 29, 2018

Last Update Posted:

Apr 6, 2022

Last Verified:

Apr 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Cross Infection

Shock

Critical Illness

Study Results

No Results Posted as of Apr 6, 2022