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

Not Applicable

Completed

• Conditions: Shock; Critical Illness Myopathy; Nosocomial Infection; Mechanical Ventilation; Critical Illness
• Interventions: Procedure: standard-calorie/standard-protein; Procedure: low-calorie low-protein

• Registration Number: NCT03573739
• Lead Sponsor: Nantes University Hospital

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-06-07
• Study First Submitted QC: 2018-06-28
• Study First Posted: 2018-06-29
• Study Start: 2018-07-05
• Primary Completion: 2020-12-16
• Study Completion: 2021-12-24
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-05
• Last Update Posted: 2022-04-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3044

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard group	standard-calorie/standard-protein	Patients randomized in the "standard group" will receive a standard-calorie/standard-protein nutrition regimen during the acute phase.
Low group	low-calorie low-protein	Patients randomized in the "low group" will receive a low-calorie low-protein nutrition regimen during the acute phase.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Volume of fluids	from day 0 to day 7	Volume of fluids (in mL) received daily
Number of calories (in kcal) delivered daily enterally and/or parenterally	from day 0 to day 7
Protein supply	from day 0 to day 7	Protein supply (g) given daily enterally and/or parenterally
Changes in daily maximum blood glucose levels	from day 0 to day 7
Proportion of patients with hypoglycaemia	from day 0 to day 7
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
insulin treatment	from day 0 to readiness for ICU discharge, an average of 10 days	Days on insulin treatment
Hospital stay	from day 0 to hospital discharge, an average of 23 days	Hospital stay length (days in hospital)
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
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).
insulin dose	from day 0 to day 7	Total insulin dose received daily
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 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 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 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 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).
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
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.

Trial Locations

Locations (59)

Chu de La Reunion Site Nord; 🇫🇷 St Denis, La Réunion, France

CHU Angers; 🇫🇷 Angers, France

Ch Chartres Louis Pasteur; 🇫🇷 Chartres, France

Ch Annecy-Genevois; 🇫🇷 Annecy, France

Hôpital Michalon; 🇫🇷 Grenoble, France

Chr - Hopital Roger Salengro; 🇫🇷 Lille, France

CHU Cavale Blanche; 🇫🇷 Brest, France

CH Saint Brieuc; 🇫🇷 Saint Brieuc, France

Ch General Delafontaine; 🇫🇷 Saint-Denis, France

CH Valenciennes; 🇫🇷 Valenciennes, France

Centre Hospitalier Bretagne Atlantique - Vannes Auray; 🇫🇷 Vannes, France

Centre Hospitalier D'Angouleme; 🇫🇷 Angoulême, France

Hopital Pellegrin Chu; 🇫🇷 Bordeaux, France

Hopital Louis Mourier (Ap-Hp); 🇫🇷 Colombes, France

Ch Dieppe; 🇫🇷 Dieppe, France

Hôpital Raymond-Poincaré; 🇫🇷 Garches, France

Centre Hospitalier de Lens; 🇫🇷 Lens, France

Chu Gabriel Montpied; 🇫🇷 Clermont-Ferrand, France

Centre Hospitalier Du Mans; 🇫🇷 le Mans, France

Hopital Saint Eloi; 🇫🇷 Montpellier, France

CHU Nantes; 🇫🇷 Nantes, France

Hopital Charles Nicolle Chu Rouen; 🇫🇷 Rouen, France

Hopital Foch; 🇫🇷 Suresnes, France

Chu Bocage; 🇫🇷 Dijon, France

Chr D'Orleans; 🇫🇷 Orléans, France

Chu La Miletrie; 🇫🇷 Poitiers, France

Hopital Edouard Herriot; 🇫🇷 Lyon, France

CHU Pointe à Pitre - Abymes; 🇬🇵 Pointe-à-pitre, Guadeloupe

G.I.H. Bichat / Claude Bernard (Ap-Hp); 🇫🇷 Paris, France

CHU de Saint Etienne; 🇫🇷 Saint Priest en Jarez, France

CH Saint-Philibert; 🇫🇷 Lomme, France

Centre Hospitalier Marc Jacquet; 🇫🇷 Melun, France

Chu Amiens Picardie; 🇫🇷 Amiens, France

Hôpital du bois brulé; 🇫🇷 Beauvais, France

Chu Jean Minjoz; 🇫🇷 Besançon, France

Centre Hospitalier D'Argenteuil; 🇫🇷 Argenteuil, France

Hôpital Avicenne AP-HP; 🇫🇷 Bobigny, France

Hôpital Nord Franche Comté; 🇫🇷 Belfort, France

Hôpital de Béthune; 🇫🇷 Béthune, France

Chd Les Oudairies; 🇫🇷 la Roche sur Yon, France

Chu Bicetre; 🇫🇷 le kremlin Bicêtre, France

CH Emile Roux; 🇫🇷 Le Puy en Velay, France

Hopital de La Croix-Rousse; 🇫🇷 Lyon, France

Centre Hospitalier de Montauban; 🇫🇷 Montauban, France

Ctre Hosp Intercomm Andre Gregoire; 🇫🇷 Montreuil, France

Chu de Nantes; 🇫🇷 Nantes, France

Hôpital Saint Louis (AP-HP); 🇫🇷 Paris, France

Hopital Lariboisiere; 🇫🇷 Paris, France

Hopital Saint Antoine; 🇫🇷 Paris, France

CHU Paris Cochin; 🇫🇷 Paris, France

Hopital Pitie Salpetriere; 🇫🇷 Paris, France

Hopital Europeen Georges Pompidou; 🇫🇷 Paris, France

CH Pau; 🇫🇷 Pau, France

C.H.R. Pontchaillou; 🇫🇷 Rennes, France

C.H. de Rodez Hopital Jacques Puel; 🇫🇷 Rodez, France

Hôpital de Hautepierre CHU de Strasbourg; 🇫🇷 Strasbourg, France

Hopital Broussais; 🇫🇷 Saint-Malo, France

CH de Bigorre; 🇫🇷 Tarbes, France

CHU DE TOURS Bretonneau; 🇫🇷 Tours, France