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

Critical Illness Clinical Trial

— NUTRIREA3  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03573739
• Other study ID #: RC18_0006
• Status: Completed
• Phase: N/A
• Start date: July 5, 2018
• Est. completion date: December 24, 2021

Study information

• Verified date: April 2022
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3044
• Est. completion date: December 24, 2021
• Est. primary completion date: December 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Critical Illness Myopathy
• Cross Infection
• Mechanical Ventilation
• Nosocomial Infection
• Shock

Intervention

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.
• 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.

Locations

Country	Name	City	State
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	CHU Paris Cochin	Paris
France	G.I.H. Bichat / Claude Bernard (Ap-Hp)	Paris
France	Hopital Europeen Georges Pompidou	Paris
France	Hopital Lariboisiere	Paris
France	Hopital Pitie Salpetriere	Paris
France	Hopital Saint Antoine	Paris
France	Hôpital Saint Louis (AP-HP)	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	CHU de Saint Etienne	Saint Priest en Jarez
France	Ch General Delafontaine	Saint-Denis
France	Hopital Broussais	Saint-Malo
France	Chu de La Reunion Site Nord	St Denis	La Réunion
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
Guadeloupe	CHU Pointe à Pitre - Abymes	Pointe-à-pitre

Sponsors (3)

Lead Sponsor	Collaborator
Nantes University Hospital	Ministry of Health, France, University Hospital, Tours

Countries where clinical trial is conducted

France,  Guadeloupe, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	D-90 mortality	All-cause mortality by day 90	90 days
Secondary	Number of calories (in kcal) delivered daily enterally and/or parenterally		from day 0 to day 7
Secondary	Ratio of prescribed over calories delivered	Ratio (as a %) of prescribed over calories delivered daily enterally and/or parenterally	from day 0 to day 7
Secondary	Proportion of patients who achieved their calorie target	Proportion of patients who achieved their calorie target	from day 0 to day 7
Secondary	Protein supply	Protein supply (g) given daily enterally and/or parenterally	from day 0 to day 7
Secondary	Volume of fluids	Volume of fluids (in mL) received daily	from day 0 to day 7
Secondary	Changes in Sequential Organ Failure Assessment (SOFA) score	SOFA scores can range from 0 (no organ failure) to 24 (most severe level of multi-organ failure).	from day 0 to day 7
Secondary	Changes in daily maximum blood glucose levels		from day 0 to day 7
Secondary	Proportion of patients with hypoglycaemia		from day 0 to day 7
Secondary	insulin dose	Total insulin dose received daily	from day 0 to day 7
Secondary	insulin treatment	Days on insulin treatment	from day 0 to readiness for ICU discharge, an average of 10 days
Secondary	Proportion of patients with at least one ICU-acquired infection.		from day 0 to readiness for ICU discharge, an average of 10 days
Secondary	Proportion of patients with each type ICU-acquired infection	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
Secondary	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
Secondary	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
Secondary	Proportion of patients with at least one episode of diarrhoea	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
Secondary	Proportion of patients with at least one episode of constipation	no stool for more than 6 days	from day 0 to extubation, an average of 7 days
Secondary	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
Secondary	Mean changes in serum albumin	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
Secondary	Mean changes in serum pre-albumin	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
Secondary	Changes in serum C-reactive protein (CRP)	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
Secondary	Changes in mean body weight	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
Secondary	Hospital stay	Hospital stay length (days in hospital)	from day 0 to hospital discharge, an average of 23 days
Secondary	Duration of mechanical ventilation	Days on mechanical ventilation	from day 0 to extubation, an average of 7 days
Secondary	ICU mortality	Proportions of patients dead during the ICU stay	from day 0 to ICU discharge, an average of 23 days
Secondary	Mortality at day 28	Proportions of patients dead until day 28 after randomization	from day 0 to day 28
Secondary	Hospital mortality	Proportions of patients dead during the hospital stay	from day 0 to hospital discharge, an average of 23 days
Secondary	Proportions of patients mobilized	Evaluation of mobilisation during the ICU stay using predetermined criteria.	from day 0 to day 7
Secondary	Total number of active mobilizations	Evaluation of mobilisation during the ICU stay using predetermined criteria.	from day 0 to day 7
Secondary	Muscle function	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
Secondary	Proportion of patients with at least one criterion for persistent altered health status	at the time of readiness for ICU discharge	On the day of readiness for ICU discharge, an average of 10 days
Secondary	SF-36 score	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