Clinical trial NCT03573739: Impact of Early Low-Calorie Low-Protein Versus Standard Feeding on Outcomes of Ventilated Adults With Shock
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Critical Illness
Shock
Mechanical Ventilation
Critical Illness Myopathy
Nosocomial Infection
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
name: University Hospital, Tours
First posted: 2018-06-29
Enrollment: 3044
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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).
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Time to discharge alive from the ICU.
timeFrame: 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.
measure: D-90 mortality
timeFrame: 90 days
Secondary outcomes:
measure: Number of calories (in kcal) delivered daily enterally and/or parenterally
timeFrame: from day 0 to day 7
measure: Ratio of prescribed over calories delivered
timeFrame: from day 0 to day 7
measure: Proportion of patients who achieved their calorie target
timeFrame: from day 0 to day 7
measure: Protein supply
timeFrame: from day 0 to day 7
measure: Volume of fluids
timeFrame: from day 0 to day 7
measure: Changes in Sequential Organ Failure Assessment (SOFA) score
timeFrame: from day 0 to day 7
measure: Changes in daily maximum blood glucose levels
timeFrame: from day 0 to day 7
measure: Proportion of patients with hypoglycaemia
timeFrame: from day 0 to day 7
measure: insulin dose
timeFrame: from day 0 to day 7
measure: insulin treatment
timeFrame: from day 0 to readiness for ICU discharge, an average of 10 days
measure: Proportion of patients with at least one ICU-acquired infection.
timeFrame: from day 0 to readiness for ICU discharge, an average of 10 days
measure: Proportion of patients with each type ICU-acquired infection
timeFrame: from day 0 to readiness for ICU discharge, an average of 10 days
measure: Proportion of patients with at least one episode of vomiting or regurgitation while on mechanical ventilation
timeFrame: from day 0 to extubation, an average of 7 days
measure: Proportion of patients with at least one episode of liver dysfunction during follow-up
timeFrame: from day 0 to readiness for ICU discharge, an average of 10 days
measure: Proportion of patients with at least one episode of diarrhoea
timeFrame: from day 0 to extubation, an average of 7 days
measure: Proportion of patients with at least one episode of constipation
timeFrame: from day 0 to extubation, an average of 7 days
measure: Proportion of patients with at least one documented episode of bowel ischaemia
timeFrame: from day 0 to readiness for ICU discharge, an average of 10 days
measure: Mean changes in serum albumin
timeFrame: from day 0 to day 7 and readiness for ICU discharge, an average of 10 days
measure: Mean changes in serum pre-albumin
timeFrame: from day 0 to day 7 and readiness for ICU discharge, an average of 10 days
measure: Changes in serum C-reactive protein (CRP)
timeFrame: from day 0 to day 7 and readiness for ICU discharge, an average of 10 days
measure: Changes in mean body weight
timeFrame: from day 0 to day 7 and readiness for ICU discharge, an average of 10 days
measure: Hospital stay
timeFrame: from day 0 to hospital discharge, an average of 23 days
measure: Duration of mechanical ventilation
timeFrame: from day 0 to extubation, an average of 7 days
measure: ICU mortality
timeFrame: from day 0 to ICU discharge, an average of 23 days
measure: Mortality at day 28
timeFrame: from day 0 to day 28
measure: Hospital mortality
timeFrame: from day 0 to hospital discharge, an average of 23 days
measure: Proportions of patients mobilized
timeFrame: from day 0 to day 7
measure: Total number of active mobilizations
timeFrame: from day 0 to day 7
measure: Muscle function
timeFrame: On the day of readiness for ICU discharge, an average of 10 days
measure: Proportion of patients with at least one criterion for persistent altered health status
timeFrame: On the day of readiness for ICU discharge, an average of 10 days
measure: SF-36 score
timeFrame: 3 months and 1 year after study inclusion
Other outcomes:
Locations:
city: St Denis
country: France
facility: Chu de La Reunion Site Nord
state: La Réunion
city: Amiens
country: France
facility: Chu Amiens Picardie
city: Angers
country: France
facility: CHU Angers
city: Angoulême
country: France
facility: Centre Hospitalier D'Angouleme
city: Annecy
country: France
facility: Ch Annecy-Genevois
city: Argenteuil
country: France
facility: Centre Hospitalier D'Argenteuil
city: Beauvais
country: France
facility: Hôpital du bois brulé
city: Belfort
country: France
facility: Hôpital Nord Franche Comté
city: Besançon
country: France
facility: Chu Jean Minjoz
city: Bobigny
country: France
facility: Hôpital Avicenne AP-HP
city: Bordeaux
country: France
facility: Hopital Pellegrin Chu
city: Brest
country: France
facility: CHU Cavale Blanche
city: Béthune
country: France
facility: Hôpital de Béthune
city: Chartres
country: France
facility: Ch Chartres Louis Pasteur
city: Clermont-Ferrand
country: France
facility: Chu Gabriel Montpied
city: Colombes
country: France
facility: Hopital Louis Mourier (Ap-Hp)
city: Dieppe
country: France
facility: Ch Dieppe
city: Dijon
country: France
facility: Chu Bocage
city: Garches
country: France
facility: Hôpital Raymond-Poincaré
city: Grenoble
country: France
facility: Hôpital Michalon
city: la Roche sur Yon
country: France
facility: Chd Les Oudairies
city: le kremlin Bicêtre
country: France
facility: Chu Bicetre
city: le Mans
country: France
facility: Centre Hospitalier Du Mans
city: Le Puy en Velay
country: France
facility: CH Emile Roux
city: Lens
country: France
facility: Centre Hospitalier de Lens
city: Lille
country: France
facility: Chr - Hopital Roger Salengro
city: Lomme
country: France
facility: CH Saint-Philibert
city: Lyon
country: France
facility: Hopital de La Croix-Rousse
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Melun
country: France
facility: Centre Hospitalier Marc Jacquet
city: Montauban
country: France
facility: Centre Hospitalier de Montauban
city: Montpellier
country: France
facility: Hopital Saint Eloi
city: Montreuil
country: France
facility: Ctre Hosp Intercomm Andre Gregoire
city: Nantes
country: France
facility: Chu de Nantes
city: Nantes
country: France
facility: CHU Nantes
city: Orléans
country: France
facility: Chr D'Orleans
city: Paris
country: France
facility: Hopital Lariboisiere
city: Paris
country: France
facility: Hôpital Saint Louis (AP-HP)
city: Paris
country: France
facility: Hopital Saint Antoine
city: Paris
country: France
facility: Hopital Pitie Salpetriere
city: Paris
country: France
facility: CHU Paris Cochin
city: Paris
country: France
facility: G.I.H. Bichat / Claude Bernard (Ap-Hp)
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Pau
country: France
facility: CH Pau
city: Poitiers
country: France
facility: Chu La Miletrie
city: Rennes
country: France
facility: C.H.R. Pontchaillou
city: Rodez
country: France
facility: C.H. de Rodez Hopital Jacques Puel
city: Rouen
country: France
facility: Hopital Charles Nicolle Chu Rouen
city: Saint Brieuc
country: France
facility: CH Saint Brieuc
city: Saint Priest en Jarez
country: France
facility: CHU de Saint Etienne
city: Saint-Denis
country: France
facility: Ch General Delafontaine
city: Saint-Malo
country: France
facility: Hopital Broussais
city: Strasbourg
country: France
facility: Hôpital de Hautepierre CHU de Strasbourg
city: Suresnes
country: France
facility: Hopital Foch
city: Tarbes
country: France
facility: CH de Bigorre
city: Tours
country: France
facility: CHU DE TOURS Bretonneau
city: Valenciennes
country: France
facility: CH Valenciennes
city: Vannes
country: France
facility: Centre Hospitalier Bretagne Atlantique - Vannes Auray
city: Pointe-à-pitre
country: Guadeloupe
facility: CHU Pointe à Pitre - Abymes
Study officials:
affiliation: Nantes University Hospital
name: Jean Reignier, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.