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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03573739
Other study ID # RC18_0006
Secondary ID
Status Completed
Phase N/A
First received
Last updated
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
Health authority
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

Study Design


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
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