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.

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