Impact of an Early and Extended Rehabilitation Program Combining Individually Tailored Nutrition and Physical Activities on Patient Outcomes After Invasive Mechanical Ventilation and Vasopressor Therapy in the ICU (NUTRIREA-4)

January 22, 2026 updated by: Nantes University Hospital

Impact of an Early and Extended Rehabilitation Program Combining Individually Tailored Nutrition and Physical Activities on Patient Outcomes After Invasive Mechanical Ventilation and Vasopressor Therapy in the ICU : A Multicenter Randomized Controlled Trial

The NUTRIREA-4 trial will test the hypothesis that an individually tailored rehabilitation program combining nutritional therapy, physiotherapy, and physical activity and started early in the ICU then continued uninterruptedly throughout the post-ICU stay and at home after hospital discharge improves the long-term outcomes of critical-illness survivors, compared to usual care.

From ICU admission to recovery at home, the trial patients will receive either usual care or the early extended rehabilitation program. Usual care will consist in nutritional support and physiotherapy according to usual local practice in each participating ICU. The early extended program will consist of nutritional therapy, physiotherapy, and physical activity according to a standardized protocol tailored to general- and muscle-health improvements achieved in each individual patient over time.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

830

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Invasive mechanical ventilation (MV) started in the ICU within the past 24 h, or started before ICU admission with ICU admission within the past 24 h, and expected to be required for at least 48 hours after randomization
  • 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 if intubation occurred before ICU admission)
  • Age 18 or older
  • Patient and/or next-of-kin informed about the trial and having consented to participation in the trial. If the patient is unable to receive information and no next-of-kin can be contacted during screening for the trial, trial inclusion will be completed as an emergency procedure by the ICU physician, in compliance with French law.
  • Covered by the French public health-insurance system

Exclusion Criteria:

  • MV started more than 24 hours earlier
  • Specific nutritional needs, such as pre-existing long-term home enteral or parenteral nutrition for chronic bowel disease
  • Dying patient, do-not-resuscitate order, or other treatment- limitation decision at ICU admission
  • Social circumstances hindering follow-up and telephone/video consultations (no fixed address, non-European residence)
  • Inability to provide a stable personal mobile phone number (temporary number or not in the owner's name)
  • Communication difficulties via telephone or video consultation (pre-existing severe hearing or visual impairment)
  • Pre-existing chronic illness with life expectancy <6 months
  • Pre-existing cognitive impairment
  • Pre-existing spinal injury
  • Inability to walk before the critical illness
  • Acute or chronic neuromuscular disease
  • Brain injury, e.g., due to cardiac arrest, stroke, or severe trauma
  • Pregnancy, recent delivery, or lactation
  • Adult under guardianship
  • Correctional facility inmate
  • Institutionalized patient
  • Prior inclusion in a randomized trial designed to compare rehabilitation programs delivered to patients during critical illness

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Control group
Usual care
Procedure: Control group
In the control group, patients will receive usual care from day-0 to day-180.
Experimental: Rehabilitation group
Individualized rehabilitation program
Procedure: Rehabilitation group
In the rehabilitation group, patients will follow an individualized rehabilitation program started early in the ICU and continued in the post-ICU ward then at home for 12 weeks, combining goal-directed nutrition and physical activity, tailored to gains made over time by each patient, with the involvement of dieticians, physiotherapists, and adapted-physical-activity instructors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
6-minute-walk distance
Time Frame: 6 months
The primary endpoint is the 6-minute-walk distance (6MWD), in meters, assessed by blinded physicians and research nurses during a hospital visit 6 months after randomization.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Handgrip strength
Time Frame: 6 months after randomization
Handgrip strength (Kg and percent of predicted strength) at 6 months after randomization
6 months after randomization
Medical Research Council (MRC) score
Time Frame: 6 months after randomization
MRC score at 6 months after randomization
6 months after randomization
Muscle mass assessed by the mid-arm muscle circumference (MAMC)
Time Frame: 6 months after randomization
MAMC at 6 months after randomization
6 months after randomization
Physical activity assessed by the International Physical Activity Questionnaire Short Form (IPAQ-SF)
Time Frame: 3 months after randomization
IPAQ-SF score at 3 months after randomization
3 months after randomization
Physical activity assessed by the International Physical Activity Questionnaire Short Form (IPAQ-SF)
Time Frame: 4 months after randomization
IPAQ-SF score at 4 months after randomization
4 months after randomization
Physical activity assessed by the International Physical Activity Questionnaire Short Form (IPAQ-SF)
Time Frame: 5 months after randomization
IPAQ-SF score at 5 months after randomization
5 months after randomization
Physical activity assessed by the International Physical Activity Questionnaire Short Form (IPAQ-SF)
Time Frame: 6 months after randomization
IPAQ-SF score at 6 months after randomization
6 months after randomization
Physical activity assessed by the International Physical Activity Questionnaire Short Form (IPAQ-SF)
Time Frame: 12 months after randomization
IPAQ-SF score at 12 months after randomization
12 months after randomization
Calorie intakes
Time Frame: From day 0 to 12 months
Calorie intakes (daily mean during the hospital stay and at home at D90, D120, D150, D180, and one year after randomization)
From day 0 to 12 months
Protein intakes
Time Frame: From day 0 to 12 months
Protein intakes (daily mean during the hospital stay and at home at D90, D120, D150, D180, and one year after randomization)
From day 0 to 12 months
Body weight
Time Frame: 6 months
Mean changes in body weight measured at 6 months)
6 months
Mortality rates
Time Frame: Day 90
90-day mortality rates
Day 90
Mortality rates
Time Frame: 6 months
6-month mortality rates
6 months
Mortality rates
Time Frame: 12 months
12-months mortality rates
12 months
Hypoglycemia
Time Frame: From day 0 to day 7
Proportion of patients with at least one hypoglycemia from day 0 to day 7
From day 0 to day 7
Blood glucose
Time Frame: From day 0 to day 7
Mean blood glucose from day 0 to day 7
From day 0 to day 7
Quality of life assessed using the Short Form 36 Health Survey (SF-36)
Time Frame: 6 and 12 months
SF-36 scores 6 and 12 months after randomization
6 and 12 months
Handgrip strength
Time Frame: ICU discharge, an average of 10 days
Handgrip strength (Kg and percent of predicted strength) at ICU discharge
ICU discharge, an average of 10 days
Handgrip strength
Time Frame: Hospital discharge, an average of 20 days
Handgrip strength (Kg and percent of predicted strength) at hospital discharge
Hospital discharge, an average of 20 days
Medical Research Council (MRC) score
Time Frame: ICU discharge, an average of 10 days
MRC score at ICU discharge
ICU discharge, an average of 10 days
Medical Research Council (MRC) score
Time Frame: Hospital discharge, an average of 20 days
MRC score at hospital discharge
Hospital discharge, an average of 20 days
Muscle mass assessed by the mid-arm muscle circumference (MAMC)
Time Frame: ICU discharge, an average of 10 days
MAMC at ICU discharge
ICU discharge, an average of 10 days
Muscle mass assessed by the mid-arm muscle circumference (MAMC)
Time Frame: Hospital discharge, an average of 20 days
MAMC at hospital discharge
Hospital discharge, an average of 20 days
Body weight
Time Frame: ICU discharge, an average of 10 days
Mean changes in body weight measured at ICU discharge
ICU discharge, an average of 10 days
Mortality rates
Time Frame: ICU discharge, an average of 10 days
ICU discharge mortality rates
ICU discharge, an average of 10 days
Mechanical Ventilation (MV) duration
Time Frame: From D0 until the date of cessation of mechanical ventilation, an average of 7 days
Days of MV
From D0 until the date of cessation of mechanical ventilation, an average of 7 days
ICU-acquired infection
Time Frame: From day 0 until the date of discharge from ICU, an average of 10 days
Proportion of patients with at least one ICU-acquired infection
From day 0 until the date of discharge from ICU, an average of 10 days
ICU and hospital stay lengths
Time Frame: From day 0 until the day of discharge from hospital, an average of 20 days
ICU and hospital stay lengths (days)
From day 0 until the day of discharge from hospital, an average of 20 days
Mortality rates
Time Frame: Hospital discharge, an average of 20 days
Hospital discharge mortality rates
Hospital discharge, an average of 20 days
Insulin
Time Frame: From day 0 until the date of ICU discharge, an average of 10 days
Days on insulin in the ICU
From day 0 until the date of ICU discharge, an average of 10 days
Delay from randomization to first standing-up
Time Frame: From date of randomization until the date of first standing-up, an average of 7 days
Delay from randomization to first standing-up (days)
From date of randomization until the date of first standing-up, an average of 7 days
Delay from randomization to first walking
Time Frame: From date of randomization until the date of first walking, an average of 15 days
Delay from randomization to first walking (days)
From date of randomization until the date of first walking, an average of 15 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hospital Anxiety and Depression Scale (HADS)
Time Frame: 6 and 12 months
HADS score 6 and 12 months after randomization
6 and 12 months
Post-traumatic stress disorder Check List for DSM-5 (PCL-5)
Time Frame: 6 and 12 months
PCL-5 score 6 and 12 months after randomization
6 and 12 months
Posttraumatic growth using the Posttraumatic Growth Inventory Short Form (PTGI-SF)
Time Frame: 6 and 12 months
PTGI-SF 6 and 12 months after randomization
6 and 12 months
Cognitive performance using the Montreal Cognitive Assessment (MoCA)
Time Frame: 6 and 12 months
MoCA 6 and 12 months after randomization
6 and 12 months
Resilience assessed using the Connor-Davidson Resilience Scale (CD-RISC10)
Time Frame: 6 and 12 months
CD-RISC-10 6 and 12 months after randomization
6 and 12 months
Qualitative assessment on how the rehabilitation program influences resilience and psychological recovery after ICU
Time Frame: 12 months
Semi-structured interviews
12 months
Time course of circulating Growth-differentiation factor-15 (GDF-15)
Time Frame: Inclusion, H24, H72, Day 7, ICU discharge, Day 180
GDF-15 plasma level
Inclusion, H24, H72, Day 7, ICU discharge, Day 180
Effects of the individualized rehabilitation program, compared to usual care, on IFN-γ
Time Frame: Inclusion, H24, H72, Day7, ICU discharge, Day 180
IFN-γ plasma level
Inclusion, H24, H72, Day7, ICU discharge, Day 180
Effects of the individualized rehabilitation program, compared to usual care, on IFN-γ
Time Frame: Inclusion, H24, H72, Day7, ICU discharge, Day 180.
IL-1β plasma level
Inclusion, H24, H72, Day7, ICU discharge, Day 180.
Effects of the individualized rehabilitation program, compared to usual care, on IL-6
Time Frame: Inclusion, H24, H72, Day7, ICU discharge, Day 180
IL-6 plasma level
Inclusion, H24, H72, Day7, ICU discharge, Day 180
Effects of the individualized rehabilitation program, compared to usual care, on TNF-α
Time Frame: Inclusion, H24, H72, Day7, ICU discharge, Day 180
TNF-α plasma level
Inclusion, H24, H72, Day7, ICU discharge, Day 180
Effects of the individualized rehabilitation program, compared to usual care, on FGF-21
Time Frame: Inclusion, H24, H72, Day7, ICU discharge, Day 180
FGF-21 plasma level
Inclusion, H24, H72, Day7, ICU discharge, Day 180
Effects of the individualized rehabilitation program, compared to usual care, on leptin
Time Frame: Inclusion, H24, H72, Day7, ICU discharge, Day 180
leptin plasma level
Inclusion, H24, H72, Day7, ICU discharge, Day 180
Effects of the individualized rehabilitation program, compared to usual care, on C-peptide
Time Frame: inclusion, H24, H72, Day7, ICU discharge, Day 180
C-peptide plasma level
inclusion, H24, H72, Day7, ICU discharge, Day 180
Effects of the individualized rehabilitation program, compared to usual care, on Ghrelin
Time Frame: Inclusion, H24, H72, Day7, ICU discharge, Day 180
Ghrelin plasma level
Inclusion, H24, H72, Day7, ICU discharge, Day 180

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nantes University Hospital

Investigators

  • Principal Investigator: Jean REIGNIER, MD, PhD, Nantes University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 14, 2024

Primary Completion (Estimated)

June 14, 2027

Study Completion (Estimated)

December 14, 2027

Study Registration Dates

First Submitted

August 20, 2024

First Submitted That Met QC Criteria

August 29, 2024

First Posted (Actual)

September 3, 2024

Study Record Updates

Last Update Posted (Actual)

January 23, 2026

Last Update Submitted That Met QC Criteria

January 22, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC23_0585

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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