Impact of an early extended rehabilitation programme combining individually tailored nutrition and physical activity on patient outcomes after invasive mechanical ventilation and vasopressor therapy in the ICU: design and conduct of a multicentre, randomised, controlled, open-label, assessor-blinded trial (NUTRIREA-4).

INTRODUCTION: Survivors of severe critical illness often experience long-lasting physical, quality of life and psychological impairments. Intensive care unit (ICU)-acquired weakness develops early and is associated with prolonged mechanical ventilation, delayed functional recovery, impaired quality of life and greater healthcare utilisation. Nutritional support and early mobilisation are considered key components of ICU care. However, trials have evaluated either nutritional or physical rehabilitation strategies and have not consistently demonstrated long-term benefits. A strong physiological rationale exists for combining nutritional therapy and structured physical rehabilitation. Moreover, most interventions were limited to the ICU stay. The NUTRIREA-4 trial will assess whether an individualised, integrated rehabilitation strategy of nutritional support, physiotherapy and adapted physical activity initiated early in the ICU and continued throughout and after the hospital stay improves long-term physical performance and recovery. NUTRIREA-4 is the first large-scale multicentre randomised controlled trial evaluating such a comprehensive approach in survivors of severe critical illness.

METHODS AND ANALYSIS: NUTRIREA-4 is a randomised controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasopressor therapy for shock and randomised to either an individualised rehabilitation programme or usual care. The rehabilitation programme combines goal-directed nutritional support, physiotherapy and adapted physical activity delivered from ICU admission to 12 weeks after the return home. We will include 830 patients in 52 French ICUs. The primary endpoint is the 6-minute walk distance measured by blinded assessors 6 months after randomisation. Secondary outcomes include muscle strength, physical activity, nutritional intake, ICU-acquired infections, quality of life, mortality and psychological recovery.

ETHICS AND DISSEMINATION: The NUTRIREA-4 trial has been approved by the appropriate ethics committee. Patients are included after informed consent according to French law. The results will be published in international peer-reviewed journals and presented at conferences.

TRIAL REGISTRATION NUMBER: NCT06581939.