Nutrition and Exercise in Critical Illness (NEXIS) trial: randomized trial of combined in-bed cycling and intravenous amino acid plus usual care

RATIONALE: Patients with acute respiratory failure (ARF) in intensive care units (ICUs) often experience immobility and limited nutritional intake, with long-lasting impairments. OBJECTIVE: Evaluate whether combined in-bed cycling exercise and intravenous amino acid, initiated early in the ICU, improves physical functioning. METHODS: This multicenter phase 2 trial randomly allocated patients 1:1 to protocolized in-bed cycling (45 min/d) plus intravenous amino acid (total protein intake: 2.0-2.5 g/kg/d) plus usual care vs usual care alone. Blinded assessment of 6-minute walk distance (6MWD) at hospital discharge was the primary outcome. Secondary outcomes included functional measures at ICU and hospital discharge, along with phone surveys at the 6-month follow-up. Patients were analyzed according to intention to treat. The planned sample size was 128 evaluable patients (64 per arm). MEASUREMENTS AND MAIN RESULTS: In total, 115 patients (median age ∼55 years, 55% male, Acute Physiology and Chronic Health Evaluation II ∼24, >90% mechanically ventilated) were randomized (60 intervention; 55 control). Enrollment was stopped early due to slow recruitment, with no evidence of safety concerns. The mean duration of cycling was 40 ± 7 min/d (control: 0 min/d), with total protein intake of 1.9 ± 0.6 g/kg/d (control: 0.9 ± 0.6). The median (interquartile range) 6MWD was similar between intervention and control: 108 (15-242) and 95 (0-196) m (P = .51) (median difference, 10; 95% CI, -75 to 84). Secondary outcomes were also similar between groups. CONCLUSION: Among patients with ARF, a combined intervention of early in-bed cycling and amino acid supplementation appeared safe but did not improve 6MWD or secondary outcomes during hospitalization or 6-month follow-up. Clinicaltrials.gov (NCT03021902).