Multimodal nutritional rehabilitation improves clinical outcomes of malnourished patients with chronic respiratory failure: a randomised controlled trial

Multicentre randomized controlled trial conducted across eight respiratory units. In the multimodal rehabilitation arm, 60 malnourished adults with chronic respiratory failure on long-term oxygen therapy and/or home mechanical ventilation were randomized; participants were mostly male ex-smokers with COPD, with mean age 66 (10) years.

The active regimen was a 3-month home-based multimodal rehabilitation program that included oral nutritional supplements and oral testosterone undecanoate, alongside exercise training and health education. Oral testosterone undecanoate was given at 80 mg twice daily in men and 40 mg twice daily in women; the oral nutritional supplement was 3 x 120 mL/day of Respifor, providing 188 kcal per serving, and both supplement components were stopped on day 90.

The multimodal program improved body composition, muscle function, exercise capacity, and some patient-reported outcomes, but did not significantly improve the primary 6-minute walk distance outcome. Compared with control, BMI increased by 0.56 kg/m2 (95% CI 0.18 to 0.95, p=0.004), FFMI by 0.60 kg/m2 (95% CI 0.15 to 1.05, p=0.01), haemoglobin by 9.1 g/l (95% CI 2.5 to 15.7, p=0.008), peak workload by 7.2 W (95% CI 3.7 to 10.6, p<0.001), quadriceps isometric force by 28.3 N (95% CI 7.2 to 49.3, p=0.009), and endurance time by 5.9 min (95% CI 3.1 to 8.8, p<0.001). In women, CRQ improved by 16.5 units (95% CI 5.3 to 27.7, p=0.006), and per-protocol survival was better (HR 0.287, 95% CI 0.08 to 0.95, p=0.042).

The intervention was a bundled multimodal program, so the specific contribution of the oral nutritional supplement cannot be isolated. The trial was short duration (3 months), the primary endpoint was not significant, and survival was reported in a per-protocol analysis. The sample was relatively small and predominantly male patients with COPD, limiting generalizability, and the intervention arm had a higher reported exacerbation rate than control (0.36 vs 0.14, p=0.045).