Abstract
Background
Pulmonary rehabilitation (PR) is the cornerstone of non-pharmacological treatment for chronic obstructive pulmonary disease (COPD), yet fatigue often persists despite rehabilitation. We conducted a multicentre, randomised, double-blind, placebo-controlled trial to evaluate whether oral L-arginine plus liposomal vitamin C improves fatigue in patients with advanced COPD and chronic respiratory failure (CRF) undergoing PR.
Methods
Consecutive patients with stable COPD and CRF receiving long-term oxygen therapy were randomised to L-arginine/liposomal vitamin C or placebo during a standardised 28-day PR programme. Fatigue was assessed using the Fatigue Severity Scale (FSS). The primary analysis used a longitudinal linear mixed-effects model including repeated FSS measurements, treatment group, time, treatment-by-time interaction and prespecified covariates. Secondary outcomes included 6 min walk distance, sit-to-stand test, handgrip strength, COPD Assessment Test and modified Medical Research Council dyspnoea score.
Results
98 participants were randomised. A significant difference was found in FSS changes between groups (mean difference −0.90; 95% CI −1.50 to −0.29; p=0.004), confirmed by the adjusted treatment-by-time interaction analysis (adjusted between-group difference −0.72; 95% CI −1.25 to −0.20; p=0.009). The point estimate exceeded the prespecified minimal clinically important difference (0.6 points). A higher proportion of participants achieved an FSS score
Conclusions
In patients with COPD and CRF undergoing PR, adjunctive oral L-arginine plus liposomal vitamin C was associated with a greater reduction in perceived fatigue, without significant improvements in functional or patient-reported secondary outcomes.
Trial registration number
NCT06439875
.