Effectiveness of nebulised 7% saline versus oral carbocisteine in patients with COPD and self-reported difficulty in expectoration: a randomised controlled trial (MUCACT)

Background This was an open, pragmatic, UK, multicentre and parallel randomised controlled trial in participants with COPD and self-reported difficulty in expectorating. Methods Participants were randomised to receive either nebulised 7% saline plus the active cycle breathing technique (ACBT) twice daily or carbocisteine plus ACBT twice daily for 12 months. The primary objective was to assess whether the 7% saline was superior to the carbocisteine when comparing the change in COPD Assessment Test (CAT) score over 12 months. Results Due to difficulty in recruitment post-COVID-19, the funding was stopped after 206 of the planned 860 participants completed the study. 102 participants were in the 7% saline arm and 104 in the carbocisteine arm. Comparing arms, there was no improvement of CAT scores at 12 months (mean difference 1.41 (95% CI −1.83–4.65); p=0.373). There were fewer exacerbations in the 7% saline arm (p=0.017) with a 37% reduction in risk of exacerbations (hazard ratio 0.628 (95% CI 0.399–0.988), p=0.044). There was no significant difference in quality-of-life questionnaires apart from worsening cough in the 7% saline arm and no significant difference in lung function tests or serious adverse events at 12 m. Conclusions Comparing arms, there was no improvement of CAT scores at 12 months, but the study was underpowered for this end-point. There was, however, significantly fewer exacerbations in the 7% saline arm, with a 37% reduction in risk of exacerbations. 7% saline may be a useful adjunct to standard chest clearance in patients with COPD that report difficulty in self-expectoration, in reducing exacerbations, but further studies are needed.