A phase II study on safety and efficacy of high-dose N-acetylcysteine in patients with cystic fibrosis.

OBJECTIVE: We conducted a single-centre, randomised, double-blinded, placebo-controlled phase II clinical study to test safety and efficacy of a 12-week therapy with low-dose (700 mg/daily) or high-dose (2800 mg/daily) of NAC. METHODS: Twenty-one patients (DeltaF508 homo/heterozygous, FEV1>40% pred.) were included in the study. After a 3-weeks placebo run-in phase, 11 patients received low-dose NAC, and 10 patients received high-dose NAC. Outcomes included safety and clinical parameters, inflammatory (total leukocyte numbers, cell differentials, TNF-alpha, IL-8) measures in induced sputum, and concentrations of extracellular glutathione in induced sputum and blood. RESULTS: High-dose NAC was a well-tolerated and safe medication. High-dose NAC did not alter clinical or inflammatory parameters. However, extracellular glutathione in induced sputum tended to increase on high-dose NAC. CONCLUSIONS: High-dose NAC is a well-tolerated and safe medication for a prolonged therapy of patients with CF with a potential to increase extracellular glutathione in CF airways.