RATIONALE: Cystic fibrosis (CF) lung disease starts in early infancy suggesting that preventive treatment may be most beneficial. Lung clearance index (LCI) and chest magnetic resonance imaging (MRI) have emerged as promising endpoints of early CF lung disease, however, randomized controlled trials testing the safety and efficacy of preventive therapies in infants with CF are lacking. OBJECTIVES: To determine feasibility, safety and efficacy of preventive inhalation with hypertonic saline (HS) compared to isotonic saline (IS) in infants with CF including LCI and MRI as outcome measures. METHODS AND MAIN RESULTS: In this randomized, double-blind, controlled trial 42 infants with CF less than 4 months of age were randomized across 5 sites to twice daily inhalation of 6% HS (n=21) or 0.9% IS (n=21) for 52 weeks. Inhalation of HS and IS was generally well tolerated by CF infants and the number of adverse events did not differ between groups (P=0.49). The change in LCI from baseline to week 52 was larger in CF infants treated with HS (-0.6) compared to IS (-0.1, P<0.05). In addition, weight gain was improved in CF infants treated with HS (P<0.05), whereas pulmonary exacerbations and chest MRI scores did not differ in the HS vs. IS group. CONCLUSIONS: Preventive inhalation with HS initiated in the first months of life was safe and well tolerated, and resulted in improvements in LCI and weight gain in infants with CF. Our results support feasibility of LCI as endpoint in randomized controlled trials in infants with CF. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01619657.
- Stahl, M.
- Wielputz, M. O.
- Ricklefs, I.
- Dopfer, C.
- Barth, S.
- Schlegtendal, A.
- Graeber, S. Y.
- Sommerburg, O.
- Diekmann, G.
- Husing, J.
- Koerner-Rettberg, C.
- Nahrlich, L.
- Dittrich, A. M.
- Kopp, M. V.
- Mall, M. A.
Keywords
- Cystic fibrosis
- lung clearance index
- lung disease
- magnetic resonance imaging
- preventive therapy
