Cystic fibrosis (CF) remains one of the most common lethal genetic diseases in Europe and North America. Despite a substantial increase in life expectancy over the past decades, many CF patients still die during young adulthood due to chronic progressive CF lung disease that is caused by defective fluid transport by airway epithelia causing dehydration of airway surfaces, which in turn leads to impaired mucociliary clearance, chronic airway mucus obstruction, inflammation and infection. Recent evidence from studies in a mouse model of CF lung disease suggest that preventive improvement of airway surface hydration may be an effective treatment of early and reversible mucus obstruction and inflammation, and thus delay or ameliorate progressive damage in lungs of CF patients. Hypertonic saline (HS) is an osmotic agent that improves airway surface hydration, and inhalation of 6% HS is already an established, safe, and effective maintenance therapy that improves mucociliary clearance and lung function, and reduces pulmonary exacerbations in older children (> 6 years) and adults with chronic CF lung disease and fixed lung damage. However, the effect of HS as a preventive therapy has not been studied, and no other therapies are available for preventive improvement of airway dehydration and mucociliary dysfunction in CF.~This investigator initiated clinical trial is a monocentric, randomized, double-blind, controlled pilot study on safety and efficacy of a preventive and early inhalation with HS in newborns and infants with CF who are diagnosed in the newborn period either by CF newborn screening (CF-NBS) or for another reason (e.g. meconium ileus) and are younger than 4 months of age at the time of enrolment. Participating patients will be randomized to 6% HS or 0.9% isotonic saline (IS) as active comparator. In both groups, patients will inhale their study solution twice daily over 52 weeks. At the beginning, during and at the end of the study, different measurements will be undertaken to determine effects of HS on safety, radiologic and/or functional alterations of the lung, number of exacerbations, time to first detection of a CF pathogen, and health-related quality of life. We expect that the results of this study will provide first evidence on the safety and efficacy of a preventive therapy that improves airway surface hydration and targets a CF basic defect and may thus delay and/or ameliorate chronic damage of the lungs of patients with CF.
The purpose of this study is to assess whether 6% hypertonic saline (HS) is a safe and effective preventive therapy in newborns and infants with cystic fibrosis (CF).