Early anti-pseudomonal acquisition in young patients with cystic fibrosis: Rationale and design of the EPIC clinical trial and observational study

TypeofStudy:An open study comparing the clinical and microbiological efficacy and safety of culture-based therapy versus cycled therapy with Tobi, initiated at the time of early Pseudomonas aeruginosa (Pa) infection of the respiratory tract in young cystic fibrosis (CF) patients. The Early Pseudomonas Infection Control (EPIC) program consisted of 2 studies, a randomized, multicenter trial (EPIC-CT) in CF patients ages 1-12 years at first isolation of Pa from a respiratory culture, and a longitudinal, observational (EPIC-OBS) cohort study enrolling Pa-negative patients. NCT identifier: NCT00676169, NCT00097773.

Indications:For the prevention and treatment of Pseudomonas aeruginosa infection in 300 patients. Coexisting disease: cystic fibrosis.

Patients:300 male and female outpatients, age range 1-12 years. 150 in the clinical trial and 150 in the cohort study.

DosageDuration:300 mg bid (=600 mg daily) inhalationally for 28 days in monotherapy followed by 56 days off therapy, for 6 quarterly cycles (cycled therapy) or to be repeated when quarterly respiratory cultures were found positive for Pa (culture-based therapy).

FreeText:Primary endpoints: the time to pulmonary exacerbation requiring intravenous antibiotics or hospitalization for respiratory symptoms, and the proportion of patients with new Pa-positive respiratory cultures during the study. Secondary endpoints: time to pulmonary exacerbation not requiring intravenous antibiotic usage or hospitalization; frequencies of pulmonary exacerbations, hospitalizations; and use of concomitant oral, inhaled, and intravenous antibiotics; anthropometric measures (linear growth, weight gain); pulmonary function tests; and total hospitalization days; the microbiologic profile of Pa isolates from respiratory cultures as indicated by changes in antibiotic susceptibility patterns, colony morphology, and the presence of mucoid isolates. The emergence of intrinsically aminoglycoside- and ciprofloxacin-resistant nonpseudomonal organisms is also evaluated. Other endpoints: risk factors (Pa serology and Pa phenotype) and outcomes associated with early acquisition of Pa. Safety measures: emergence of organ toxicities detected by serial evaluation of articular/skeletal symptoms, renal function, hearing acuity, liver function, hematological profile, and adverse events. Concomitant drugs: oral ciprofloxacin 15-20 mg/kg twice daily (30-40 mg/kg daily) or oral placebo for 14 days; other oral, inhaled, and intravenous antibiotics.

Results:Results will be published later.

AdverseEffects:No adverse events were mentioned.

AuthorsConclusions:In conclusion, this study will provide valuable clinical and microbiologic efficacy and safety data regarding the optimal use of antipseudomonal therapy in young children with CF, and the long-term follow-up of this unique cohort of children will supply important data on the effect of Pa infection on subsequent health status, and the linked serum and DNA banks will contribute valuable information on surrogate markers and genetic modifiers of early CF lung disease.