Azithromycin for Early Pseudomonas Infection in Cystic Fibrosis: The Optimize Randomized Trial.
Abstract
RATIONALE:
New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach complementing traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation (PEx) and inflammation may ultimately prolong time to Pa recurrence.
OBJECTIVES:
To test the hypothesis that the addition of azithromycin to TIS in children with CF and early Pa decreases the risk of PEx and prolongs time to Pa recurrence.
METHODS:
The OPTIMIZE trial was a multicenter, double-blind, randomized, placebo-controlled, 18-month trial in children with CF ages 6 months-18 years with early Pa. Azithromycin or placebo was given 3x weekly with standardized TIS.
MEASUREMENTS:
The primary endpoint was time to PEx requiring antibiotics and secondary endpoint time to Pa recurrence, in addition to other clinical and safety outcomes.
MAIN RESULTS:
221 participants (111 placebo, 110 azithromycin) out of a planned 274 were enrolled. Enrollment was stopped early by the National Heart, Lung, and Blood Institute (NHLBI) because the trial had reached the pre-specified interim boundary for efficacy. The risk of PEx was reduced by 44% in the azithromycin group as compared to placebo (hazard ratio [HR]: 0.56, 95% CI:0.37,0.83, p=0.004). Weight increased by 1.27 kg in the azithromycin group compared to placebo (95% CI:0.01,2.52, p=0.046). No significant differences were seen in microbiologic, clinical, or safety endpoints.
CONCLUSIONS:
Azithromycin was associated with a significant reduction in risk of PEx and sustained improvement in weight but had no impact on microbiologic outcomes in children with early Pa. Clinical trial registered with ClinicalTrials.gov (NCT02054156).
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