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A Randomized Controlled Trial

Lisa Saiman, MD, MPH; Bruce C. Marshall, MD; Nicole Mayer-Hamblett, PhD; Jane L. Burns, MD; Alexandra L. Quittner, PhD; Debra A. Cibene, CCRA; Sarah Coquillette; Ann Yunker Fieberg, MS; Frank J. Accurso, MD; Preston W. Campbell III, MD; for the Macrolide Study Group

JAMA. 2003;290:1749-1756.

Context  Treatment strategies for cystic fibrosis (CF) lung disease include antibiotics, mucolytics, and anti-inflammatory therapies. Increasing evidence suggests that macrolide antibiotics might be beneficial in patients with CF.

Objective  To determine if an association between azithromycin use and pulmonary function exists in patients with CF.

Design and Setting  A multicenter, randomized, double-blind, placebo-controlled trial conducted from December 15, 2000, to May 2, 2002, at 23 CF care centers in the United States.

Participants  Of the 251 screened participants with a diagnosis of CF, 185 (74%) were randomized. Eligibility criteria included age 6 years or older, infection with Pseudomonas aeruginosa for 1 or more years, and a forced expiratory volume in 1 second (FEV₁) of 30% or more. Participants were stratified by FEV₁ (60% predicted vs <60% predicted), weight of less than 40 kg vs 40 kg or more, and CF center.

Intervention  The active group (n = 87) received 250 mg (weight <40 kg) or 500 mg (weight 40 kg) of oral azithromycin 3 days a week for 168 days; placebo group (n = 98) received identically packaged tablets.

Main Outcome Measures  Change in FEV₁ from day 0 to completion of therapy at day 168 and determination of safety. Secondary outcomes included pulmonary exacerbations and weight gain.

Results  The azithromycin group had a mean 0.097-L (SD, 0.26) increase in FEV₁ at day 168 compared with 0.003 L (SD, 0.23) in the placebo group (mean difference, 0.094 L; 95% confidence interval [CI], 0.023-0.165; P = .009). Nausea occurred in 17% more participatns in the azithromycin group (P = .01), diarrhea in 15% more (P = .009), and wheezing in 13% more (P = .007). Participants in the azithromycin group had less risk of experiencing an exacerbation than participants in the placebo group (hazard ratio, 0.65; 95% CI, 0.44-0.95; P = .03) and weighed at the end of the study an average 0.7 kg more than participants receiving placebo (95% CI, 0.1-1.4 kg; P = .02).

Conclusion  Azithromycin treatment was associated with improvement in clinically relevant end points and should be considered for patients with CF who are 6 years or older and chronically infected with P aeruginosa.

Author Affiliations: Department of Pediatrics, Columbia University, New York, NY (Dr Saiman); Department of Internal Medicine, University of Utah, Salt Lake City (Dr Marshall); Departments of Biostatistics (Dr Mayer-Hamblett) and Pediatrics (Drs Mayer-Hamblett and Burns), University of Washington, Seattle; Cystic Fibrosis Therapeutics Development Network Coordinating Center, Seattle, Wash (Dr Mayer-Hamblett and Mss Cibene, Coquillette, and Fieberg); Cystic Fibrosis Therapeutic Development Network Resource Center for CF Microbiology, Seattle, Wash (Dr Burns); Department of Clinical and Health Psychology, Department of Pediatrics, University of Florida, Gainesville (Dr Quittner); Department of Pediatrics, University of Colorado, and Cystic Fibrosis Therapeutic Development Network Resource Center for Inflammatory Markers (Dr Accurso), Denver, Colo; and Cystic Fibrosis Foundation, Bethesda, Md (Drs Marshall and Campbell).

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