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.
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
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.
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.
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).
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.