TY - JOUR
T1 - Azithromycin for early pseudomonas infection in cystic fibrosis the OPTIMIZE randomized trial
AU - Mayer-Hamblett, Nicole
AU - Retsch-Bogart, George
AU - Kloster, Margaret
AU - Accurso, Frank
AU - Rosenfeld, Margaret
AU - Albers, Gary
AU - Black, Philip
AU - Brown, Perry
AU - Cairns, Anne Marie
AU - Davis, Stephanie D.
AU - Graff, Gavin R.
AU - Kerby, Gwendolyn S.
AU - Orenstein, David
AU - Buckingham, Rachael
AU - Ramsey, Bonnie W.
N1 - Funding Information:
Supported by NIH grants U01HL114623 and U01HL114589. Additional support was provided through NIH Clinical and Translational Science Awards UL1TR002319, UL1TR001108, UL1TR1425, and UL1TR001082.
Funding Information:
Acknowledgment: The authors thank the children with CF and their families who participated in this study, and whose dedication to research made this trial possible. They also thank the NHLBI (including Lora Reineck, John Sheridan, and Lisa Viviano) for programmatic support, and the study Data Safety Monitoring Board (including Felix Ratjen, David Reboussin, Ron Rubenstein, Brian O’Sullivan, Pranita Tamma, Mary Jayne Kennedy, Renee Moore, and Dong-Yun Kim). They thank Pfizer for providing the azithromycin and placebo formulations for the 18-month duration of the study, Novartis for providing the tobramycin solution for inhalation (TOBI) for the initial Pa eradication protocol, and PARI for providing compressors and nebulizers for TOBI administration. Finally, the authors thank the Cystic Fibrosis Foundation for supporting this clinical trial through the CF Therapeutics Development Network.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Rationale: New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach that complements traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation and inflammation may ultimately prolong the time to Pa recurrence. Objectives: To test the hypothesis that the addition of azithromycin to TIS in children with cystic fibrosis and early Pa decreases the risk of pulmonary exacerbation and prolongs the time to Pa recurrence. Methods: The OPTIMIZE (Optimizing Treatment for Early Pseudomonas aeruginosa Infection in Cystic Fibrosis) trial was a multicenter, double-blind, randomized, placebo-controlled, 18-month trial in children with CF, 6 months to 18 years of age, with early Pa. Azithromycin or placebo was given 33weekly with standardized TIS. Measurements and Main Results: The primary endpoint was the time to pulmonary exacerbation requiring antibiotics and the secondary endpoint was the time to Pa recurrence, in addition to other clinical and safety outcomes. A total of 221 participants (111 placebo, 110 azithromycin) out of a planned 274 were enrolled. Enrollment was stopped early by the NHLBI because the trial had reached the prespecified interim boundary for efficacy. The risk of pulmonary exacerbation was reduced by 44% in the azithromycin group as compared with the placebo group (hazard ratio, 0.56; 95% confidence interval, 0.37-0.83; P = 0.004). Weight increased by 1.27 kg in the azithromycin group compared with the placebo group (95% confidence interval, 0.01-2.52; P = 0.046). No significant differences were seen in microbiological or other clinical or safety endpoints. Conclusions: Azithromycin was associated with a significant reduction in the risk of pulmonary exacerbation and a sustained improvement in weight, but had no impact on microbiological outcomes in children with early Pa. Clinical trial registered with clinicaltrials.gov (NCT02054156).
AB - Rationale: New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach that complements traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation and inflammation may ultimately prolong the time to Pa recurrence. Objectives: To test the hypothesis that the addition of azithromycin to TIS in children with cystic fibrosis and early Pa decreases the risk of pulmonary exacerbation and prolongs the time to Pa recurrence. Methods: The OPTIMIZE (Optimizing Treatment for Early Pseudomonas aeruginosa Infection in Cystic Fibrosis) trial was a multicenter, double-blind, randomized, placebo-controlled, 18-month trial in children with CF, 6 months to 18 years of age, with early Pa. Azithromycin or placebo was given 33weekly with standardized TIS. Measurements and Main Results: The primary endpoint was the time to pulmonary exacerbation requiring antibiotics and the secondary endpoint was the time to Pa recurrence, in addition to other clinical and safety outcomes. A total of 221 participants (111 placebo, 110 azithromycin) out of a planned 274 were enrolled. Enrollment was stopped early by the NHLBI because the trial had reached the prespecified interim boundary for efficacy. The risk of pulmonary exacerbation was reduced by 44% in the azithromycin group as compared with the placebo group (hazard ratio, 0.56; 95% confidence interval, 0.37-0.83; P = 0.004). Weight increased by 1.27 kg in the azithromycin group compared with the placebo group (95% confidence interval, 0.01-2.52; P = 0.046). No significant differences were seen in microbiological or other clinical or safety endpoints. Conclusions: Azithromycin was associated with a significant reduction in the risk of pulmonary exacerbation and a sustained improvement in weight, but had no impact on microbiological outcomes in children with early Pa. Clinical trial registered with clinicaltrials.gov (NCT02054156).
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U2 - 10.1164/rccm.201802-0215OC
DO - 10.1164/rccm.201802-0215OC
M3 - Article
C2 - 29890086
AN - SCOPUS:85054384051
VL - 198
SP - 1177
EP - 1187
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 9
ER -