Azithromycin for early pseudomonas infection in cystic fibrosis the OPTIMIZE randomized trial

Nicole Mayer-Hamblett, George Retsch-Bogart, Margaret Kloster, Frank Accurso, Margaret Rosenfeld, Gary Albers, Philip Black, Perry Brown, Anne Marie Cairns, Stephanie Davis, Gavin R. Graff, Gwendolyn S. Kerby, David Orenstein, Rachael Buckingham, Bonnie W. Ramsey

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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).

Original languageEnglish (US)
Pages (from-to)1177-1187
Number of pages11
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume198
Issue number9
DOIs
StatePublished - Nov 1 2018

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Pseudomonas Infections
Azithromycin
Cystic Fibrosis
Pseudomonas aeruginosa
Placebos
Tobramycin
Inhalation
Lung
Recurrence
Confidence Intervals
Anti-Bacterial Agents
National Heart, Lung, and Blood Institute (U.S.)
Safety
Weights and Measures
Risk Reduction Behavior
Pneumonia
Therapeutics
Clinical Trials

Keywords

  • clinical trial
  • eradication
  • Pseudomonas aeruginosa
  • pulmonary exacerbation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Mayer-Hamblett, N., Retsch-Bogart, G., Kloster, M., Accurso, F., Rosenfeld, M., Albers, G., ... Ramsey, B. W. (2018). Azithromycin for early pseudomonas infection in cystic fibrosis the OPTIMIZE randomized trial. American Journal of Respiratory and Critical Care Medicine, 198(9), 1177-1187. https://doi.org/10.1164/rccm.201802-0215OC

Azithromycin for early pseudomonas infection in cystic fibrosis the OPTIMIZE randomized trial. / Mayer-Hamblett, Nicole; Retsch-Bogart, George; Kloster, Margaret; Accurso, Frank; Rosenfeld, Margaret; Albers, Gary; Black, Philip; Brown, Perry; Cairns, Anne Marie; Davis, Stephanie; Graff, Gavin R.; Kerby, Gwendolyn S.; Orenstein, David; Buckingham, Rachael; Ramsey, Bonnie W.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 198, No. 9, 01.11.2018, p. 1177-1187.

Research output: Contribution to journalArticle

Mayer-Hamblett, N, Retsch-Bogart, G, Kloster, M, Accurso, F, Rosenfeld, M, Albers, G, Black, P, Brown, P, Cairns, AM, Davis, S, Graff, GR, Kerby, GS, Orenstein, D, Buckingham, R & Ramsey, BW 2018, 'Azithromycin for early pseudomonas infection in cystic fibrosis the OPTIMIZE randomized trial', American Journal of Respiratory and Critical Care Medicine, vol. 198, no. 9, pp. 1177-1187. https://doi.org/10.1164/rccm.201802-0215OC
Mayer-Hamblett, Nicole ; Retsch-Bogart, George ; Kloster, Margaret ; Accurso, Frank ; Rosenfeld, Margaret ; Albers, Gary ; Black, Philip ; Brown, Perry ; Cairns, Anne Marie ; Davis, Stephanie ; Graff, Gavin R. ; Kerby, Gwendolyn S. ; Orenstein, David ; Buckingham, Rachael ; Ramsey, Bonnie W. / Azithromycin for early pseudomonas infection in cystic fibrosis the OPTIMIZE randomized trial. In: American Journal of Respiratory and Critical Care Medicine. 2018 ; Vol. 198, No. 9. pp. 1177-1187.
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abstract = "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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AU - Rosenfeld, Margaret

AU - Albers, Gary

AU - Black, Philip

AU - Brown, Perry

AU - Cairns, Anne Marie

AU - Davis, Stephanie

AU - Graff, Gavin R.

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