Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIR-BX1 and AIR-BX2): Two randomised double-blind, placebo-controlled phase 3 trials

Alan F. Barker, Anne E. O'Donnell, Patrick Flume, Philip J. Thompson, Jonathan D. Ruzi, Javier De Gracia, Wim G. Boersma, Anthony De Soyza, Lixin Shao, Jenny Zhang, Laura Haas, Sandra A. Lewis, Sheila Leitzinger, A. Bruce Montgomery, Matthew T. McKevitt, David Gossage, Alexandra Quittner, Thomas G. O'Riordan

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Background: The clinical benefit of inhaled antibiotics in non-cystic fibrosis bronchiectasis has not been established in randomised controlled trials. We aimed to assess safety and efficacy of aztreonam for inhalation solution (AZLI) in patients with non-cystic fibrosis bronchiectasis and Gram-negative bacterial colonisation. Methods: AIR-BX1 and AIR-BX2 were two double-blind, multicentre, randomised, placebo-controlled phase 3 trials, which included patients aged 18 years or older who had bronchiectasis and history of positive sputum or bronchoscopic culture for target Gram-negative organisms. Patients were randomly assigned to receive either AZLI or placebo (1:1). Randomisation was done without stratification and the code was generated by a Gilead designee. In both studies, two 4-week courses of AZLI 75 mg or placebo (three-times daily; eFlow nebulizer) were each followed by a 4-week off-treatment period. Primary endpoint was change from baseline Quality of Life-Bronchiectasis Respiratory Symptoms scores (QOL-B-RSS) at 4 weeks. These trials are registered with ClinicalTrials.gov, numbers are NCT01313624 for AIR-BX1 and NCT01314716 for AIR-BX2. Findings: We recruited participants from 47 ambulatory clinics for AIR-BX1 and 65 ambulatory clinics for AIR-BX2; studies were done between April 25, 2011, and July 1, 2013. In AIR-BX1, of the 348 patients screened, 134 were randomly assigned to receive AZLI and 132 to receive placebo. In AIR-BX2, of the 404 patients screened, 136 were randomly assigned to receive AZLI and 138 to receive placebo. The difference between AZLI and placebo for adjusted mean change from baseline QOL-B-RSS was not significant at 4 weeks (0·8 [95% CI -3·1 to 4·7], p=0·68) in AIR-BX1, but was significant (4·6 [1·1 to 8·2], p=0·011) in AIR-BX2. The 4·6 point difference in QOL-B-RSS after 4 weeks in AIR-BX2 was not deemed clinically significant. In both studies, treatment-related adverse events were more common in the AZLI group than in the placebo group, as were discontinuations from adverse events. The most commonly reported treatment-emergent adverse events were dyspnea, cough, and increased sputum. Each was more common for AZLI-treated than for placebo-treated patients, but the incidences were more balanced in AIR-BX2. Interpretation: AZLI treatment did not provide significant clinical benefit in non-cystic fibrosis bronchiectasis, as measured by QOL-B-RSS, suggesting a continued need for placebo-controlled studies to establish the clinical benefit of inhaled antibiotics in patients with this disorder. Funding: Gilead Sciences.

Original languageEnglish
Pages (from-to)738-749
Number of pages12
JournalThe Lancet Respiratory Medicine
Volume2
Issue number9
DOIs
StatePublished - Jan 1 2014

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Aztreonam
Bronchiectasis
Inhalation
Fibrosis
Placebos
Quality of Life
Sputum
Anti-Bacterial Agents
Nebulizers and Vaporizers
Therapeutics
Random Allocation
Cough
Dyspnea
Randomized Controlled Trials
Safety

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIR-BX1 and AIR-BX2) : Two randomised double-blind, placebo-controlled phase 3 trials. / Barker, Alan F.; O'Donnell, Anne E.; Flume, Patrick; Thompson, Philip J.; Ruzi, Jonathan D.; De Gracia, Javier; Boersma, Wim G.; De Soyza, Anthony; Shao, Lixin; Zhang, Jenny; Haas, Laura; Lewis, Sandra A.; Leitzinger, Sheila; Montgomery, A. Bruce; McKevitt, Matthew T.; Gossage, David; Quittner, Alexandra; O'Riordan, Thomas G.

In: The Lancet Respiratory Medicine, Vol. 2, No. 9, 01.01.2014, p. 738-749.

Research output: Contribution to journalArticle

Barker, AF, O'Donnell, AE, Flume, P, Thompson, PJ, Ruzi, JD, De Gracia, J, Boersma, WG, De Soyza, A, Shao, L, Zhang, J, Haas, L, Lewis, SA, Leitzinger, S, Montgomery, AB, McKevitt, MT, Gossage, D, Quittner, A & O'Riordan, TG 2014, 'Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIR-BX1 and AIR-BX2): Two randomised double-blind, placebo-controlled phase 3 trials', The Lancet Respiratory Medicine, vol. 2, no. 9, pp. 738-749. https://doi.org/10.1016/S2213-2600(14)70165-1
Barker, Alan F. ; O'Donnell, Anne E. ; Flume, Patrick ; Thompson, Philip J. ; Ruzi, Jonathan D. ; De Gracia, Javier ; Boersma, Wim G. ; De Soyza, Anthony ; Shao, Lixin ; Zhang, Jenny ; Haas, Laura ; Lewis, Sandra A. ; Leitzinger, Sheila ; Montgomery, A. Bruce ; McKevitt, Matthew T. ; Gossage, David ; Quittner, Alexandra ; O'Riordan, Thomas G. / Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIR-BX1 and AIR-BX2) : Two randomised double-blind, placebo-controlled phase 3 trials. In: The Lancet Respiratory Medicine. 2014 ; Vol. 2, No. 9. pp. 738-749.
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abstract = "Background: The clinical benefit of inhaled antibiotics in non-cystic fibrosis bronchiectasis has not been established in randomised controlled trials. We aimed to assess safety and efficacy of aztreonam for inhalation solution (AZLI) in patients with non-cystic fibrosis bronchiectasis and Gram-negative bacterial colonisation. Methods: AIR-BX1 and AIR-BX2 were two double-blind, multicentre, randomised, placebo-controlled phase 3 trials, which included patients aged 18 years or older who had bronchiectasis and history of positive sputum or bronchoscopic culture for target Gram-negative organisms. Patients were randomly assigned to receive either AZLI or placebo (1:1). Randomisation was done without stratification and the code was generated by a Gilead designee. In both studies, two 4-week courses of AZLI 75 mg or placebo (three-times daily; eFlow nebulizer) were each followed by a 4-week off-treatment period. Primary endpoint was change from baseline Quality of Life-Bronchiectasis Respiratory Symptoms scores (QOL-B-RSS) at 4 weeks. These trials are registered with ClinicalTrials.gov, numbers are NCT01313624 for AIR-BX1 and NCT01314716 for AIR-BX2. Findings: We recruited participants from 47 ambulatory clinics for AIR-BX1 and 65 ambulatory clinics for AIR-BX2; studies were done between April 25, 2011, and July 1, 2013. In AIR-BX1, of the 348 patients screened, 134 were randomly assigned to receive AZLI and 132 to receive placebo. In AIR-BX2, of the 404 patients screened, 136 were randomly assigned to receive AZLI and 138 to receive placebo. The difference between AZLI and placebo for adjusted mean change from baseline QOL-B-RSS was not significant at 4 weeks (0·8 [95{\%} CI -3·1 to 4·7], p=0·68) in AIR-BX1, but was significant (4·6 [1·1 to 8·2], p=0·011) in AIR-BX2. The 4·6 point difference in QOL-B-RSS after 4 weeks in AIR-BX2 was not deemed clinically significant. In both studies, treatment-related adverse events were more common in the AZLI group than in the placebo group, as were discontinuations from adverse events. The most commonly reported treatment-emergent adverse events were dyspnea, cough, and increased sputum. Each was more common for AZLI-treated than for placebo-treated patients, but the incidences were more balanced in AIR-BX2. Interpretation: AZLI treatment did not provide significant clinical benefit in non-cystic fibrosis bronchiectasis, as measured by QOL-B-RSS, suggesting a continued need for placebo-controlled studies to establish the clinical benefit of inhaled antibiotics in patients with this disorder. Funding: Gilead Sciences.",
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TY - JOUR

T1 - Aztreonam for inhalation solution in patients with non-cystic fibrosis bronchiectasis (AIR-BX1 and AIR-BX2)

T2 - Two randomised double-blind, placebo-controlled phase 3 trials

AU - Barker, Alan F.

AU - O'Donnell, Anne E.

AU - Flume, Patrick

AU - Thompson, Philip J.

AU - Ruzi, Jonathan D.

AU - De Gracia, Javier

AU - Boersma, Wim G.

AU - De Soyza, Anthony

AU - Shao, Lixin

AU - Zhang, Jenny

AU - Haas, Laura

AU - Lewis, Sandra A.

AU - Leitzinger, Sheila

AU - Montgomery, A. Bruce

AU - McKevitt, Matthew T.

AU - Gossage, David

AU - Quittner, Alexandra

AU - O'Riordan, Thomas G.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background: The clinical benefit of inhaled antibiotics in non-cystic fibrosis bronchiectasis has not been established in randomised controlled trials. We aimed to assess safety and efficacy of aztreonam for inhalation solution (AZLI) in patients with non-cystic fibrosis bronchiectasis and Gram-negative bacterial colonisation. Methods: AIR-BX1 and AIR-BX2 were two double-blind, multicentre, randomised, placebo-controlled phase 3 trials, which included patients aged 18 years or older who had bronchiectasis and history of positive sputum or bronchoscopic culture for target Gram-negative organisms. Patients were randomly assigned to receive either AZLI or placebo (1:1). Randomisation was done without stratification and the code was generated by a Gilead designee. In both studies, two 4-week courses of AZLI 75 mg or placebo (three-times daily; eFlow nebulizer) were each followed by a 4-week off-treatment period. Primary endpoint was change from baseline Quality of Life-Bronchiectasis Respiratory Symptoms scores (QOL-B-RSS) at 4 weeks. These trials are registered with ClinicalTrials.gov, numbers are NCT01313624 for AIR-BX1 and NCT01314716 for AIR-BX2. Findings: We recruited participants from 47 ambulatory clinics for AIR-BX1 and 65 ambulatory clinics for AIR-BX2; studies were done between April 25, 2011, and July 1, 2013. In AIR-BX1, of the 348 patients screened, 134 were randomly assigned to receive AZLI and 132 to receive placebo. In AIR-BX2, of the 404 patients screened, 136 were randomly assigned to receive AZLI and 138 to receive placebo. The difference between AZLI and placebo for adjusted mean change from baseline QOL-B-RSS was not significant at 4 weeks (0·8 [95% CI -3·1 to 4·7], p=0·68) in AIR-BX1, but was significant (4·6 [1·1 to 8·2], p=0·011) in AIR-BX2. The 4·6 point difference in QOL-B-RSS after 4 weeks in AIR-BX2 was not deemed clinically significant. In both studies, treatment-related adverse events were more common in the AZLI group than in the placebo group, as were discontinuations from adverse events. The most commonly reported treatment-emergent adverse events were dyspnea, cough, and increased sputum. Each was more common for AZLI-treated than for placebo-treated patients, but the incidences were more balanced in AIR-BX2. Interpretation: AZLI treatment did not provide significant clinical benefit in non-cystic fibrosis bronchiectasis, as measured by QOL-B-RSS, suggesting a continued need for placebo-controlled studies to establish the clinical benefit of inhaled antibiotics in patients with this disorder. Funding: Gilead Sciences.

AB - Background: The clinical benefit of inhaled antibiotics in non-cystic fibrosis bronchiectasis has not been established in randomised controlled trials. We aimed to assess safety and efficacy of aztreonam for inhalation solution (AZLI) in patients with non-cystic fibrosis bronchiectasis and Gram-negative bacterial colonisation. Methods: AIR-BX1 and AIR-BX2 were two double-blind, multicentre, randomised, placebo-controlled phase 3 trials, which included patients aged 18 years or older who had bronchiectasis and history of positive sputum or bronchoscopic culture for target Gram-negative organisms. Patients were randomly assigned to receive either AZLI or placebo (1:1). Randomisation was done without stratification and the code was generated by a Gilead designee. In both studies, two 4-week courses of AZLI 75 mg or placebo (three-times daily; eFlow nebulizer) were each followed by a 4-week off-treatment period. Primary endpoint was change from baseline Quality of Life-Bronchiectasis Respiratory Symptoms scores (QOL-B-RSS) at 4 weeks. These trials are registered with ClinicalTrials.gov, numbers are NCT01313624 for AIR-BX1 and NCT01314716 for AIR-BX2. Findings: We recruited participants from 47 ambulatory clinics for AIR-BX1 and 65 ambulatory clinics for AIR-BX2; studies were done between April 25, 2011, and July 1, 2013. In AIR-BX1, of the 348 patients screened, 134 were randomly assigned to receive AZLI and 132 to receive placebo. In AIR-BX2, of the 404 patients screened, 136 were randomly assigned to receive AZLI and 138 to receive placebo. The difference between AZLI and placebo for adjusted mean change from baseline QOL-B-RSS was not significant at 4 weeks (0·8 [95% CI -3·1 to 4·7], p=0·68) in AIR-BX1, but was significant (4·6 [1·1 to 8·2], p=0·011) in AIR-BX2. The 4·6 point difference in QOL-B-RSS after 4 weeks in AIR-BX2 was not deemed clinically significant. In both studies, treatment-related adverse events were more common in the AZLI group than in the placebo group, as were discontinuations from adverse events. The most commonly reported treatment-emergent adverse events were dyspnea, cough, and increased sputum. Each was more common for AZLI-treated than for placebo-treated patients, but the incidences were more balanced in AIR-BX2. Interpretation: AZLI treatment did not provide significant clinical benefit in non-cystic fibrosis bronchiectasis, as measured by QOL-B-RSS, suggesting a continued need for placebo-controlled studies to establish the clinical benefit of inhaled antibiotics in patients with this disorder. Funding: Gilead Sciences.

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