ALPINE2: Efficacy and safety of 14-day vs 28-day inhaled aztreonam for Pa eradication in children with cystic fibrosis

Francis J. Gilchrist*, Stephanie Bui, ALPINE2 study investigators, Silvia Gartner, Susanna A. McColley, Harm Tiddens, Gary Ruiz, Florian Stehling, Muhsen Alani, Oksana Gurtovaya, Mark Bresnik, Timothy R. Watkins, Biliana Frankovic, Marianne Skov

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background: Antibiotic eradication therapies recommended for newly isolated Pseudomonas aeruginosa (Pa) in people with cystic fibrosis (pwCF) can be burdensome. ALPINE2 compared the efficacy and safety of a shortened 14-day course of aztreonam for inhalation solution (AZLI) with 28-day AZLI in paediatric pwCF. Methods: ALPINE2 (a double-blind, phase 3b study) included children aged 3 months to <18 years with CF and new-onset Pa infection. Participants were randomized to receive 75 mg AZLI three times daily for either 28 or 14 days followed by 14 days' matched placebo. The primary endpoint was rate of primary Pa eradication (no Pa detected during the 4 weeks post AZLI treatment). Non-inferiority was achieved if the lower 95% CI bound of the treatment difference between the two arms was above −20%. Secondary endpoints included assessments of Pa recurrence during 108 weeks of follow-up after primary eradication. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In total, 149 participants were randomized (14-day AZLI, n = 74; 28-day AZLI, n = 75) and 142 (95.3%) completed treatment. Median age: 6.0 years (range: 0.3–17.0). Baseline characteristics were similar between treatment arms. Primary Pa eradication rates: 14-day AZLI, 55.9%; 28-day AZLI, 63.4%; treatment difference (CI), −8.0% (−24.6, 8.6%). Pa recurrence rates at follow-up end: 14-day AZLI, 54.1% (n = 20/37); 28-day AZLI, 41.9% (n = 18/43). TEAEs were similar between treatment arms. No new safety signals were observed. Conclusions: Non-inferiority of 14-day AZLI versus 28-day AZLI was not demonstrated. Both courses were well tolerated, further supporting AZLI short-term safety in paediatric and adolescent pwCF. ClinicalTrials.gov:

Original languageEnglish
Pages (from-to)80-86
Number of pages7
JournalJournal of Cystic Fibrosis
Volume23
Issue number1
Early online date14 Jul 2023
DOIs
Publication statusPublished - Jan 2024

Bibliographical note

Funding source
This ALPINE2 study was sponsored by Gilead Sciences, Inc. Gilead Sciences, Inc. were responsible for study design, data collection and analysis, writing the study report and making the decision to submit the article for publication. Medical writing support for the preparation of this manuscript was provided by Elvi Nimali, MBiochem, of PharmaGenesis London,
London, UK, and funded by Gilead Sciences, Inc.

Publisher Copyright: © 2023

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