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

Autor: Gilchrist FJ; Paediatric Respiratory Services, Staffordshire Children's Hospital at Royal Stoke, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK; Institute of Applied Clinical Science, Keele University, Stoke-on-Trent, UK. Electronic address: francis.gilchrist@uhnm.nhs.uk., Bui S; Bordeaux University Hospital, Hôpital Pellegrin-Enfants, Paediatric Cystic Fibrosis Reference Center (CRCM), Centre d'Investigation Clinique (CIC 1401), Bordeaux, France. Electronic address: stephanie.bui@chu-bordeaux.fr., Gartner S; Paediatric Pulmonology and Cystic Fibrosis Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Electronic address: silvia.gartner@vallhebron.cat., McColley SA; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Division of Pulmonary and Sleep Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA. Electronic address: smccolle@luriechildrens.org., Tiddens H; Department of Pediatric Pulmonology and Allergology, Erasmus MC Sophia Children's Hospital, Rotterdam, Netherlands. Electronic address: h.tiddens@erasmusmc.nl., Ruiz G; Department of Paediatric Respiratory Medicine, King's College Hospital NHS Foundation Trust, London, UK. Electronic address: gary.ruiz@nhs.net., Stehling F; Pediatric Pulmonology and Sleep Medicine, Cystic Fibrosis Center, Children's Hospital, University Duisburg-Essen, Essen, Germany. Electronic address: florian.stehling@uk-essen.de., Alani M; Gilead Sciences Inc., Foster City, CA, USA; Division of Rheumatology, University of Washington, Seattle, WA, USA. Electronic address: muhsen.alani@gilead.com., Gurtovaya O; Gilead Sciences Inc., Foster City, CA, USA. Electronic address: Oksana.Gurtovaya@gilead.com., Bresnik M; Gilead Sciences Inc., Foster City, CA, USA. Electronic address: mbresnikmd@gmail.com., Watkins TR; Gilead Sciences Inc., Foster City, CA, USA. Electronic address: Tim.Watkins@gilead.com., Frankovic B; Gilead Sciences Inc., Foster City, CA, USA. Electronic address: Biliana.Frankovic@gilead.com., Skov M; CF Centre Copenhagen, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Electronic address: marianne.skov@regionh.dk.
Jazyk: angličtina
Zdroj: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society [J Cyst Fibros] 2024 Jan; Vol. 23 (1), pp. 80-86. Date of Electronic Publication: 2023 Jul 15.
DOI: 10.1016/j.jcf.2023.06.008
Abstrakt: 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: NCT03219164.
Competing Interests: Declaration of Competing Interest SAM has received advisory fees from Vertex Pharmaceuticals, Inc. FS has received speaking and consulting fees from Gilead Sciences, Inc. and Vertex Pharmaceuticals, Inc. MA, OG, TRW and BF are employees and shareholders of Gilead Sciences, Inc. MB is a former employee and shareholder of Gilead Sciences, Inc. MS has received speaking fees from Vertex Pharmaceuticals, Inc. All other authors declare that they have nothing to disclose.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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