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

Aztreonam Cystic fibrosis, Eradication Paediatric Pseudomonas aeruginosa Respiratory infections

Journal

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
ISSN: 1873-5010
Titre abrégé: J Cyst Fibros
Pays: Netherlands
ID NLM: 101128966

Informations de publication

Date de publication:
Jan 2024
Historique:
received: 06 03 2023
revised: 06 06 2023
accepted: 21 06 2023
pubmed: 17 7 2023
medline: 17 7 2023
entrez: 16 7 2023
Statut: ppublish

Résumé

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. 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). 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. 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. GOV: NCT03219164.

Sections du résumé

BACKGROUND 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 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 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 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 RESULTS
GOV: NCT03219164.

Identifiants

DOI: 10.1016/j.jcf.2023.06.008 PMID: 37455237
pubmed: 37455237
pii: S1569-1993(23)00821-4
doi: 10.1016/j.jcf.2023.06.008
pii:
doi:

Banques de données

ClinicalTrials.gov
['NCT03219164']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

80-86

Informations de copyright

Copyright © 2023. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

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.

Auteurs

Francis J 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.

Stephanie 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.

Silvia Gartner (S)

Paediatric Pulmonology and Cystic Fibrosis Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Electronic address: silvia.gartner@vallhebron.cat.

Susanna A 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.

Harm Tiddens (H)

Department of Pediatric Pulmonology and Allergology, Erasmus MC Sophia Children's Hospital, Rotterdam, Netherlands. Electronic address: h.tiddens@erasmusmc.nl.

Gary Ruiz (G)

Department of Paediatric Respiratory Medicine, King's College Hospital NHS Foundation Trust, London, UK. Electronic address: gary.ruiz@nhs.net.

Florian 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.

Muhsen Alani (M)

Gilead Sciences Inc., Foster City, CA, USA; Division of Rheumatology, University of Washington, Seattle, WA, USA. Electronic address: muhsen.alani@gilead.com.

Oksana Gurtovaya (O)

Gilead Sciences Inc., Foster City, CA, USA. Electronic address: Oksana.Gurtovaya@gilead.com.

Mark Bresnik (M)

Gilead Sciences Inc., Foster City, CA, USA. Electronic address: mbresnikmd@gmail.com.

Timothy R Watkins (TR)

Gilead Sciences Inc., Foster City, CA, USA. Electronic address: Tim.Watkins@gilead.com.

Biliana Frankovic (B)

Gilead Sciences Inc., Foster City, CA, USA. Electronic address: Biliana.Frankovic@gilead.com.

Marianne 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.

Classifications MeSH