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; Silvia Gartner; Susanna A McColley; Harm Tiddens; Gary Ruiz; Florian Stehling; Muhsen Alani; Oksana Gurtovaya; Mark Bresnik; Timothy R Watkins; Biliana Frankovic; Marianne Skov; ALPINE2 study investigators

doi:10.1016/j.jcf.2023.06.008

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

^*Corresponding author for this work

Department of Paediatrics and Adolescent Medicine

1 Citation (Scopus)

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: NCT03219164.

Original language	English
Journal	Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
Volume	23
Issue number	1
Pages (from-to)	80-86
Number of pages	7
ISSN	1569-1993
DOIs	https://doi.org/10.1016/j.jcf.2023.06.008
Publication status	Published - Jan 2024

Keywords

Aztreonam
Cystic fibrosis, Eradication
Paediatric
Pseudomonas aeruginosa
Respiratory infections
Humans
Administration, Inhalation
Treatment Outcome
Aztreonam/adverse effects
Adolescent
Pseudomonas Infections/diagnosis
Anti-Bacterial Agents/therapeutic use
Child
Cystic Fibrosis/diagnosis

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Gilchrist, F. J., Bui, S., Gartner, S., McColley, S. A., Tiddens, H., Ruiz, G., Stehling, F., Alani, M., Gurtovaya, O., Bresnik, M., Watkins, T. R., Frankovic, B., Skov, M., & ALPINE2 study investigators (2024). ALPINE2: Efficacy and safety of 14-day vs 28-day inhaled aztreonam for Pa eradication in children with cystic fibrosis. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 23(1), 80-86. https://doi.org/10.1016/j.jcf.2023.06.008

ALPINE2: Efficacy and safety of 14-day vs 28-day inhaled aztreonam for Pa eradication in children with cystic fibrosis. / Gilchrist, Francis J; Bui, Stephanie; Gartner, Silvia et al.
In: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, Vol. 23, No. 1, 01.2024, p. 80-86.

Research output: Contribution to journal › Journal article › Research › peer-review

Gilchrist, FJ, Bui, S, Gartner, S, McColley, SA, Tiddens, H, Ruiz, G, Stehling, F, Alani, M, Gurtovaya, O, Bresnik, M, Watkins, TR, Frankovic, B, Skov, M & ALPINE2 study investigators 2024, 'ALPINE2: Efficacy and safety of 14-day vs 28-day inhaled aztreonam for Pa eradication in children with cystic fibrosis', Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, vol. 23, no. 1, pp. 80-86. https://doi.org/10.1016/j.jcf.2023.06.008

@article{4c043269ba3e4034b8964b834b4e4e41,

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

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: NCT03219164.",

keywords = "Aztreonam, Cystic fibrosis, Eradication, Paediatric, Pseudomonas aeruginosa, Respiratory infections, Humans, Administration, Inhalation, Treatment Outcome, Aztreonam/adverse effects, Adolescent, Pseudomonas Infections/diagnosis, Anti-Bacterial Agents/therapeutic use, Child, Cystic Fibrosis/diagnosis",

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

note = "Copyright {\textcopyright} 2023. Published by Elsevier B.V.",

year = "2024",

month = jan,

doi = "10.1016/j.jcf.2023.06.008",

language = "English",

volume = "23",

pages = "80--86",

journal = "Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society",

issn = "1569-1993",

publisher = "Elsevier BV",

number = "1",

}

TY - JOUR

T1 - ALPINE2

T2 - Efficacy and safety of 14-day vs 28-day inhaled aztreonam for Pa eradication in children with cystic fibrosis

AU - Gilchrist, Francis J

AU - Bui, Stephanie

AU - Gartner, Silvia

AU - McColley, Susanna A

AU - Tiddens, Harm

AU - Ruiz, Gary

AU - Stehling, Florian

AU - Alani, Muhsen

AU - Gurtovaya, Oksana

AU - Bresnik, Mark

AU - Watkins, Timothy R

AU - Frankovic, Biliana

AU - Skov, Marianne

AU - ALPINE2 study investigators

PY - 2024/1

Y1 - 2024/1

N2 - 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.

AB - 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.

KW - Aztreonam

KW - Cystic fibrosis, Eradication

KW - Paediatric

KW - Pseudomonas aeruginosa

KW - Respiratory infections

KW - Humans

KW - Administration, Inhalation

KW - Treatment Outcome

KW - Aztreonam/adverse effects

KW - Adolescent

KW - Pseudomonas Infections/diagnosis

KW - Anti-Bacterial Agents/therapeutic use

KW - Child

KW - Cystic Fibrosis/diagnosis

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U2 - 10.1016/j.jcf.2023.06.008

DO - 10.1016/j.jcf.2023.06.008

M3 - Journal article

C2 - 37455237

SN - 1569-1993

VL - 23

SP - 80

EP - 86

JO - Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

JF - Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

IS - 1

ER -

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

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