Design and rationale of the AIR-NET trial: a randomised, open-label, multifactorial, multicentre, adaptive platform trial using a range of repurposed anti-inflammatory treatments to improve outcomes in patients with bronchiectasis within the EMBARC clinical research network

TY - JOUR

T1 - Design and rationale of the AIR-NET trial

T2 - a randomised, open-label, multifactorial, multicentre, adaptive platform trial using a range of repurposed anti-inflammatory treatments to improve outcomes in patients with bronchiectasis within the EMBARC clinical research network

AU - Long, Merete B.

AU - New, Jaa Ming

AU - Stobo, Jamie

AU - Band, Margaret

AU - Mclaren-Neil, Fiona

AU - Hull, Rebecca

AU - Gilmour, Amy

AU - Lind, Holly

AU - McIntosh, Eve

AU - Galloway, Rachel

AU - Eke, Zsofia

AU - Harris, Bridget

AU - Singanayagam, Aran

AU - Shah, Anand

AU - Huang, Jeffrey

AU - Wilkinson, Tom

AU - Loebinger, Michael R.

AU - Haworth, Charles S.

AU - Chotirmall, Sanjay H.

AU - de Soyza, Anthony

AU - Chalmers, James D.

N1 - Publisher Copyright: © The authors 2026.

PY - 2026/3/9

Y1 - 2026/3/9

N2 - Background Neutrophilic airway inflammation is associated with disease severity and exacerbation frequency in bronchiectasis. Neutrophil protease inhibition significantly reduced exacerbation rates in phase II and III trials in bronchiectasis, highlighting this disease feature as an important therapeutic target. Additional neutrophil targeting therapeutics are needed to reduce the burden of the disease. Herein, we describe the protocol for the AIR-NET trial, the first randomised, open-label, multifactorial, multicentre, adaptive platform trial for people with bronchiectasis, run via the EMBARC (European Multicentre Bronchiectasis Audit and Research Collaboration) network, to investigate the safety and efficacy of several repurposed anti-inflammatory treatments. Methods and analysis Participants with bronchiectasis confirmed by computed tomography, daily sputum production and evidence of active airway neutrophilic inflammation (based on a positive lateral flow test for neutrophil elastase (NE) activity), across 10 sites in the UK, will be randomised to one of several repurposed drugs with published evidence of effects on neutrophilic inflammation and acceptable safety profile (oral dose: disulfiram 400 mg once daily; dipyridamole 200 mg twice daily; doxycycline 100 mg once daily; n=42 per arm) or usual care, according to arm-specific eligibility criteria, and treated for 28 days. New arms will be added to the trial through an adaptive design. The primary end-point is change from baseline in sputum NE activity (a validated biomarker and surrogate of exacerbation risk) at day 28. Key secondary end-points include time-to-first exacerbation, quality of life questionnaires, neutrophil function and safety. Summary AIR-NET will establish a multi-centre network with integrated clinical and translational capabilities for the investigation of therapies in bronchiectasis aiming to identify key anti-inflammatory mechanisms and effective re-purposed treatments.

AB - Background Neutrophilic airway inflammation is associated with disease severity and exacerbation frequency in bronchiectasis. Neutrophil protease inhibition significantly reduced exacerbation rates in phase II and III trials in bronchiectasis, highlighting this disease feature as an important therapeutic target. Additional neutrophil targeting therapeutics are needed to reduce the burden of the disease. Herein, we describe the protocol for the AIR-NET trial, the first randomised, open-label, multifactorial, multicentre, adaptive platform trial for people with bronchiectasis, run via the EMBARC (European Multicentre Bronchiectasis Audit and Research Collaboration) network, to investigate the safety and efficacy of several repurposed anti-inflammatory treatments. Methods and analysis Participants with bronchiectasis confirmed by computed tomography, daily sputum production and evidence of active airway neutrophilic inflammation (based on a positive lateral flow test for neutrophil elastase (NE) activity), across 10 sites in the UK, will be randomised to one of several repurposed drugs with published evidence of effects on neutrophilic inflammation and acceptable safety profile (oral dose: disulfiram 400 mg once daily; dipyridamole 200 mg twice daily; doxycycline 100 mg once daily; n=42 per arm) or usual care, according to arm-specific eligibility criteria, and treated for 28 days. New arms will be added to the trial through an adaptive design. The primary end-point is change from baseline in sputum NE activity (a validated biomarker and surrogate of exacerbation risk) at day 28. Key secondary end-points include time-to-first exacerbation, quality of life questionnaires, neutrophil function and safety. Summary AIR-NET will establish a multi-centre network with integrated clinical and translational capabilities for the investigation of therapies in bronchiectasis aiming to identify key anti-inflammatory mechanisms and effective re-purposed treatments.

UR - https://www.scopus.com/pages/publications/105033958694

U2 - 10.1183/23120541.00719-2025

DO - 10.1183/23120541.00719-2025

M3 - Article

C2 - 41809869

AN - SCOPUS:105033958694

SN - 2312-0541

VL - 12

JO - ERJ Open Research

JF - ERJ Open Research

IS - 2

M1 - 00719-2025

ER -