TY - JOUR

T1 - AM/PM dosing of LAMA for COPD

T2 - a randomized controlled trial protocol using digital recruitment and registries

AU - Sivapalan, Pradeesh

AU - Rømer, Valdemar

AU - Klausen, Tobias Wirenfeldt

AU - Johansen, Niklas Dyrby

AU - Pareek, Manan

AU - Modin, Daniel

AU - Mathioudakis, Alexander

AU - Vestbo, Jørgen

AU - Eklöf, Josefin

AU - Jordan, Alexander

AU - Hurst, John R.

AU - Biering-Sørensen, Tor

AU - Jensen, Jens Ulrik

N1 - Publisher Copyright: Copyright © 2024 Sivapalan, Rømer, Wirenfeldt Klausen, Dyrby Johansen, Pareek, Modin, Mathioudakis, Vestbo, Eklöf, Jordan, Hurst, Biering-Sørensen and Jensen.

PY - 2024

Y1 - 2024

N2 - Rationale: Long-acting muscarinic antagonists (LAMAs) reduce the risk of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), usually taken once daily in the morning. However, the circadian activity of autonomic regulation suggests that the highest need for anticholinergic therapy may be in the late night/early morning. This is supported by evidence that AECOPD most often begins in the morning. Furthermore, the trough spirometry effect of LAMA is lower than the peak effect, which further argues that evening dosing may be more optimal than morning dosing. This trial aims to determine whether evening administration of LAMA reduces hospitalization-requiring AECOPD or death from all causes within 1 year as compared to morning administration of the same LAMA. Methods: Randomized controlled open-label trial. Persons aged 30 years or older with a once-daily LAMA prescription and a confirmed COPD diagnosis were recruited. Participants were randomized in a 1:1 ratio to either morning or evening LAMA administration. Complete follow-up for the primary outcome, hospitalization-requiring AECOPD, or death from all causes within 1 year was captured from the Danish National Health Register, as were patient-reported outcome assessments at 6 and 12 months. Results: A total of 10,013 participants were randomized, and the recruitment process started on 9 March 2023. Secondary outcomes include (i) moderate COPD exacerbations; (ii) all-cause hospitalization; (iii) ICU admission; (iv) need for non-invasive ventilation; and (v) all-cause mortality, among others. All outcomes will be evaluated 12 months after recruitment. Clinical trial registration:ClinicalTrials.gov, NCT05563675.

AB - Rationale: Long-acting muscarinic antagonists (LAMAs) reduce the risk of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), usually taken once daily in the morning. However, the circadian activity of autonomic regulation suggests that the highest need for anticholinergic therapy may be in the late night/early morning. This is supported by evidence that AECOPD most often begins in the morning. Furthermore, the trough spirometry effect of LAMA is lower than the peak effect, which further argues that evening dosing may be more optimal than morning dosing. This trial aims to determine whether evening administration of LAMA reduces hospitalization-requiring AECOPD or death from all causes within 1 year as compared to morning administration of the same LAMA. Methods: Randomized controlled open-label trial. Persons aged 30 years or older with a once-daily LAMA prescription and a confirmed COPD diagnosis were recruited. Participants were randomized in a 1:1 ratio to either morning or evening LAMA administration. Complete follow-up for the primary outcome, hospitalization-requiring AECOPD, or death from all causes within 1 year was captured from the Danish National Health Register, as were patient-reported outcome assessments at 6 and 12 months. Results: A total of 10,013 participants were randomized, and the recruitment process started on 9 March 2023. Secondary outcomes include (i) moderate COPD exacerbations; (ii) all-cause hospitalization; (iii) ICU admission; (iv) need for non-invasive ventilation; and (v) all-cause mortality, among others. All outcomes will be evaluated 12 months after recruitment. Clinical trial registration:ClinicalTrials.gov, NCT05563675.

KW - all-cause mortality

KW - chronic obstructive pulmonary disease

KW - COPD exacerbation

KW - intensive care admission

KW - long-acting muscarinic antagonists

U2 - 10.3389/fmed.2024.1430169

DO - 10.3389/fmed.2024.1430169

M3 - Journal article

C2 - 39165373

AN - SCOPUS:85201527816

VL - 11

JO - Frontiers in Medicine

JF - Frontiers in Medicine

SN - 2296-858X

M1 - 1430169

ER -