AM/PM dosing of LAMA for COPD: a randomized controlled trial protocol using digital recruitment and registries

Pradeesh Sivapalan*, Valdemar Rømer, Tobias Wirenfeldt Klausen, Niklas Dyrby Johansen, Manan Pareek, Daniel Modin, Alexander Mathioudakis, Jørgen Vestbo, Josefin Eklöf, Alexander Jordan, John R. Hurst, Tor Biering-Sørensen, Jens Ulrik Jensen

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Article number1430169
JournalFrontiers in Medicine
Volume11
Number of pages8
ISSN2296-858X
DOIs
Publication statusPublished - 2024

Bibliographical note

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

Keywords

  • all-cause mortality
  • chronic obstructive pulmonary disease
  • COPD exacerbation
  • intensive care admission
  • long-acting muscarinic antagonists

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