Effect of evening vs. morning LAMA administration on risk of intensive care admission in COPD patients: influence of adherence post hoc analysis of the randomized controlled trial - LAMA BY NIGHT.

Abstract

Background: The timing of LAMA administration, prescribed for morning dosing, has been questioned, particularly given the nocturnal symptoms many COPD patients experience. The LAMA BY NIGHT trial investigated the impact of LAMA dosing timing (morning vs. evening) on patient-related outcomes, and found no significant effect on risk of exacerbation, but a significant association with ICU admissions. This post hoc analysis of the LAMA BY NIGHT trial explored this association further according to adherence to administration time.

Objective: To determine whether the administration timing of LAMA affects the risk of ICU admission for COPD patients.

Methods: The LAMA BY NIGHT trial was a digital, multicenter, randomized, open-label study that enrolled 10,011 COPD patients. Adherence was measured at 6 and 12 months, with patients considered adherent if they used LAMA at least 6 days a week at the prescribed time. ICU admissions were tracked over 12-months, and relative risks (RR) were calculated to compare admission rates between morning and evening dosing groups. The analysis was stratified by adherence, to assess the sensitivity of the results.

Results: At 6 months, 6,747 patients (67%) completed follow-up questionnaires, of whom 80% were adherent. The risk of ICU admission was numerically lower in the evening dosing group among adherent patients (14/2,302 vs. 24/3,056, RR = 0.77, CI = (0.61-1.55), p = 0.55). At 12 months, ICU admissions were similar between groups (RR = 0.97, CI = (0.40-1.50), p = 1.00). Likewise, non-adherent patients showed no significant difference in ICU admissions between morning and evening dosing at 6 months or 12 months.

Conclusion: In this post hoc analysis of the LAMA BY NIGHT trial, evening administration of LAMA did not reduce the risk of ICU admissions among patients with COPD, and adherence to the assigned dosing schedule did not modify this association.