Optimal Inhalation Therapy for Chronic Obstructive Pulmonary Disease(COPD) Patients

Randomized Comparisons of Morning Versus Bedtime Drug Administration: Optimal Inhalation Therapy for COPD- and Asthma Patients

The primary objective of the study is to examine whether long-acting muscarinic antagonist (LAMA) administration at bedtime versus in the morning leads to a reduction in severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD) among COPD-patients who are already receiving treatment with LAMAs. The hypothesis is that bedtime administration of LAMA, as opposed to morning administration, will lead to fewer severe AECOPD. Further, bedtime administration of LAMA will lead to fewer moderate AECOPD´s, fewer ICU admissions and a lower mortality in COPD patients who are already using LAMAs.

The study is a pragmatic, registry-based, open-label, randomized controlled trial combining the utilization of the Danish nationwide health registries and the official Danish electronic letter system (Digital Post/e-Boks) into an innovative, decentralized trial requiring no study visits from participants. The nationwide health registries will be used for identification of potential participants and data collection including baseline information and follow-up data, while the electronic letter system will be used for sending recruitment letters and communicating with participants. Study participants will provide electronic informed consent from home before inclusion and randomization. The study aims to include approximately minimum 20,000 participants. Participants will be individually randomized 1:1 to either LAMA administration at bedtime or in the morning for 12 months. Adherence with the intervention will be assessed using questionnaires at months 6 and 12. The study will comply with the standards of the CONSORT statement. This study will be conducted by the Chronic Obstructive Pulmonary Disease Trial Network (COP:TRIN) at the Section of Respiratory Medicine, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark, who will be responsible for all processes in the study including recruitment, inclusion, randomization, follow-up, and communication with participants. Registry data will be obtained through the Danish Health Data Authority and accessed through an encrypted remote-access server environment. The trial is expected to start in January/February 2023 and run for 12 months. Via links sent to their official electronic mailbox (Digital Post/e-Boks), trial participants will provide consent and answer questionnaires. Data obtained from these include personal identification number (the CPR-number), electronic signature, select sociodemographic and lifestyle-related variables, and information on compliance with the intervention. All data stemming from these processes will be stored in a REDCap database. All other data collection will be done using the Danish nationwide registries. In collaboration with the Danish Health Data Authority, the personal identification numbers of each participant will be used to link the study database to the Danish nationwide administrative health registries. The Danish National Patient Registry contains information on all in- and outpatient visits in the Danish public health system. The Danish National Prescription Registry contains claimed prescriptions at all pharmacies in Denmark. The Danish Civil Registration System contains information on date of birth, deaths, immigration, and emigration. The Danish Registry of Causes of death can be used to retrieve specific causes of death. Baseline information will be collected from the previously mentioned registries from the date of inclusion up to 10 years prior to the randomization date as has been done in most previous Danish registry-based studies.

Participants will be individually randomized 1:1 to either LAMA administration at bedtime or in the morning for 12 months. Randomization groups will be allocated according to a computer-generated randomization list with random permuted blocks. The result of the randomization will be shown directly to the participant on their screen and sent to the participant's official electronic mailbox.

Investigators will be blinded for the treatment allocation, but the trial participants will not be blinded. However, since all endpoints are assessed using prespecified registry-based definitions, bias should be negligible.

Patients randomized to this group will be instructed to take their LAMA medication as per usual in the morning (approx. 6-9 AM).

Patients randomized to this group will be instructed to take their LAMA medication at bedtime (approx. 8-10 PM)

Inclusion Criteria: Age more than or equal to 30 years Current treatment with LAMA once daily (as recorded in the Danish National Prescription Registry and confirmed by the participant via questionnaire) Exclusion Criteria: 1. Patients who declined to participate.