Once Daily Long-Acting Muscarinic Antagonists Administered in the Evening for Prevention of Chronic Obstructive Pulmonary Disease Exacerbations Requiring Hospitalization or Death From Any Cause

COPD Exacerbation Clinical Trial

Official title:

Comparing Morning and Evening Dosing of Inhaled Long-Acting Muscarinic Antagonists for the Prevention of Hospitalization Requiring AECOPD or Death From All Causes - The LAMA By Night Study Utilizing a Comprehensive Nationwide Digital Platform for Recruitment Into a Pragmatic Randomized Controlled Trial Integrated With National Registries to Follow Outcomes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05563675
• Other study ID #: Protocol_LAMA
• Status: Recruiting
• Phase: Phase 4
• Start date: January 27, 2023
• Est. completion date: June 1, 2024

Study information

• Verified date: February 2024
• Source: Chronic Obstructive Pulmonary Disease Trial Network, Denmark
• Contact: Jens Ulrik Stæhr Jensen, Professor
• Phone: +4538673057
• Email: jens.ulrik.jensen[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To examine, among once-daily LAMA using COPD patients, whether evening administration of LAMA is superior with respect to the incidence of hospitalization requiring AECOPD or death from all causes than the more conventional morning administration.

Description:

One of the most feared complications associated with chronic obstructive pulmonary disease (COPD) is acute exacerbation (AECOPD). On average, each COPD patient experiences 0.5 to 3.5 acute exacerbations per year, which is an important reason for the hospitalization, disease progression and mortality as well as decline in health status and lung function(1,2).

Treatment with a long-acting muscarinic antagonist (LAMA) reduces dyspnoea and the risk of exacerbations in patients with COPD by binding to muscarinic receptors in bronchial smooth musculature and thus inhibiting cholinergic bronchial constriction. LAMAs are given as inhalation therapy once daily (most often) or twice daily(3).

Most COPD-patients experience their worst symptoms and experience exacerbations in early morning hours, before getting out of bed(4). This might be explained by the physiological diurnal changes in the activity of the parasympathetic homeostasis system since this is most active at night to improve digestion and other secretions(5).

Correspondingly, the activity of the sympathetic system is physiologically suppressed at night, and stimulation of β-2 receptors is thus also low (and opposite for M-3 receptors). Taken together, the balance of sympathetic-parasympathetic tone is shifted significantly towards the latter. Most available LAMA treatments are dosed once daily in the morning.

Thus, for a COPD patient, being at a trough level of LAMA (which antagonizes the para-sympathetic system) at late night/early morning, may carry a hazard for the patient.

Studies have found that lung function measured as forced expiratory volume in 1 second (FEV1) improvement peaks approximately 2 hours after LAMA administration, and that FEV1 is still significantly improved at 7 hours post treatment but decreases towards the trough level of the LAMA(6). However, as a corollary to the above, when the medicine is probably most needed (02.00 a.m. to 07.00 a.m.), the effect is at its lowest level, which may not be desirable, since a low effect of the most important preventive medicine against AECOPD at this time, may lead to more exacerbations.

Evening administration, on the contrary, would lead to a greater and more certain effect regarding bronchodilation and reduced secretion in the early morning hours, and a maximum effect should be expected during the entire night.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20000
• Est. completion date: June 1, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

Inclusion Criteria:

1. Age more than or equal to 30 years

2. Current treatment with LAMA once daily (as recorded in the Danish National Prescription Registry and confirmed by the participant via questionnaire)

3. Self-reported COPD

Exclusion Criteria:

1. Patients who decline to participate.

Related Conditions & MeSH terms

• COPD Exacerbation

Intervention

Drug:
• Long acting muscarinic antagonists (LAMAs) in the evening
LAMAs administered at bedtime (8pm - 2am)

Locations

Country	Name	City	State
Denmark	Herlev-Gentofte Hospital	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Chronic Obstructive Pulmonary Disease Trial Network, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	COPD-related hospitalization-requiring (severe) exacerbations		12 months from randomization
Primary	All-cause mortality		12 months from randomization
Secondary	Moderate, non-hospitalization-requiring COPD exacerbations		12 months from randomization
Secondary	Number of admissions for all causes		12 months from randomization
Secondary	Number of admissions in the intensive care unit (ICU) for all causes		12 months from randomization
Secondary	Number of admissions requiring non-invasive ventilation (NIV) treatment		12 months from randomization
Secondary	Mortality (all-cause)		12 months from randomization
Secondary	Use of short-acting ß2-agonists (SABA); pick-up rate	Data collected from the Danish National Prescription Registry	12 months from randomization
Secondary	Change in COPD assesment test (CAT) score	Measured by questionnaire at 6 and 12 months post-randomization. Measured on a scale from 0 to 40. Score of 0-9 means low impact of COPD and score of 31-40 means very high impact.	12 months from randomization
Secondary	Change in medical research council (MRC) score	Measured by questionnaire at 6 and 12 months post-randomization. Measures baseline functional disability due to dyspnoea on a scale from 0 to 5, 0 meaning no disability and 5 meaning significant disability due to COPD.	12 months from randomization