COPD ExacerbationPhase 4NCT05563675
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
A Phase 4 study testing Long acting muscarinic antagonists (LAMAs) in the evening in people with COPD Exacerbation, run by Chronic Obstructive Pulmonary Disease Trial Network, Denmark at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- COPD Exacerbation
- What is being tested?
- Long acting muscarinic antagonists (LAMAs) in the evening
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10,011 participants
- Where
- 1 siteDenmark
- Study dates
- 27 Jan 2023to 1 Jun 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
- Self-reported COPD
Who cannot join
- 1. Patients who decline to participate.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed 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.
- Conditions
- COPD Exacerbation
- Being tested
- Long acting muscarinic antagonists (LAMAs) in the evening
- Keywords
- LAMA, Bedtime administration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Long acting muscarinic antagonists (LAMAs) in the eveningDrug
LAMAs administered at bedtime (8pm - 2am)
| Study group | Role | What they receive |
|---|---|---|
| Morning administration of LAMA | No intervention | Participants randomized to this group (with or without the combination of ICS and/or LABA) will be instructed to take their LAMA as usual in the morning between 6 and 12am. |
| Bedtime administration of LAMA | Experimental | Participants randomized to this group (with or without the combination of inhaled corticosteroids (ICS) and/or long-acting beta2-agonists (LABA)) will be instructed to take their LAMA-containing inhalation between 8pm. and 2am. Receives: Drug: Long acting muscarinic antagonists (LAMAs) in the evening |
What is being measured
The primary outcome is the main question the study is designed to answer.
COPD-related hospitalization-requiring (severe) exacerbations
Measured: 12 months from randomization
All-cause mortality
Measured: 12 months from randomization
Secondary outcomes (8)
Moderate, non-hospitalization-requiring COPD exacerbations
Measured: 12 months from randomization
Number of admissions for all causes
Measured: 12 months from randomization
Number of admissions in the intensive care unit (ICU) for all causes
Measured: 12 months from randomization
Number of admissions requiring non-invasive ventilation (NIV) treatment
Measured: 12 months from randomization
Mortality (all-cause)
Measured: 12 months from randomization
Use of short-acting β2-agonists (SABA); pick-up rate
Data collected from the Danish National Prescription Registry
Measured: 12 months from randomization
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.
Measured: 12 months from randomization
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.
Measured: 12 months from randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2022
- Study start27 Jan 2023
- Primary completion1 Jun 2024
- Study completion1 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COPD ExacerbationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized 1:1 to one of two treatment strategies by computer-generated allocation, to either LAMA administration in the morning or evening. Randomization groups will be allocated according to a computer-generated randomization. Data will be entered by participants directly into REDCap questionnaires. Consent and randomization will take place on day 0. The result of the randomization will be shown directly to the participant on their screen and sent to the participant's official electronic mailbox.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 10,011 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chronic Obstructive Pulmonary Disease Trial Network, Denmark
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05563675
- Sponsor's protocol ID
- Protocol_LAMA
- Status last verified
- Feb 2025
- First submitted
- 23 Sep 2022
- Last updated
- 19 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Both negative, positive, and inconclusive results will be submitted for publication in peer-reviewed journals and presented at international scientific conferences. Participant-level data and statistical code will not be published.
Publications
Sivapalan P, Romer V, Jordan A, Johansen ND, Pareek M, Modin D, Mathioudakis AG, Vestbo J, Vognsen AK, Eklof J, Hurst JR, Klausen TW, Biering-Sorensen T, Jensen JS. Evening administration of long-acting muscarinic antagonists in COPD - a randomized controlled trial. BMC Pulm Med. 2025 Dec 3;25(1):552. doi: 10.1186/s12890-025-03952-y.
PubMed 41340061Sivapalan P, Romer V, Wirenfeldt Klausen T, Dyrby Johansen N, Pareek M, Modin D, Mathioudakis A, Vestbo J, Eklof J, Jordan A, Hurst JR, Biering-Sorensen T, Jensen JU. AM/PM dosing of LAMA for COPD: a randomized controlled trial protocol using digital recruitment and registries. Front Med (Lausanne). 2024 Aug 6;11:1430169. doi: 10.3389/fmed.2024.1430169. eCollection 2024.
PubMed 39165373
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05563675
- Acronym / sponsor ID
- Protocol_LAMA
- Conditions
- COPD Exacerbation
- Keywords
- LAMA, Bedtime administration
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10,011 participants (actual)
- Lead sponsor
- Chronic Obstructive Pulmonary Disease Trial Network, DenmarkUniversity, hospital or other
- Study start
- 27 Jan 2023 (actual)
- Primary completion
- 1 Jun 2024 (actual)
- Study completion
- 1 Jun 2024 (actual)
- First posted
- 3 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Patients will be randomized 1:1 to one of two treatment strategies by computer-generated allocation, to either LAMA administration in the morning or evening. Randomization groups will be allocated according to a computer-generated randomization. Data will be entered by participants directly into REDCap questionnaires. Consent and randomization will take place on day 0. The result of the randomization will be shown directly to the participant on their screen and sent to the participant's official electronic mailbox.
| Arm | Type | Receives |
|---|---|---|
| Morning administration of LAMA | No intervention | –Participants randomized to this group (with or without the combination of ICS and/or LABA) will be instructed to take their LAMA as usual in the morning between 6 and 12am. |
| Bedtime administration of LAMA | Experimental | Drug: Long acting muscarinic antagonists (LAMAs) in the eveningParticipants randomized to this group (with or without the combination of inhaled corticosteroids (ICS) and/or long-acting beta2-agonists (LABA)) will be instructed to take their LAMA-containing inhalation between 8pm. and 2am. |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
- Self-reported COPD
Key exclusion criteria (1 listed)
- 1. Patients who decline to participate.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Long acting muscarinic antagonists (LAMAs) in the eveningLAMAs administered at bedtime (8pm - 2am) | Drug | Bedtime administration of LAMA |
Primary outcome
COPD-related hospitalization-requiring (severe) exacerbations
Time frame: 12 months from randomization
All-cause mortality
Time frame: 12 months from randomization
8 secondary outcomes
Moderate, non-hospitalization-requiring COPD exacerbations
Time frame: 12 months from randomization
Number of admissions for all causes
Time frame: 12 months from randomization
Number of admissions in the intensive care unit (ICU) for all causes
Time frame: 12 months from randomization
Number of admissions requiring non-invasive ventilation (NIV) treatment
Time frame: 12 months from randomization
Mortality (all-cause)
Time frame: 12 months from randomization
Use of short-acting β2-agonists (SABA); pick-up rate
Time frame: 12 months from randomization
Change in COPD assesment test (CAT) score
Time frame: 12 months from randomization
Change in medical research council (MRC) score
Time frame: 12 months from randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2025.
- Derived from this study: PubMed 41340061Sivapalan P, Romer V, Jordan A, Johansen ND, Pareek M, Modin D, Mathioudakis AG, Vestbo J, Vognsen AK, Eklof J, Hurst JR, Klausen TW, Biering-Sorensen T, Jensen JS. Evening administration of long-acting muscarinic antagonists in COPD - a randomized controlled trial. BMC Pulm Med. 2025 Dec 3;25(1):552. doi: 10.1186/s12890-025-03952-y.
- Derived from this study: PubMed 39165373Sivapalan P, Romer V, Wirenfeldt Klausen T, Dyrby Johansen N, Pareek M, Modin D, Mathioudakis A, Vestbo J, Eklof J, Jordan A, Hurst JR, Biering-Sorensen T, Jensen JU. AM/PM dosing of LAMA for COPD: a randomized controlled trial protocol using digital recruitment and registries. Front Med (Lausanne). 2024 Aug 6;11:1430169. doi: 10.3389/fmed.2024.1430169. eCollection 2024.
- Individual participant dataSharing planned: No. Both negative, positive, and inconclusive results will be submitted for publication in peer-reviewed journals and presented at international scientific conferences. Participant-level data and statistical code will not be published.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Long acting muscarinic antagonists (LAMAs) in the evening in people with COPD Exacerbation, run by Chronic Obstructive Pulmonary Disease Trial Network, Denmark at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
COPD-related hospitalization-requiring (severe) exacerbations (time frame: 12 months from randomization). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05563675, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2025.