COPDPhase 3NCT02683668

Airway Effects of Tiotropium in Patients With COPD

A Phase 3 study testing Handihaler-Tiotropium 18 mcg untrained, Handihaler-Tiotropium 18 mcg trained and Respimat-Tiotropium 5 mcg trained in people with COPD and LUNG DISEASES, OBSTRUCTIVE, run by Imperial College London at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 30 years and older
Conditions the study is for: COPD, LUNG DISEASES, OBSTRUCTIVE
What is being tested?: Handihaler-Tiotropium 18 mcg untrained, Handihaler-Tiotropium 18 mcg trained and Respimat-Tiotropium 5 mcg trained
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 44 participants
Where: 1 siteUnited Kingdom
Study dates: 1 Feb 2016to 1 Jan 2018
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

COPD patients with FEV1/FVC <70% predicted.
Mild (GOLD stage I: FEV1 >80% pred.) to moderate (GOLD stage II: FEV1 50-80% pred.)
Aged 30 years onwards - there is no upper age limit as we do not want to exclude elderly patients as COPD is primarily a disease in the elderly population.
Have on-going symptoms or exercise limitation (determined by CAT score)
Stable COPD (no chest infection requiring antibiotics and/or oral steroids in the past 2 months).
Capable of giving informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Who cannot join

Subjects who lack the capacity to consent will not be recruited.
Current or past diagnosis of asthma.
Patients on concurrent oral bronchodilators (theophylline, PDE4 inhibitors) will not be included.
Patients on other LAMAs will not be included
History of any chronic respiratory diseases other than COPD.
History of another medical condition, which in the opinion of the Unit Physician, contraindicates his/her participation in the study.

Show all 16Show fewer

Clinical evidence of heart failure (NYHA class III-IV).
Unstable respiratory disease in the last four weeks prior to the screening visit (indicated by any change in their maintenance inhaled therapy or who have had a lower respiratory tract infection in the previous four weeks).
Evidence of a respiratory exacerbation requiring emergency room treatment and/or hospitalisation within four weeks before screening.
Use of systemic (oral or intravenous) steroids 4 weeks prior to inclusion (injectable depot steroids 6 weeks) or more than 3 periods during the last 12 months.
Participants with a known or suspected allergy, sensitivity or intolerance to the study drugs (this will be asked directly at the screening visit) or patients with a history of another drug allergy which, in the opinion of the Unit Physician, contraindicates his/her participation in the study.
Patients with known or suspected cardiac rhythm disorders
Patients treated with beta-blockers in the week preceding the screening visit and during the study period.
Females who are pregnant or lactating or are likely to become pregnant during the trial. (a urine pregnancy test will be performed. Women of childbearing potential may be included in the study if, in the opinion of the investigator, they are taking adequate contraceptive precautions.
Patients who have evidence of alcohol or substance abuse.
Participation in another clinical trial with an investigational drug in the four weeks preceding the screening visit.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Asthma Lab, Royal Brompton Hospital
London, SW36LY

Other trials in United Kingdom

About this study

Official title: Targeting of the Small Airways in Patients With COPD: Airway Effects of Tiotropium - Respimat vs Handihaler

The aim of the study is to investigate the effect of tiotropium from different devices on a panel of small (IOS, MBNW, DLCO, FVC) and large airway (FEV1, PEF) responses in patients with mild-moderate COPD. Comparisons will be made between Tiotropium Handihaler 18 micrograms once daily and Tiotropium Respimat 5 micrograms once daily

Read the detailed description

Patients with asthma and chronic obstructive airways disease (COPD) undergo routine testing of their lung function in the diagnosis, progression, management and, response to treatment of their disease. Standard lung function obtains measurements based on the forced flow of air moving within the airways. Such measurements give a reasonable assessment of disease affecting the large airways, but not an accurate estimate of small airways disease. Small airways are less than 2mm in diameter. However, both asthma and COPD have disease that involves not only the large but also the small airways that has important clinical consequences. Indeed, COPD predominantly affects the small airways.

Tiotropium (Spiriva, Boehringer Ingelheim), a long-acting inhaled anticholinergic bronchodilator, improves lung function, quality of life, and exercise endurance and reduces exacerbations in patients with chronic obstructive pulmonary disease (COPD).

Respimat Soft MistTM Inhaler (SMI) is a novel inhaler delivering a unique slow-moving Soft MistTM that allows gentle inhalation - making it easy to inhale. Importantly it has drug particles that are ~ 2microns that allow an increase in the total lung deposition of drug (~52%) and also the potential for penetration to treat the small and large airways in patients with COPD; that is targeting the whole airway tree.

RESEARCH AIM \& HYPOTHESIS The aim is to investigate the effect of tiotropium from different devices on a panel of small (IOS, MBNW, DLCO, FVC) and large airway (FEV1, PEF) responses in patients with mild-moderate COPD. The investigators will compare Tiotropium Handihaler 18 micrograms once daily with Tiotropium Respimat 5 micrograms once daily.

The investigators will identify a COPD cohort with ongoing symptoms or exercise limitation on HandiHaler, as proposed. The science behind this is why are people still limited (even if partially as determined using the CAT score) and is more distal airway targeting necessary? This doesn't necessarily mean targeting the acinar/alveolar beyond the terminal bronchioles, but just a little bit deeper into the distal conducting airway. This can be achieved with Respimat.

Conditions: COPD, LUNG DISEASES, OBSTRUCTIVE
Being tested: Handihaler-Tiotropium 18 mcg untrained, Handihaler-Tiotropium 18 mcg trained, Respimat-Tiotropium 5 mcg trained
Keywords: Inhalers, Tiotropium
Medical subject headings: Pulmonary Disease, Chronic Obstructive, Lung Diseases, Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Handihaler-Tiotropium 18 mcg untrainedCombination product
We are looking at the untrained used of Handihaler
Handihaler-Tiotropium 18 mcg trainedCombination product
We are looking at the trained use of Handihaler after 14 days treatment
Respimat-Tiotropium 5 mcg trainedCombination product
we are looking at the trained use of Respimat after 14 days treatment

Study groups in NCT02683668
Study group	Role	What they receive
Handihaler-Tiotropium 18 mcg untrained	Experimental	Patients receiving Handihaler who have not been trained (real-life use) for over 3 months on its use. Here the investigators want to see that if patients have on-going symptoms but are on Handihaler-Tiotropium 18mcg what is happening PRIOR to proper inhaler technique training - that is their 'real-life' use of the inhaler - to their lung function (large and small airways) and also symptoms or exercise limitation (determined by CAT score) will already be recorded as entry criteria Receives: Combination Product: Handihaler-Tiotropium 18 mcg untrained
Handihaler-Tiotropium 18 mcg trained	Experimental	Patients will be trained in their use of Handihaler-Tiotropium and asked to take 18 mcg once daily for 14 days to see if their (i) airway lung function and or (ii) clinical symptoms improve. Here the investigators want to see what happens AFTER proper inhaler technique training on large and small airways lung function and also symptoms or exercise limitation (determined by CAT score) Receives: Combination Product: Handihaler-Tiotropium 18 mcg trained
Respimat-Tiotropium 5 mcg trained	Experimental	Patients will be switched to trained Respimat Tiotropium 5 mcg once daily for 14 days to see if their (i) airway lung function and or (ii) clinical symptoms improve. Here the investigators want to see what happens AFTER this efficient device Respimat (trained) compared to PREVIOUS device Handihaler (trained) on large and small airways lung function and also symptoms or exercise limitation (determined by CAT score). The investigators want to see if the properties of the Respimat device with deeper lung deposition (slow velocity and small particles) can improve small airway measures (and indeed large airway measures) that might also be related to an improvement in symptoms. Receives: Combination Product: Respimat-Tiotropium 5 mcg trained

What is being measured

The primary outcome is the main question the study is designed to answer.

Peripheral Airways Resistance (R5-R20)
Peripheral airways resistance measured by impulse oscillometry (IOS). Specific frequencies relate to different levels: a frequency of 5 hertz (Hz) provides values for total airway resistance (R5) and reactance (X5); a 20Hz frequency gives a value for central or large airway resistance (R20); and if one subtracts the value of central airway resistance from that for total airway resistance (i.e. R5-R20), this provides a measure of peripheral or small airways resistance.
Measured: 28 days

Secondary outcomes (3)

Sacin
Multiple Breath Nitrogen Washout (MBNW). Sacin is a gas exchange measures, assessing convectional ventilation heterogeneity in pre acinar/acinar airways.
Measured: 28 days
Lung Function FEV1
Lung function parameters FEV1
Measured: 28 days
Scond
MBW parameters. Scond is a gas exchange measures, assessing convectional ventilation heterogeneity in peripheral conducting airways.
Measured: 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Feb 20161 Jan 2018

First posted17 Feb 2016 (estimated)
Study start1 Feb 2016
Primary completion1 Jan 2018
Study completion1 Jan 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for COPDStudies of the same condition, open and under way.
More trials run by Imperial College LondonThe sponsor's other registered studies.
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 3
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Model description: Each volunteer get all treatment in a same sequence
Masking: None (open label)
Enrolment: 44 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02683668
Sponsor's protocol ID: 151C2697
Status last verified: Aug 2025
First submitted: 11 Feb 2016
Last updated: 29 Aug 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All COPD trials

Study at a glance

From the registry record, last updated by the sponsor on 29 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Targeting of the Small Airways in Patients With COPD: Airway Effects of Tiotropium - Respimat vs Handihaler
ClinicalTrials.gov ID: NCT02683668
Acronym / sponsor ID: 151C2697
Conditions: COPD, LUNG DISEASES, OBSTRUCTIVE
Keywords: Inhalers, Tiotropium
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 44 participants (actual)
Lead sponsor: Imperial College LondonUniversity, hospital or other
Collaborators: Boehringer Ingelheim
Study start: 1 Feb 2016 (actual)
Primary completion: 1 Jan 2018 (actual)
Study completion: 1 Jan 2018 (actual)
First posted: 17 Feb 2016 (estimated)
Results: Posted 12 Nov 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 3
Model description: Each volunteer get all treatment in a same sequence

Arm	Type	Receives
Handihaler-Tiotropium 18 mcg untrained	Experimental	Combination Product: Handihaler-Tiotropium 18 mcg untrainedPatients receiving Handihaler who have not been trained (real-life use) for over 3 months on its use. Here the investigators want to see that if patients have on-going symptoms but are on Handihaler-Tiotropium 18mcg what is happening PRIOR to proper inhaler technique training - that is their 'real-life' use of the inhaler - to their lung function (large and small airways) and also symptoms or exercise limitation (determined by CAT score) will already be recorded as entry criteria
Handihaler-Tiotropium 18 mcg trained	Experimental	Combination Product: Handihaler-Tiotropium 18 mcg trainedPatients will be trained in their use of Handihaler-Tiotropium and asked to take 18 mcg once daily for 14 days to see if their (i) airway lung function and or (ii) clinical symptoms improve. Here the investigators want to see what happens AFTER proper inhaler technique training on large and small airways lung function and also symptoms or exercise limitation (determined by CAT score)
Respimat-Tiotropium 5 mcg trained	Experimental	Combination Product: Respimat-Tiotropium 5 mcg trainedPatients will be switched to trained Respimat Tiotropium 5 mcg once daily for 14 days to see if their (i) airway lung function and or (ii) clinical symptoms improve. Here the investigators want to see what happens AFTER this efficient device Respimat (trained) compared to PREVIOUS device Handihaler (trained) on large and small airways lung function and also symptoms or exercise limitation (determined by CAT score). The investigators want to see if the properties of the Respimat device with deeper lung deposition (slow velocity and small particles) can improve small airway measures (and indeed large airway measures) that might also be related to an improvement in symptoms.

Who may qualify

Ages: 30 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

COPD patients with FEV1/FVC <70% predicted.
Mild (GOLD stage I: FEV1 >80% pred.) to moderate (GOLD stage II: FEV1 50-80% pred.)
Aged 30 years onwards - there is no upper age limit as we do not want to exclude elderly patients as COPD is primarily a disease in the elderly population.
Have on-going symptoms or exercise limitation (determined by CAT score)
Stable COPD (no chest infection requiring antibiotics and/or oral steroids in the past 2 months).

Key exclusion criteria (16 listed)

Subjects who lack the capacity to consent will not be recruited.
Current or past diagnosis of asthma.
Patients on concurrent oral bronchodilators (theophylline, PDE4 inhibitors) will not be included.
Patients on other LAMAs will not be included
History of any chronic respiratory diseases other than COPD.

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
Handihaler-Tiotropium 18 mcg untrainedWe are looking at the untrained used of Handihaler	Combination product	Handihaler-Tiotropium 18 mcg untrained
Handihaler-Tiotropium 18 mcg trainedWe are looking at the trained use of Handihaler after 14 days treatment	Combination product	Handihaler-Tiotropium 18 mcg trained
Respimat-Tiotropium 5 mcg trainedwe are looking at the trained use of Respimat after 14 days treatment	Combination product	Respimat-Tiotropium 5 mcg trained

Primary outcome

Peripheral Airways Resistance (R5-R20)
Time frame: 28 days
Peripheral airways resistance measured by impulse oscillometry (IOS). Specific frequencies relate to different levels: a frequency of 5 hertz (Hz) provides values for total airway resistance (R5) and reactance (X5); a 20Hz frequency gives a value for central or large airway resistance (R20); and if one subtracts the value of central airway resistance from that for total airway resistance (i.e. R5-R20), this provides a measure of peripheral or small airways resistance.

3 secondary outcomes

Sacin
Time frame: 28 days
Lung Function FEV1
Time frame: 28 days
Scond
Time frame: 28 days

Results and safety

Results posted to the registry on 12 Nov 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Handihaler-Tiotropium 18 mcg Untrained	44	44
Handihaler-Tiotropium 18 mcg Trained	0	0
Respimat-Tiotropium 5 mcg Trained	0	0

Primary outcome: Peripheral Airways Resistance (R5-R20)

Time frame: 28 days. Mean (Full Range). Unit: kPa/l/s

Measure	Handihaler-Tiotropium 18 mcg Untrained n = 44	Handihaler-Tiotropium 18 mcg Trained n = 43	Respimat-Tiotropium 5 mcg Trained n = 43
Value	0.23 (0.004 to 0.56)	0.2 (0.03 to 0.62)	0.16 (0.03 to 0.42)

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 12 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
All Participant	0 of 43 (0%)	0 of 43 (0%)	0 of 43

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for COPD

Active, not recruiting
Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
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An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruiting
The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
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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.

Omar Usmani principal investigator

Imperial College London

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 6 inclusion and 16 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 29 Aug 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 United Kingdom. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Peripheral Airways Resistance (R5-R20) (time frame: 28 days). 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 NCT02683668.

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 29 Aug 2025.