Airway Effects of Tiotropium in Patients With COPD | NCT02683668

NCT02683668

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Boehringer Ingelheim	INDUSTRY

Description Module

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.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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	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)	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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Handihaler-Tiotropium 18 mcg untrained	Combination Product	We are looking at the untrained used of Handihaler	Handihaler-Tiotropium 18 mcg untrained

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	28 days

Secondary Outcomes

Measure	Description	Time Frame
Sacin	Multiple Breath Nitrogen Washout (MBNW). Sacin is a gas exchange measures, assessing convectional ventilation heterogeneity in pre acinar/acinar airways.	28 days
Lung Function FEV1	Lung function parameters FEV1

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.
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.

Name	Affiliation	Role
Omar Usmani	Imperial College London	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Asthma Lab, Royal Brompton Hospital		London		SW36LY	United Kingdom

Arm/Group Information

ID	Title	Description
FG000	Handihaler-Tiotropium 18 mcg Untrained	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 Handihaler-Tiotropium 18 mcg untrained: We are looking at the untrained used of Handihaler
FG001	Handihaler-Tiotropium 18 mcg Trained	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) Handihaler-Tiotropium 18 mcg trained: We are looking at the trained use of Handihaler after 14 days treatment
FG002	Respimat-Tiotropium 5 mcg Trained	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. Respimat-Tiotropium 5 mcg trained: we are looking at the trained use of Respimat after 14 days treatment

Baseline Characteristics Module

ID	Title	Description
BG000	All Participant	Patients receiving Handihaler who have not been trained (real-life use) for over 3 months on its use.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Posted

Mean

Full Range

kPa/l/s

28 days

ID	Title	Description
OG000	Handihaler-Tiotropium 18 mcg Untrained	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 Handihaler-Tiotropium 18 mcg untrained: We are looking at the untrained used of Handihaler

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	All Participant	Patients receiving Handihaler who have not been trained (real-life use) for over 3 months on its use.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 1, 2016	May 15, 2019	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Sep 1, 2016	May 15, 2019	SAP_001.pdf

ID	Term
D029424	Pulmonary Disease, Chronic Obstructive
D008173	Lung Diseases, Obstructive

ID	Term
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes