COPD, LUNG DISEASES, OBSTRUCTIVE
Conditions
Keywords
Inhalers, Tiotropium
Brief summary
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
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.
Interventions
COMBINATION_PRODUCTHandihaler-Tiotropium 18 mcg untrained
We are looking at the untrained used of Handihaler
COMBINATION_PRODUCTHandihaler-Tiotropium 18 mcg trained
We are looking at the trained use of Handihaler after 14 days treatment
COMBINATION_PRODUCTRespimat-Tiotropium 5 mcg trained
we are looking at the trained use of Respimat after 14 days treatment
Sponsors
Boehringer Ingelheim
Imperial College London
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Each volunteer get all treatment in a same sequence
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. COPD patients with FEV1/FVC \<70% predicted. 2. Mild (GOLD stage I: FEV1 \>80% pred.) to moderate (GOLD stage II: FEV1 50-80% pred.) 3. 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. 4. Have on-going symptoms or exercise limitation (determined by CAT score) 5. Stable COPD (no chest infection requiring antibiotics and/or oral steroids in the past 2 months). 6. Capable of giving informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Exclusion criteria
1. Subjects who lack the capacity to consent will not be recruited. 2. Current or past diagnosis of asthma. 3. Patients on concurrent oral bronchodilators (theophylline, PDE4 inhibitors) will not be included. 4. Patients on other LAMAs will not be included 5. History of any chronic respiratory diseases other than COPD. 6. History of another medical condition, which in the opinion of the Unit Physician, contraindicates his/her participation in the study. 7. Clinical evidence of heart failure (NYHA class III-IV). 8. 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). 9. Evidence of a respiratory exacerbation requiring emergency room treatment and/or hospitalisation within four weeks before screening. 10. 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. 11. 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. 12. Patients with known or suspected cardiac rhythm disorders 13. Patients treated with beta-blockers in the week preceding the screening visit and during the study period. 14. 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. 15. Patients who have evidence of alcohol or substance abuse. 16. Participation in another clinical trial with an investigational drug in the four weeks preceding the screening visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peripheral Airways Resistance (R5-R20) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sacin | 28 days | Multiple Breath Nitrogen Washout (MBNW). Sacin is a gas exchange measures, assessing convectional ventilation heterogeneity in pre acinar/acinar airways. |
| Lung Function FEV1 | 28 days | Lung function parameters FEV1 |
| Scond | 28 days | MBW parameters. Scond is a gas exchange measures, assessing convectional ventilation heterogeneity in peripheral conducting airways. |
Countries
United Kingdom
Participant flow
Recruitment details
Forty-four subjects (23 male) with mild-to-moderate COPD (GOLD stage I-II, FEV1 67.8% of predicted) using DPI-HandiHaler (18µg tiotropium daily) for at least 3 months, but with ongoing symptoms or exercise limitation (COPD Assesment Test (CAT) score \>10) participated in the study. 1 failed to complete
Participants by arm
| Arm | Count |
|---|---|
| All Participant Patients receiving Handihaler who have not been trained (real-life use) for over 3 months on its use. | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period 2 | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | All Participant | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 32 Participants | — |
| Age, Categorical Between 18 and 65 years | 12 Participants | — |
| Age, Continuous | 69.1 years STANDARD_DEVIATION 8 | — |
| R5 - R20 (Peripheral Airways Resistance) | 0.608 kPa/l/s STANDARD_DEVIATION 0.207 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United Kingdom | 44 participants | — |
| Sex: Female, Male Female | 21 Participants | — |
| Sex: Female, Male Male | 23 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 43 |
| other Total, other adverse events | 0 / 43 |
| serious Total, serious adverse events | 0 / 43 |
Outcome results
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.
Time frame: 28 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Handihaler-Tiotropium 18 mcg Untrained | Peripheral Airways Resistance (R5-R20) | 0.23 kPa/l/s |
| Handihaler-Tiotropium 18 mcg Trained | Peripheral Airways Resistance (R5-R20) | 0.2 kPa/l/s |
| Respimat-Tiotropium 5 mcg Trained | Peripheral Airways Resistance (R5-R20) | 0.16 kPa/l/s |
Secondary
Lung Function FEV1
Lung function parameters FEV1
Time frame: 28 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Handihaler-Tiotropium 18 mcg Untrained | Lung Function FEV1 | 1.575 liters |
| Handihaler-Tiotropium 18 mcg Trained | Lung Function FEV1 | 1.58 liters |
| Respimat-Tiotropium 5 mcg Trained | Lung Function FEV1 | 1.651 liters |
Secondary
Sacin
Multiple Breath Nitrogen Washout (MBNW). Sacin is a gas exchange measures, assessing convectional ventilation heterogeneity in pre acinar/acinar airways.
Time frame: 28 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Handihaler-Tiotropium 18 mcg Untrained | Sacin | 0.333 kPa\l\s |
| Handihaler-Tiotropium 18 mcg Trained | Sacin | 0.339 kPa\l\s |
| Respimat-Tiotropium 5 mcg Trained | Sacin | 0.345 kPa\l\s |
Secondary
Scond
MBW parameters. Scond is a gas exchange measures, assessing convectional ventilation heterogeneity in peripheral conducting airways.
Time frame: 28 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Handihaler-Tiotropium 18 mcg Untrained | Scond | 0.05 kPa\l\s |
| Handihaler-Tiotropium 18 mcg Trained | Scond | 0.04 kPa\l\s |
| Respimat-Tiotropium 5 mcg Trained | Scond | 0.04 kPa\l\s |