COPD
Conditions
Keywords
Inhaled corticosteroids, COPD, mannitol
Brief summary
Study purpose is to evaluate if subjects with chronic obstructive pulmonary disease (COPD) are more likely to be responsive to additional inhaled corticosteroids if they have a positive response to hyperosmolar challenge with mannitol than if their response is negative.
Detailed description
In patients with chronic obstructive pulmonary disease (COPD), the treatment with inhaled corticosteroids (ICS) is controversial. Preliminary results of our recent pilot study in 30 COPD patients showed for the first time, that ICS response mey be predicted by a bronchoprovocation challenge test with mannitol. However, this finding needs to be proven in a placebo-controlled trial. For this cohort study, 100 corticosteroid-naive, non reversible (FEV1) patients with COPD will be recruited. Spirometry before and after bronchodilation will be measured at study entry and at four weeks run-in (only tiotropium) and at three month of treatment with tiotropium and ICS or placebo. Quality of life (St. George Respiratory Quality of Life Questionnaire) and exacerbation rate of COPD will be assessed. Measurement of exhaled nitric oxide and mannitol challenge will be performed at study entry and at 1 and 4 month. Primary endpoint will be improvement in FEV1 in each group (positive and negative mannitol challenge) after 3 months follow up. Secondary endpoints will be the difference in dose-response-curve in the mannitol challenge, exacerbation rate and change in quality of life after three month follow-up.
Interventions
DRUGBudesonide
After 4 weeks of inhalative therapy with tiotropium (all patients), patient get randomized to receive either inhalative budesonide (1600ug per day or placebo
Sponsors
Cantonal Hosptal, Baselland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* FEV1/FVC \< 70% * FEV1 % predicted \> 60%
Exclusion criteria
* Other major disease * Asthma * Currently taking inhaled corticosteroids * oral corticosteroids in the last 3 month * significant cardiovascular disease * pregnancy/breast feeding * current use of salmeterol or other long acting bronchodilator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Lung Function (FEV1) | 12 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion Who Complete Follow-up Without Developing an Exacerbation | 12 weeks | — |
| Change in Quality of Life | 12 weeks, baseline to 3 months follow-up | St. George Respiratory Questionnaire (SGRQ). Disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores are calculated for three domains: Part I (Symptoms): several scales; Part II (Activity and Impacts): dichotomous (true/false) except last question (4-point Likert scale) Scores range from 0 to 100, with higher scores indicating more limitations. Unit of Measure = Units on a scale A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing. Based on empirical data and interviews with patients, a mean change score of 4 units is associated with slightly efficacious treatment, 8 units for moderately efficacious change and 12 units for very efficacious treatment. The higher the change in units, the better the treatment. |
| Change in logRDR Mannitol | 12 weeks | — |
Countries
Switzerland
Participant flow
Recruitment details
out patient clinic
Pre-assignment details
run-in
Participants by arm
| Arm | Count |
|---|---|
| Budesonide | 31 |
| Placebo | 37 |
| Total | 68 |
Baseline characteristics
| Characteristic | Budesonide | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 23 Participants | 41 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 14 Participants | 27 Participants |
| Age, Continuous | 60 years STANDARD_DEVIATION 16 | 62 years STANDARD_DEVIATION 22 | 61.5 years STANDARD_DEVIATION 20 |
| FEV1/FVC | 63 % STANDARD_DEVIATION 10 | 64 % STANDARD_DEVIATION 10 | 64 % STANDARD_DEVIATION 10 |
| Region of Enrollment Switzerland | 31 participants | 37 participants | 68 participants |
| Sex: Female, Male Female | 12 Participants | 19 Participants | 31 Participants |
| Sex: Female, Male Male | 19 Participants | 18 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 31 | 2 / 37 |
| serious Total, serious adverse events | 1 / 31 | 2 / 37 |
Outcome results
Primary
Change in Lung Function (FEV1)
Time frame: 12 weeks
Population: per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide | Change in Lung Function (FEV1) | 0.05 litres | Standard Deviation 0.01 |
| Placebo | Change in Lung Function (FEV1) | -0.05 litres | Standard Deviation 0.01 |
Secondary
Change in logRDR Mannitol
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide | Change in logRDR Mannitol | 0.12 %/mg | Standard Deviation 0.1 |
| Placebo | Change in logRDR Mannitol | -0.09 %/mg | Standard Deviation 0.01 |
Secondary
Change in Quality of Life
St. George Respiratory Questionnaire (SGRQ). Disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores are calculated for three domains: Part I (Symptoms): several scales; Part II (Activity and Impacts): dichotomous (true/false) except last question (4-point Likert scale) Scores range from 0 to 100, with higher scores indicating more limitations. Unit of Measure = Units on a scale A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing. Based on empirical data and interviews with patients, a mean change score of 4 units is associated with slightly efficacious treatment, 8 units for moderately efficacious change and 12 units for very efficacious treatment. The higher the change in units, the better the treatment.
Time frame: 12 weeks, baseline to 3 months follow-up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide | Change in Quality of Life | 5.1 units | Standard Deviation 5.8 |
| Placebo | Change in Quality of Life | 1.8 units | Standard Deviation 0.3 |
Secondary
The Proportion Who Complete Follow-up Without Developing an Exacerbation
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Budesonide | The Proportion Who Complete Follow-up Without Developing an Exacerbation | 31 number of participants |
| Placebo | The Proportion Who Complete Follow-up Without Developing an Exacerbation | 37 number of participants |