COPDPhase 4NCT02546349
Exhaled NO Based Treatment of Chronic Obstructive Pulmonary Disease (COPD), ICS/LABA Versus LAMA
A Phase 4 study testing fluticasone/salmeterol, tiotropium in people with COPD, run by Taipei Veterans General Hospital, Taiwan at 1 site in Taiwan.
Trial summary
It is recognized that eosinophilic airway inflammation is more likely respond to steroid treatment. However, in real-world practice, it is difficult to routinely assess airway inflammation using sputum induction because of technical and facility requirement. Read more about this study
- Who is it for?
- Ages 40 to 90 years
- Conditions the study is for
- COPD
- What is being tested?
- fluticasone/salmeterol, tiotropium
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 143 participants
- Where
- 1 siteTaiwan
- Study dates
- Jul 2014to Jan 2016
- 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 40 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female outpatients aged from 40 to 90 years
- Current or ex-smoker, with smoking history ≧ 20 pack- years
- Newly diagnosed or untreated (at least 3 months) COPD patients (forced expiratory volume in first second (FEV1)/forced vital capacity (FVC) < 70%) with post-bronchodilator FEV1 < 80 % predicted value.
Who cannot join
- Concurrent allergic rhinitis, eczema, and asthma.
- Clinically overt bronchiectasis, lung cancer, active tuberculosis, or other known specific pulmonary disease.
- A chest X-ray indicating diagnosis other than COPD that might interfere with the study.
- Major disease abnormalities are uncontrolled on therapy.
- Alcohol or medication abuse.
- Patients had lower respiratory tract infections or received systemic steroid in the 4 weeks prior to the commencement of study.
- Women with childbearing potential during the period of trial.
- Unable or unwilling to comply with all protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Treatment Effect of Inhaled Corticosteroid and Long-acting beta2 Agonist Combination Versus Long-acting Anti-cholinergic Agent on Stratified COPD Patients Based on the Levels of Exhaled Nitric Oxide
It is recognized that eosinophilic airway inflammation is more likely respond to steroid treatment. However, in real-world practice, it is difficult to routinely assess airway inflammation using sputum induction because of technical and facility requirement. COPD (chronic obstructive pulmonary disease) is a heterogeneous disease and it remains a great challenge to identify patients who have eosinophilic airway inflammation and respond to steroid treatment well. A recent study demonstrated elevated plasma D-dimer was associated with acute inflammation and a significant predictor of pulmonary embolism in COPD exacerbated patients. D-dimer may potentially act as a marker of inflammation and a predictor of cardiovascular event in COPD patients. The investigators preliminary study demonstrated that exhaled nitric oxide (eNO) > 23.5 ppb is a good surrogate marker to predict eosinophilic airway inflammation in COPD patients who were newly diagnosed or untreated for at least 3 months. There were significant correlations among sputum eosinophils, eNO and serum total immunoglobulin E (IgE). Particularly, eNO predicted sputum eosinophilia (> 3%) in COPD at a sensitivity and specificity of 62% and 71% respectively. Herein, the investigators test the hypothesis that eNO may act as a biomarker to determine treatment option for COPD.
Read the detailed description
Eligible COPD patients (newly diagnosed or untreated for at least 3 months) will be enrolled at out-patient clinic after consenting by participants. Upon enrollment, exhaled NO (eNO) will be measured and patients will be categorized into 2 groups according to eNO levels: either high exhaled NO (greater than or equal to 23.5 ppb) or low eNO (< 23.5 ppb) group. In each group, patients will be randomized to receive either 2 inhalations of fluticasone/salmeterol 250/25 mcg/ pudd twice daily or 2 inhalations of tiotropium 2.5 mcg/inhalation for 12 weeks and followed at scheduled visits. Testing outcome measures include eNO, lung function, different count and mediators in induced sputum, and which will be tested as the following timings: before (baseline, week 0), and after treatment (week 4 and week 12). Rescue medication and drug compliance will be record.
- Conditions
- COPD
- Being tested
- fluticasone/salmeterol, tiotropium
- Keywords
- chronic obstructive pulmonary disease, airway inflammation, eosinophilic airway inflammation, exhaled nitric oxide
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fluticasone/salmeterol, tiotropiumDrug
Also called seretide evohaler 250, spiriva respimat
In group (either high or low eNO), patients will be randomized to receive either 2 puffs of fluticasone/salmeterol 250/25 mcg/puff twice daily or 2 inhalations of tiotropium respimat 2.5 mcg/inhalation once daily for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| high eNO: ICS/LABA | Experimental | patients with eNO >=23.5 ppb, receive inhaled corticosteroid (ICS)/long-acting beta2 agonist (ICS/LABA) of fluticasone/salmeterol 250/25 mcg/puff, 2 puffs bid. Receives: Drug: fluticasone/salmeterol, tiotropium |
| high eNO: LAMA | Active comparator | patients with eNO >=23.5 ppb, receive long acting muscarinic antagonist (LAMA) of tiotropium 2 inhalations 2.5 mcg/inhalation, once daily Receives: Drug: fluticasone/salmeterol, tiotropium |
| Low eNO: ICS/LABA | Experimental | patients with eNO < 23.5 ppb, receive fluticasone/salmeterol 250/25 mcg/puff, 2 puffs bid Receives: Drug: fluticasone/salmeterol, tiotropium |
| Low eNO: LAMA | Active comparator | patients with eNO < 23.5 ppb, receive tiotropium 2 inhalations 2.5 mcg/inhalation, once daily Receives: Drug: fluticasone/salmeterol, tiotropium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes of eNO level
Measured: Changes of eNO level (ppb) from baseline at 12 weeks
Secondary outcomes (7)
Changes of lung function parameters (FEV1, FVC)
Measured: Changes of lung function parameters (FEV1, FVC) from baseline at 12 weeks
Changes of serum level of IgE
Measured: Changes of serum level of IgE (IU/ml) from baseline at 12 weeks
Changes of serum level of matrix metalloproteinase (MMP)-9
Measured: Changes of serum level of MMP-9 (ng/ml) from baseline at 12 weeks
Changes of serum level of D-dimer
Measured: Changes of serum level of D-dimer (ug/ml) from baseline at 12 weeks
Changes of scales of life quality questionnaire
COPD assessment test (CAT)
Measured: Changes of scales of life quality questionnaire from baseline at 12 weeks
Changes of proportion of cell counts in induced sputum
Measured: Changes of proportion of cell counts in induced sputum from baseline at 12 weeks
Changes of MMP-9 level in induced sputum
Measured: Changes of MMP-9 levle (ug/ml) in induced sputum from baseline at 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2015 (estimated)
- Study startJul 2014
- Primary completionDec 2015 (estimated)
- Study completionJan 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COPDStudies of the same condition, open and under way.
- More trials run by Taipei Veterans General Hospital, TaiwanThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 143 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Taipei Veterans General Hospital, Taiwan
- Sponsor type
- Other government
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Diahn-Warng S Perng, PhD, Study chair, Taipei Veterans General Hospital, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02546349
- Sponsor's protocol ID
- 140420
- Status last verified
- Sep 2015
- First submitted
- 25 Feb 2015
- Last updated
- 10 Sep 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Su KC, Ko HK, Hsiao YH, Chou KT, Chen YW, Yu WK, Pan SW, Feng JY, Perng DW. Fractional Exhaled Nitric Oxide Guided-Therapy in Chronic Obstructive Pulmonary Disease: A Stratified, Randomized, Controlled Trial. Arch Bronconeumol. 2022 Aug;58(8):601-610. doi: 10.1016/j.arbres.2021.11.013. Epub 2021 Dec 18. English, Spanish.
PubMed 35312525
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Treatment Effect of Inhaled Corticosteroid and Long-acting beta2 Agonist Combination Versus Long-acting Anti-cholinergic Agent on Stratified COPD Patients Based on the Levels of Exhaled Nitric Oxide
- ClinicalTrials.gov ID
- NCT02546349
- Acronym / sponsor ID
- 140420
- Conditions
- COPD
- Keywords
- chronic obstructive pulmonary disease, airway inflammation, eosinophilic airway inflammation, exhaled nitric oxide
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 143 participants (estimated)
- Lead sponsor
- Taipei Veterans General Hospital, TaiwanOther government
- Collaborators
- GlaxoSmithKline
- Study start
- Jul 2014
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Jan 2016 (estimated)
- First posted
- 10 Sep 2015 (estimated)
- 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.
It is recognized that eosinophilic airway inflammation is more likely respond to steroid treatment. However, in real-world practice, it is difficult to routinely assess airway inflammation using sputum induction because of technical and facility requirement. COPD (chronic obstructive pulmonary disease) is a heterogeneous disease and it remains a great challenge to identify patients who have eosinophilic airway inflammation and respond to steroid treatment well. A recent study demonstrated elevated plasma D-dimer was associated with acute inflammation and a significant predictor of pulmonary embolism in COPD exacerbated patients. D-dimer may potentially act as a marker of inflammation and a predictor of cardiovascular event in COPD patients. The investigators preliminary study demonstrated that exhaled nitric oxide (eNO) > 23.5 ppb is a good surrogate marker to predict eosinophilic airway inflammation in COPD patients who were newly diagnosed or untreated for at least 3 months. There were significant correlations among sputum eosinophils, eNO and serum total immunoglobulin E (IgE). Particularly, eNO predicted sputum eosinophilia (> 3%) in COPD at a sensitivity and specificity of 62% and 71% respectively. Herein, the investigators test the hypothesis that eNO may act as a biomarker to determine treatment option for COPD.
Detailed description
Eligible COPD patients (newly diagnosed or untreated for at least 3 months) will be enrolled at out-patient clinic after consenting by participants. Upon enrollment, exhaled NO (eNO) will be measured and patients will be categorized into 2 groups according to eNO levels: either high exhaled NO (greater than or equal to 23.5 ppb) or low eNO (< 23.5 ppb) group. In each group, patients will be randomized to receive either 2 inhalations of fluticasone/salmeterol 250/25 mcg/ pudd twice daily or 2 inhalations of tiotropium 2.5 mcg/inhalation for 12 weeks and followed at scheduled visits. Testing outcome measures include eNO, lung function, different count and mediators in induced sputum, and which will be tested as the following timings: before (baseline, week 0), and after treatment (week 4 and week 12). Rescue medication and drug compliance will be record.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| high eNO: ICS/LABA | Experimental | Drug: fluticasone/salmeterol, tiotropiumpatients with eNO >=23.5 ppb, receive inhaled corticosteroid (ICS)/long-acting beta2 agonist (ICS/LABA) of fluticasone/salmeterol 250/25 mcg/puff, 2 puffs bid. |
| high eNO: LAMA | Active comparator | Drug: fluticasone/salmeterol, tiotropiumpatients with eNO >=23.5 ppb, receive long acting muscarinic antagonist (LAMA) of tiotropium 2 inhalations 2.5 mcg/inhalation, once daily |
| Low eNO: ICS/LABA | Experimental | Drug: fluticasone/salmeterol, tiotropiumpatients with eNO < 23.5 ppb, receive fluticasone/salmeterol 250/25 mcg/puff, 2 puffs bid |
| Low eNO: LAMA | Active comparator | Drug: fluticasone/salmeterol, tiotropiumpatients with eNO < 23.5 ppb, receive tiotropium 2 inhalations 2.5 mcg/inhalation, once daily |
Who may qualify
- Ages
- 40 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male or female outpatients aged from 40 to 90 years
- Current or ex-smoker, with smoking history ≧ 20 pack- years
- Newly diagnosed or untreated (at least 3 months) COPD patients (forced expiratory volume in first second (FEV1)/forced vital capacity (FVC) < 70%) with post-bronchodilator FEV1 < 80 % predicted value.
Key exclusion criteria (8 listed)
- Concurrent allergic rhinitis, eczema, and asthma.
- Clinically overt bronchiectasis, lung cancer, active tuberculosis, or other known specific pulmonary disease.
- A chest X-ray indicating diagnosis other than COPD that might interfere with the study.
- Major disease abnormalities are uncontrolled on therapy.
- Alcohol or medication abuse.
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 |
|---|---|---|
| fluticasone/salmeterol, tiotropiumAlso: seretide evohaler 250, spiriva respimatIn group (either high or low eNO), patients will be randomized to receive either 2 puffs of fluticasone/salmeterol 250/25 mcg/puff twice daily or 2 inhalations of tiotropium respimat 2.5 mcg/inhalation once daily for 12 weeks. | Drug | Low eNO: ICS/LABA, Low eNO: LAMA, high eNO: ICS/LABA, high eNO: LAMA |
Primary outcome
Changes of eNO level
Time frame: Changes of eNO level (ppb) from baseline at 12 weeks
7 secondary outcomes
Changes of lung function parameters (FEV1, FVC)
Time frame: Changes of lung function parameters (FEV1, FVC) from baseline at 12 weeks
Changes of serum level of IgE
Time frame: Changes of serum level of IgE (IU/ml) from baseline at 12 weeks
Changes of serum level of matrix metalloproteinase (MMP)-9
Time frame: Changes of serum level of MMP-9 (ng/ml) from baseline at 12 weeks
Changes of serum level of D-dimer
Time frame: Changes of serum level of D-dimer (ug/ml) from baseline at 12 weeks
Changes of scales of life quality questionnaire
Time frame: Changes of scales of life quality questionnaire from baseline at 12 weeks
Changes of proportion of cell counts in induced sputum
Time frame: Changes of proportion of cell counts in induced sputum from baseline at 12 weeks
Changes of MMP-9 level in induced sputum
Time frame: Changes of MMP-9 levle (ug/ml) in induced sputum from baseline at 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2015.
- Derived from this study: PubMed 35312525Su KC, Ko HK, Hsiao YH, Chou KT, Chen YW, Yu WK, Pan SW, Feng JY, Perng DW. Fractional Exhaled Nitric Oxide Guided-Therapy in Chronic Obstructive Pulmonary Disease: A Stratified, Randomized, Controlled Trial. Arch Bronconeumol. 2022 Aug;58(8):601-610. doi: 10.1016/j.arbres.2021.11.013. Epub 2021 Dec 18. English, Spanish.
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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.
Diahn-Warng S Perng, PhD study chair
Taipei Veterans General Hospital, Taiwan
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 fluticasone/salmeterol, tiotropium in people with COPD, run by Taipei Veterans General Hospital, Taiwan at 1 site in Taiwan.
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 8 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: status not confirmed, as of the sponsor's last update on 10 Sep 2015. 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 Taiwan. 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?
Results are not available in the source record.
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?
Changes of eNO level (time frame: Changes of eNO level (ppb) from baseline at 12 weeks). 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 NCT02546349, which also lists 1 linked publication.
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 10 Sep 2015.