E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary Disease (COPD) patients |
COPD patiënten |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effectiveness of triple therapy (ICS/LABA/LAMA) on the change in health status, measured with the Clinical COPD Questionnaire (CCQ), in symptomatic ICS-naive COPD patients with characteristics of asthma according to GOLD 2019 and blood eosinophil counts of ≥100 cells per µL compared to treatment with dual therapy (LABA/LAMA), within a primary care population. Effectiveness is regarded as the difference in the proportion of patients with a minimal clinically improvement on health status (CCQ improvement ≥0.4) between the study groups. |
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E.2.2 | Secondary objectives of the trial |
- Identify patient and disease characteristics predictive for triple therapy effectiveness. - To compare the number of moderate and severe exacerbations before and during the study between the study groups. - To compare the proportion of net responders minus negative responders between the study groups. - To compare the proportion of patients with clinically relevant improvement on either one or both, the CCQ or the ACQ. - To compare the properties of the CCQ and the COPD Assessment Test (CAT). - To compare the difference in lung function measures, Eos and FeNO between the study groups. - To describe patient reported side effects using the ICQ-S. - To collect health resource utilisation data and investigate the difference in health resource use and costs between the study groups. - To investigate the difference in the pneumonia incidence between the study groups. - To compare the properties of the CCQ and the COPD Assessment Test (CAT) over the study period. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
- To investigate the differences in genome-wide expression of mRNA, MiRNA and methylation status in epithelial cells derived from nasal brushings between the study groups. |
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E.3 | Principal inclusion criteria |
- Physician diagnosis of COPD (documented obstruction or obstruction measured at the first study visit) - Age 40 years and older - Symptomatic (defined as Clinical COPD Questionnaire score ≥ 1) - ICS-naive (last 12 months no ICS containing treatment) - Usage of a long-acting bronchodilator; either usage of a single LABA or LAMA, usage of a single LABA and a single LAMA, or a usage of a single LABA/LAMA inhaler. Patients are allowed to use short-acting bronchodilator. - Blood eosinophils ≥100 cells per µL and one or more characteristics of asthma according to GOLD 2019. |
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E.4 | Principal exclusion criteria |
- Chronic oral corticosteroid, use more than 60 days in the last 3 months - Recent exacerbation (last 6 weeks before inclusion) - Life expectancy of less than 2 years - Allergy to intervention formulation - Inability to understand Dutch or Greek - Any other condition which, at the GPs and/or investigator’s discretion, is believed to present a safety risk or may impact the study results - Patients participating in another ongoing clinical trial that in the investigator’s opinion influences the current study (e.g. another randomized controlled trial) - Inability to understand and sign the written consent form.
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E.5 End points |
E.5.1 | Primary end point(s) |
To investigate the effectiveness of triple therapy (ICS/LABA/LAMA) on the change in health status, measured with the Clinical COPD Questionnaire (CCQ), in symptomatic ICS-naive COPD patients with characteristics of asthma according to GOLD 2019 (Table 1) or blood eosinophil counts of ≥100 cells per µL compared to treatment with dual therapy (LABA/LAMA), within a primary care population. Effectiveness is regarded as difference in the proportion of patients a with minimal clinically improvement on health status (CCQ improvement ≥0.4) between the study groups. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- To identify patient and disease characteristics that are predictive for triple therapy effectiveness. Effectiveness is defined as improvement in CCQ of ≥0.4 from baseline to follow-up. - To compare the number of moderate and severe exacerbations before (6 months) and during the study (6 months) between the study groups. - To compare the proportion of net responders (positive responders (≥0.4 improvement on the CCQ) minus negative responders (≤0.4 decline on the CCQ)) between the study groups. - To compare the proportion of patients with clinically relevant improvement on either one or both, the CCQ (≥0.4) or the ACQ (≥0.5). - To compare the properties of the CCQ and the COPD Assessment Test (CAT) over the study period. - To compare the difference in lung function measures, Eos and FeNO between the study groups. - To describe patient reported side effects using the Inhaled Corticosteroids side-effect Questionnaire Short Form (ICQ-S). - To collect health resource utilisation data (e.g. exacerbations, hospitalisations) and investigate the difference in health resource use and costs between the study groups. - To investigate the differences in genome-wide expression of mRNA, MiRNA and methylation status in epithelial cells derived from nasal brushings between the study groups. - To investigate the difference in the pneumonia incidence between the study groups; |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For each patient the duration of the study is 26 weeks. The data will be collected between December 2019 and March 2026. In the subsequent months the data will be analyzed, and a manuscript will be written. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS. Early termination may occur at the discretion of the investigators/sponsor(Sp) for any reason that is believed to present a safety risk. If the investigator/Sp terminates the trial without prior-agreement of the subsidising party, the investigator/Sp should instantly inform the subsidising party and provide them with a detailed written explanation for the termination of the trial. If the subsidising party terminates the trial, the subsiding party should instantly inform the investigator/Sp |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |