E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Clinicaltrial on eosinophil-guided time-updated person-specific reduction of inhaled corticosteroid therapy and prophylactic azithromycin therapy in patients with severe or very severe chronic obstructive pulmonary disease (COPD) |
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E.1.1.1 | Medical condition in easily understood language |
Individial adjustet inhaled corticosteroid therapy and prophylactic azithromycin treatment in chronic obstructive pulmonary disease. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Parasitic Diseases [C03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
E.1.2 | System Organ Class | 100000004855 |
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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 |
ICS: • Whether a strategy of eosinophil-guided administration of inhaled corticosteroids in COPD patients (GOLD risk class C/D and/or FEV1 < 30%) can lead to non-inferior treatment responses to triple therapy (ICS/LABA/LAMA). • Whether side effects and exposure to ICS can be reduced with the eosinophil-guided administration of inhaled corticosteroids.
Azithromycin: • Whether the use of prophylactic low dose Azithromycin in COPD patients (GOLD risk class C/D and/or FEV1 < 30%) can improve “time alive and out of hospital” while reducing moderate and severe exacerbations.
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E.2.2 | Secondary objectives of the trial |
ICS: • Whether a strategy of eosinophil-guided administration of inhaled corticosteroids in COPD patients (GOLD risk class C/D and/or FEV1 < 30%) leads to a change in the respiratory microbiota abundance and diversity in comparison to continuous triple therapy (ICS/LABA/LAMA).
Azithromycin: • Whether prophylactic low dose Azithromycin in COPD patients (GOLD risk class C/D and/or FEV1 < 30%) leads to changes in the respiratory microbiota abundance and diversity.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• COPD (verified by a specialist in respiratory medicine + spirometry). • GOLD risk class C/D anytime within the last 2 years (corresponding to 2 ≥ AECOPD and/or ≥1 AECOPD leading to hospitalization during a 12 months period within the last 2 years) and/or FEV1<30%. • Must receive at least during last 4 weeks: LAMA, LABA and ICS. • Informed consent.
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E.4 | Principal exclusion criteria |
• Known asthma • Male <40 years • Female <40 years, if non-menopausal (had menstruation within the last 12 months) conditioned by a negative urine HCG test • Severe mental illness which considerably complicates co-operation. • Language problems that considerably complicate co-operation. • Current treatment with systemic corticosteroids corresponding to > 5 mg prednisolone per day. • Systemic antibiotic treatment or systemic corticosteroid treatment within 14 days (also prophylactic Azithromycin). • Contra-indication to treat with Azithromycin (as listed by the producer). • Non-bacterial exacerbation per investigator judgement in the last 3 months.
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E.5 End points |
E.5.1 | Primary end point(s) |
ICS and Azithromycin:
• “Days alive and out of hospital within 365 days after recruitment” (continuous data: analysis with T-test) • Number of hospitalization-requiring exacerbations and/or death within 365 days (continuous data: analysis with chi squared test)
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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) |
Secondary end points ICS and Azithromycin: • Death or “uncontrolled AECOPD tendency” within 365 days. • Number of moderate/severe exacerbation within 365 days • Cumulative dose of inhaled corticosteroids within 365 days • Cumulative dose of systemic corticosteroids within 365 days • Change in lung function (ΔFEV1) from baseline to 365 days Explanatory end points ICS: • Change in blood eosinophils from baseline to 365 days (eosinophilic trajectories) • New diagnosis of diabetes mellitus within 365 days • Change in HbA1c from baseline to 365 days • Antibiotic-requiring infections within 365 days
ICS and Azithromycin: • Difference in respiratory microbiota abundance and diversity at 6 months between treatment arms • Change in COPD-related quality of life (Based on COPD Assessment Test - CAT) from baseline to 365 days • Number who progress to MRC -dyspnea score from < 3 to ≥3 anytime during follow-up (assessed every 3 months). • Number of admission requiring NIV treatment or admissions to intensive care within 365 days • Mortality within 365 days
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At baseline and 12 months, except blood samples and MRC every 3 month (baseline, 3, 6, 9 and 12 months) |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
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 | No |
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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The trial will end at last follow up 12 months after the last patient is included |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |