E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute COPD exacerbations with hospitalisation. |
|
E.1.1.1 | Medical condition in easily understood language |
COPD is a chronic lung disease characterized by airflow limitation associated with an abnormal inflammatory response of the lung, aggravated by exacerbations reducing QoL and increasing mortality. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010952 |
E.1.2 | Term | COPD |
E.1.2 | System Organ Class | 100000004855 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010953 |
E.1.2 | Term | COPD exacerbation |
E.1.2 | System Organ Class | 100000004855 |
|
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 |
The first objective is to proof the effectiveness of azithromycin on top of standard therapy in the acute treatment of COPD exacerbations which require hospitalization. |
|
E.2.2 | Secondary objectives of the trial |
A second objective is to proof and improve safety without losing effectiveness by reducing dose and duration of a current everlasting treatment. |
|
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 |
1) BACE Trial: PROactive sub-study The objective is to explore the recovery of physical activity following a positive effect resulting from azitromycine treatment. 2) BACE Trial: FarmEc sub-study The objective is to explore the economic impact of azitromycine in the treatment of acute COPD exacerbations requiring hospitalization. |
|
E.3 | Principal inclusion criteria |
1/ Established diagnosis of COPD by medical doctor (based on clinical history OR pulmonary function test) 2/ Smoking history (≥ 10 pack-years) 3/ Current hospitalization for potential infectious AECOPD treated with standard therapy 4/ History of at least one exacerbation during the last year for which systemic steroids and/or antibiotics were taken 5/ ECG at admission |
|
E.4 | Principal exclusion criteria |
1/ Mechanical or non-invasive ventilation at moment of randomisation (D1) 2/ Long QT interval on ECG (QTc > 450msec for males or > 470msec for females) 3/ History of life-threatening arrhythmias 4/ Myocardial infarction (NSTEMI or STEMI) less than 6 weeks before of start study 5/ Unstable angina pectoris or acute myocardial infarction (NSTEMI or STEMI) at admission 6/ Drugs with high risk for long QT interval and torsade de pointes (amiodarone, flecainide, procainamide, sotalol, droperidol, haldol, citalopram, other macrolides). 7/ Documented uncorrected severe hypokalemia (K+ < 3.0 mmol/L) or hypomagnesemia (Mg2+ <0.5 mmol/L) 8/ Chronic systemic steroids (> 4 mg methylprednisolone /day for ≥ 2 months) 9/ Actual use of macrolides for at least 2 weeks 10/ Allergy to macrolides 11/ Active cancer treatment 12/ Life expectancy < 3 months 13/ Pregnant or breast-feeding women |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is time to treatment failure. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint will be evaluated after 3 months, which is also the day that all study medication will be stopped. |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints of the study will include number of treatment failures, time to new exacerbation, number of exacerbations, total days of hospitalization, total days of intensive care, total days of antibiotics, total dose of systemic steroids but also FEV1 and self-administered symptom or quality of life scores (EQ5D, CCQ, CAT, SSQ5). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoints of the study will be evaluated at discharge, after 3 months and 9 months. |
|
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 | Yes |
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 | Yes |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | 2 |
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 | 19 |
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
|
|
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 | |