E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Obstructive Pulmonary disease |
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E.1.1.1 | Medical condition in easily understood language |
COPD - Chronic Obstructive Pulmonary disease |
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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 |
The primary objective is to study the effect of treatment with a cardio-selective beta-blocker (metoprolol) on major adverse cardiac and pulmonary events i.e. death, exacerbations of COPD and cardiovascular events till 1 year, in patients with COPD and no co-existing cardiovascular disease. |
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E.2.2 | Secondary objectives of the trial |
Our secondary objectives are to study time to all-cause and cause specific death, time to exacerbations of COPD and respectively time to a cardiovascular event within 1 year. Additionally, an extensive health economic analysis will be conducted. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A diagnosis of COPD confirmed by spirometry showing post bronchodilator value of Forced Expiratory Volume in one second (FEV1)//Forced Vital Capacity (FVC) < 70 according to the Global Initiative on Obstructive Pulmonary Disease (GOLD), and with a history of tobacco smoking or occupational/environmental exposure for smoke gas or dust And: - ≥40 years of age. - Sinus rhythm ≥50/min and <120 at inclusion. - Written informed consent. |
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E.4 | Principal exclusion criteria |
- Known hypersensitivity to metoprolol or related derivatives. - AF or other arrhythmias for which beta blockers are indicated according to the investigator discretion. - AV block II or III unless treated with a pacemaker. - Sinus bradycardia (resting heart rate <50/min). - Sick sinus syndrome unless treated with a pacemaker. - Clinical signs of or a previous diagnosis of HF. - Systolic blood pressure <90 mmHg. - Severe bronchial asthma. - Current beta-blocker treatment. - Inability to provide informed consent. - Age below 40 years. - Acute on-going exacerbation of COPD. - Previous randomization in the BRONCHIOLE trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
A composite of death, exacerbations of COPD, (defined as hospitalization with a primary hospital diagnosis with International Classification of Diseases 10th edition discharge codes for COPD [J44.0 or J44.1] or a COPD exacerbation where a course of per oral steroids was prescribed), and cardiovascular events (AMI, angina pectoris, HF and stroke, TIA or cerebral hemorrhage) requiring hospitalization till 1 year. |
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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) |
- death (all-cause and cause-specific) till 1 year - exacerbation of COPD according to the definition above till 1 year - hospitalization for MI or angina pectoris till 1 year - hospitalization for AF or other forms of arrhythmia - hospitalization for stroke, TIA or cerebral hemorrhage - hospitalization for HF till 1 year - Additionally, an extensive health-economic analysis will be conducted
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 20 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |