E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with diastolic dysfunction |
|
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 |
This study is designed to assess the long-term effects of the administration of nebivolol, compared to placebo, on the clinical symptoms, exercise capacity and parameters of left ventricular function in the patients with diastolic heart failure. |
|
E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Subjects is aged ≥40 years - Symptoms of heart failure; a documented history of heart failure - A left ventricular ejection fraction ≥ 45% assessed by echocardiography, radionuclide ventriculography or magnetic resonance (MRI) - NYHA functional class II or III - The subject has given written informed consent for participation in the study. The subject is able and willing to visit the hospital for the planned study visits - Any diastolic abnormality well documented on echocardiography following the diagnostic criteria for diastolic heart failure published by the 'European Study Group on Diastolic Heart Failure'
|
|
E.4 | Principal exclusion criteria |
- The subject is unable to perform a 6 minutes walking test - Planned invasive cardiac procedures carried out during the study e.g. 6 months after randomisation - The subject had recently (< 3 months) unstable angina, acute myocardial infarction or stroke treated with a beta-blocker - The subject has exercise induced myocardial ischemia as a main cause of exercise impairment as shown by limiting symptoms (angina) or by the previous exams (exercise test, exercise echocardiography or myocardial scintigraphy) - The subject has concomitant diseases (COPD (FEV1 < 50%), peripheral arterial disease, orthopedic diseases) as the main cause of exercise impairment - Presence of major contraindications to beta-blocker therapy, such as severe sinus bradycardia (<50 beats/min), atrio-ventricular block, bronchial asthma sensitive to beta-agonist agents, unstable heart failure, sick sinus syndrome including sino-atrial block, untreated pheochromocytoma, metabolic acidosis, hypotension and severe peripheral vascular disturbances. - The subject is treated with verapamil or diltiazem - The subject has a systolic blood pressure < 100 mmHg - The subject is pregnant, or breast feeding, or of childbearing potential without using adequate contraception. Adequate methods of contraception are: hormonal contraception-oral, patch or progestagens injection-, vaginal ring, Intra-uterine device, all methods, which demonstrate a failure rate <1 %). - The subject has a history of alcohol or other illicit drug abuse - The subject suffers from any other medical condition that may exclude the patient for safety reasons or interfere with the objective of the study according to the investigator’s judgment - The subject is expected to have a poor compliance to the study drug therapy - The subject is participating in any other clinical trial with an investigational product, or the subject is scheduled to receive any such product during the study or in the 4 weeks following the study - A left ventricular ejection fraction < 45% assessed by any one of the methods use during the study e.g. echocardiography, radionuclide ventriculography or magnetic resonance imaging (MRI) - Uncontrolled arterial hypertension defined as >160/95 mmHg. - Systolic cardiac insufficiency for which the treatment with beta blockers is indicated. - Any significant alteration of the hepatic function defined as a 2 fold increase of transaminases. - Hypersensitivity to NebiletÒ or its excipients
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The distance as recorded in the 6 minutes walking test |
|
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 | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
|
The trial will end with the last visit of the last subject. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |