EUCTR2012‐002742‐20‐CZ.

Study name	Effect of ivabradine versus placebo on cardiac function and on capacity to perform exercise in patients suffering from diastolic heart failure
Methods	Study design: Interventional clinical trial of medicinal product Controlled: yes; Randomised: yes; Open: no; Single‐blind: no; Double‐blind: yes; Parallel group: yes; Cross‐over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Number of treatment arms in the trial: 2 Unit of randomisation: No information Total duration of study: 8 months Intervention time: 8 months Follow‐up: No information Setting: International multicentre trial (Argentina, Australia, Austria, Belgium, Brazil, the Czech Republic, France, Germany, Hungary, Ireland, Italy, Korea, Republic of Netherlands, Poland, Portugal, Russian Federation, Slovenia, Spain, Taiwan, the United Kingdom)
Participants	Type of heart failure: HF‐PEF N = 400 participants Age: > 50 years Gender: Both males and females Inclusion criteria: 1. Male or female patients 2. Aged 50 years or older 3. Symptomatic chronic heart failure of NYHA class II or III for at least 3 months prior to selection 4. In stable clinical condition with regard to CHF symptoms for at least 4 weeks prior to selection 5. Documented sinus rhythm and HR superior or equal to 70 bpm on a resting standard 12‐lead ECG at selection and inclusion 6. Left ventricular ejection fraction superior or equal to 45% and E/e’ > 13 (E = early diastolic mitral flow velocity; e’ = mean of mitral annular lateral and septal proto diastolic velocities) or e’ lateral < 10 cm/s and e’ septal < 8 cm/s or LAVI > 34 mL/m2 at selection 7. Documented NT‐pro‐BNP >= 220 pg/mL or BNP >= 80 pg/mL at selection Exclusion criteria: 1. Recent (less than 3 months) myocardial infarction or coronary revascularisation 2. Scheduled coronary revascularisation 3. Severe aortic or mitral stenosis, or severe aortic regurgitation, or severe primary mitral regurgitation 4. Scheduled surgery for valvular heart disease 5. Congenital heart disease 6. Previous cardiac transplantation or on list for cardiac transplantation 7. Documented permanent atrial fibrillation or other cardiac arrhythmia that interferes with the sinus node function, or recent hospitalisation for atrial fibrillation or other cardiac arrhythmia that interferes with the sinus node function within the last 3 months 8. Patients able to walk more than 450 metres within 6 minutes during the selection and the inclusion visits 9. Previous treatment with ivabradine within the last 6 months before selection, or current treatment with ivabradine 10. Previous mitral valvular surgery or intervention
Interventions	Intervention: Ivabradine 2.5 mg to 5 mg to 7.5 mg Comparison: Placebo Concomitant medications: No information Excluded medications: No information
Outcomes	Outcomes measured in the study: Primary outcome: [up to M008] Co‐primary endpoints based on echocardiography (E/e') Neuroendocrine activation (NT‐pro‐BNP) 6‐minute walk test Secondary outcome: [All over the study] Efficacy and safety endpoints
Starting date	7 Mai 2013 (not recruiting)
Contact information	Clinical Studies Department Institut de Recherches Internationales Servier 50, rue Carnot 92284 Suresnes Cedex France Phone: +33155 72 43 66 Email: clinicaltrials@servier.com
Notes	Primary sponsor: Institut de Recherches Internationales Servier Ethics status: No information