The primary objective of this study in patients with symptomatic chronic Heart Failure and Preserved left ventricular Ejection Fraction (HF-PEF) is to determine whether ivabradine compared to placebo could improve the diastolic function, the…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoints of the study are the following:
the ratio E/e*, measured on echocardiography,
the 6-minute walk test,
NT-proBNP plasma level.
Secondary outcome
The secondary objectives are:
-to evaluate the effects of ivabradine compared to placebo on:
• cardiac function and structural parameters,
• quality of life,
• NYHA classification,
• other biomarkers (including optional microRNA),
-and to evaluate the safety and tolerance profile of ivabradine compared to
placebo.
Background summary
The prevalence of Heart Failure (HF) is about 1-2% of the population in
developed countries increasing to >= 10% in 70 year-old-people or more. Heart
Failure with Preserved Ejection Fraction (HF-PEF) is present in half of the
patients with HF. Predisposing conditions for HF-PEF are older age, female
gender, diabetes, obesity, arterial hypertension and LV hypertrophy. However,
the prevalence of HF-PEF is rising due to the aging of population, and no
treatment has yet been shown to be effective in reducing morbidity and
mortality in this population.
Recently, the SHIFT study has shown that reducing HR with ivabradine in
patients with symptomatic systolic HF was associated with a significant
improvement of cardiovascular outcomes: the risk for cardiovascular death or
hospitalisation for worsening heart failure was reduced by 18% with ivabradine
versus placebo.
The hypothesis of a beneficial effect of a specific HR-lowering drug such as
ivabradine in patients with HF-PEF is based on the fact that an elevated HR
decreases the diastolic filling time, increase myocardial oxygen consumption
and impair coronary perfusion which may be problematic for patients with HF. A
specific HR-lowering agent, without any decrease in the myocardial
contractility and without conduction disturbance seems potentially of interest
and will be further evaluated in this 'proof of concept' study.
Study objective
The primary objective of this study in patients with symptomatic chronic Heart
Failure and Preserved left ventricular Ejection Fraction (HF-PEF) is to
determine whether ivabradine compared to placebo could improve the diastolic
function, the exercise capacity, and the neuroendocrine activation, over an
8-month treatment period.
Study design
This is a phase II, multicentre, international, randomised, with therapeutic
benefit, double-blind, placebo-controlled, two-balanced parallel arm study,of a
duration of approximative 8.5 months. There are 7 study visits planned per
patient.
Intervention
Patients will receive ivabradine or placebo in addition to their usual
cardiovascular treatment. Ivabradine and placebo will be administered orally
b.i.d. during meals. The study medication dosis can be adapted by the
investigator, at any time during the study visits or between visits, depending
on the heart rate at rest (ECG) or if signs or symptoms of bradycardia are
reported.
Study burden and risks
The safety and tolerance profile of ivabradine is good (see SmPC Procoralan).
The most common adverse events with ivabradine are visual symptoms (phosphenes)
and bradycardia. Other possible side effects are abnormal sensation of
heartbeat, irregular rapid contraction of the heart, uncontrolled
bloodpressure, headache, dizziness and blurred vision. Visual symptoms are
generally mild, well tolerated and transitory. Bradycardia is a dose dependent
effect of ivabradine, which occurs mainly at the beginning of therapy. The
dosis of the study medication can be reduced following heart rate during the
study at any time, by the investigator.Patients with a heart rate below 50 bpm,
will have to stop study treatment.
Internationalelaan 57
Brussel 1070
BE
Internationalelaan 57
Brussel 1070
BE
Listed location countries
Age
Inclusion criteria
- Male or female patients,;- Aged 50 years or older,;- Symptomatic Chronic Heart Failure of New York Heart Association (NYHA) class II or III for at least 3 months prior to selection,;- In stable clinical condition with regards to CHF symptoms for at least 4 weeks prior to selection,;- Documented sinus rhythm and HR superior or equal to 70 bpm on a resting standard 12-lead ECG at selection and inclusion,;- Left Ventricular Ejection Fraction superior or equal to 50% 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,;- Documented NT-proBNP >= ; 300 pg/mL or BNP >= ; 100 pg/mL at selection.
-Ability to perform the 6' walk test
Exclusion criteria
- Recent (less than 3 months) myocardial infarction or coronary revascularisation,;- Scheduled coronary revascularisation,;- Severe aortic or mitral stenosis, or severe aortic regurgitation, or severe primary mitral regurgitation,;- Scheduled surgery for valvular heart disease;- Congenital heart disease,;- Previous cardiac transplantation or on list for cardiac transplantation,;- Documented permanent atrial fibrillation or other cardiac arrhythmia that interfere with the sinus node function, or recent hospitalization for atrial fibrillation or other cardiac arrhythmia that interfere with the sinus node function within the last 3 months, ;- Patients able to walk more than 450 meters within 6 minutes during the selection and the inclusion visits,;- Previous or current treatment with ivabradine.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | https://www.clinicaltrialsregister.eu |
| EudraCT | EUCTR2012-002742-20-NL |
| CCMO | NL43625.042.13 |