A phase II trial to study neladenoson bialanate over 20 weeks in patients with chronic heart failure with reduced ejection fractio
- Conditions
- chronic heart failure with reduced ejection fraction (LVEF equal or below 35%)Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]MedDRA version: 20.0Level: LLTClassification code 10066498Term: Cardiac failure chronic aggravatedSystem Organ Class: 100000004849
- Registration Number
- EUCTR2016-003839-38-IT
- Lead Sponsor
- BAYER AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 427
1. Men or women aged 18 years and older
2. Diagnosis of chronic heart failure (CHF), NYHA class II-IV, LVEF = 35% assessed by any imaging modality (e.g. echocardiography, cardiac magnetic resonance [CMR], cine levocardiography) within 6 months prior to run-in: if several values are available the last assessment of EF should be = 35%.
3. One of the following (or both),
a) Worsening CHF requiring hospitalization or an unscheduled outpatient visit in the last 3 months, both requiring initiation or intensification of heart failure therapy and with either:
o BNP = 100 pg/mL or NT-proBNP =400 pg/mL (sinus rhythm) or
o BNP = 300 pg/mL or NT-proBNP =1200 pg/mL (atrial fibrillation)
AND/OR
b) at any time in the past 4 weeks one of:
o BNP = 300 pg/mL or NT-proBNP = 1200 pg/mL (sinus rhythm)
o BNP = 600 pg/mL or NT-proBNP = 2400 pg/mL (atrial fibrillation)
For patients on treatment with angiotensin receptor-neprilysin inhibitors (ARNIs), e.g. Entresto only NT-proBNP values can be used to assess eligibility.
4. Written informed consent before any study-specific procedure
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 96
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 288
1. Acute de-novo heart failure
2. Requirement of any of the following 48 hours prior to randomization:
IV vasodilating drugs (e.g. nitrates, nitroprusside)
- IV natriuretic peptides (e.g. nesiritide, carperitide) - IV positive
inotropic agents - IV diuretics - IV antibiotics - Mechanical support (e.g.
intra-aortic balloon pump, endotracheal intubation, mechanical
ventilation, or any ventricular assist device)
3. Any cause of chronic heart failure other than ischemic cardiomyopathy
and idiopathic dilated cardiomyopathy
4. Known clinically significant persistent coronary ischemia based on
medical history, preexisting or current exercise testing
5. Occurrence of any of the following within 3 months prior to
randomization:
o Myocardial infarction
o Hospitalization for unstable angina
o Stroke or TIA
o Coronary artery bypass graft (CABG)
o Percutaneous coronary intervention (PCI)
o Implantation of a cardiac resynchronization therapy device (CRTD)
o Carotid angioplasty
6. PCI, CABG or implantation of a CRTD planned between randomization
and end of study
7. Sustained* systolic blood pressure = 90 mmHg and / or signs and
symptoms of hypotension prior to randomization
8. Sustained* systolic blood pressure = 160 mmHg
9. Sustained* bradycardia with heart rate < 50 beats/minute or
tachycardia with heart rate > 100 beats/minute prior to randomization
10. Known clinically relevant ventricular arrhythmias (sustained
ventricular tachycardia, ventricular flutter or fibrillation) within 3
months prior to consent based on either medical history or ICD-testing
results (if applicable)
11. Clinically relevant permanent or intermittent AV-block > grade II in
patients without a permanent pacemaker or ICD / CRT device
12. Severe valvular disease with indicated or planned valve repair /
replacement
13. Listing for heart transplantation and / or anticipated implantation of
a ventricular assist device14. Severe pulmonary disease with any of the following:
o Requirement of continuous (home) oxygen or
o History of COPD = GOLD III or
o Use of systemic corticosteroids
15. Asthma bronchiale with any of the following:
o Symptoms not well-controlled within the past 6 months or
o Ever intubated or in an intensive care unit for asthma
16. Anemia with hemoglobin < 10 g/dL within 3 months prior to
randomization. If several values are available the latest result should be
used.
17. Body Mass index (BMI) > 40 kg/m2 at randomization or a history of
poor quality LVEF measurement by echocardiography
18. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 calculated by Modification of Diet in Renal Disease (MDRD) formula within 3 months prior to randomization. If several values are available
the latest result should be used.
19. Hepatic insufficiency classified as Child-Pugh B or C, or any of thefollowing:
o Primary biliary cirrhosis (PBC)
o Primary sclerosing cholangitis
o PBC-autoimmune hepatitis overlap syndrome20. Concomitant use of any of the following therapy that cannot be
discontinued:
o Moderate or strong CYP3A4 inhibitors (Of note: grapefruit is also a
strong CYP3A4 inhibitor.)
o CYP3A4 inducers
o Strong CYP2C8 inhibitors (Of note: clopidogrel is a strong CYP2C8
inhibitor)
o Theophylline
o Drugs having significant pre-systemic clearance via UGT1A1 in the
intestine
Respective substances must be stopped at least 7 days before randomization.21. Women of childbearing potential (women are considered of
childbearing potential if they are not surgically sterile or
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method