Chronic Heart Failure MedDRA version: 15.1 Level: LLT Classification code 10008502 Term: CHF System Organ Class: 100000004849
Conditions
Interventions
Product Name: LCZ696
Product Code: LCZ696
Pharmaceutical Form: Film-coated tablet
CAS Number: 936623-90-4
Current Sponsor code: LCZ696
Concentration unit: mg milligram(s)
Concentration type: equal
Con
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Outpatients = 18 years of age, male or female. 2. Patients with a diagnosis of CHF NYHA class II-IV and reduced ejection fraction: • LVEF = 35% at Visit 1 (any local measurement, made within the past 6 months using echocardiography, MUGA, CT scanning, MRI, or ventricular angiography is acceptable, provided no subsequent measurement above 35%) • BNP = 150 pg/ml (or NT-proBNP = 600 pg/ml) at Visit 1 OR BNP = 100 pg/mL (or NT-proBNP = 400 pg/ml) at Visit 1 and a hospitalization for HF within the last 12 months 3. Patients must be on an ACEI or an ARB at a stable dose of at least enalapril 10 mg/d or equivalent for at least 4 weeks before Visit 1. • For this protocol, doses of other ACEIs considered to be equivalent to enalapril 10 mg/d include benazepril 20 mg/d, captopril 100 mg/d, cilazapril 2.5 mg/d, fosinopril 20 mg/d,lisinopril 10 mg/d, moexipril 7.5 mg/d, perindopril 4 mg/d, quinapril 20 mg/d, ramipril 5 mg/d, trandolapril 2 mg/d, and zofenopril 30 mg/d. • For this protocol, doses of ARBs considered to be equivalent to enalapril 10 mg/d include candesartan 16 mg/d, eprosartan 400 mg/d, irbesartan 150 mg/d, losartan 50 mg/d, olmesartan 10 mg/d, telmisartan 40 mg/d, and valsartan 160 mg/d. 4. Patients must be treated with a ß-blocker, unless contraindicated or not tolerated, at a stable dose for at least 4 weeks prior to Visit 1 (reason should be documented for patients not on CHF target doses per local guidelines, or in absence of that medication). 5. An aldosterone antagonist should also be considered in all patients, taking account of renal function, serum potassium and tolerability. If given, the dose of aldosterone antagonist should be optimized according to guideline recommendations and patient tolerability, and should be stable for at least 4 weeks prior to Visit 1. Other evidence-based therapy for heart failure should also be considered e.g. cardiac resynchronization therapy and an implantable cardioverter-defibrillator in selected patients, as recommended by guidelines. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of hypersensitivity or allergy to any of the study drugs, drugs of similar chemical classes, ACEIs, ARBs, or NEP inhibitors as well as known or suspected contraindications to the study drugs. 2. Previous history of intolerance to recommended target doses of ACEIs or ARBs. 3. Known history of angioedema. 4. Requirement of treatment with both ACEIs and ARBs. 5. Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy). 6. Symptomatic hypotension and/or a systolic blood pressure (SBP) 35% decline in eGFR between Visit 1 and Visit 3 or between Visit 1 and Visit 5. 8. Serum potassium > 5.2 mmol/L at Visit 1 (screening) or > 5.4 mmol/L at Visit 3 or Visit 5 (randomization). 9. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major CV surgery, percutaneous coronary intervention (PCI) or carotid angioplasty within the 3 months prior to Visit 1. 10. Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 6 months after Visit 1. 11. Implantation of a cardiac resynchronization therapy pacemaker (CRT-P) or a cardiac resynchronization therapy defibrillator (CRT-D) or upgrading of an existing conventional pacemaker or an implantable cardioverter defibrillator (ICD) to CRT device within 3 months before Visit 1 or intent to implant such a device. Also, patients who had implantation of a conventional pacemaker or an ICD or had a revision of a pacemaker or other device leads within 1 month before Visit 1 are excluded. 12. Heart transplant or ventricular assistance device (VAD) or intent to transplant (on transplant list) or implant a VAD. 13. History of severe pulmonary disease. 14. Diagnosis of peripartum or chemotherapy induced cardiomyopathy within the 12 months prior to Visit 1. 15. Documented untreated ventricular arrhythmia with syncopal episodes within the 3 months prior to Visit 1. 16. Symptomatic bradycardia or second or third degree heart block without a pacemaker. 17. Presence of hemodynamically significant mitral and/or aortic valve disease, except mitral regurgitation secondary to left ventricular dilatation. 18. Presence of other hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic and sub-aortic stenosis. 19. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs, including but not limited to any of the following: • History of active inflammatory bowel disease during the 12 months before Visit 1. • Active duodenal or gastric ulcers during the 3 months prior to Visit 1. • Evidence of hepatic disease as determined by any one of the following: AST or ALT values exceeding 2 x upper limit of normal (ULN) at Visit 1, history of hepatic encephalopathy, history of esophageal varices, or history of portacaval shunt. • Current treatment with cholestyramine or colestipol resins. 20. Presence of any other disease with a life expectancy of < 5 years. 21. Presence of bilateral renal artery stenosis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To test if LCZ696 is superior to enalapril in delaying time to first occurrence of the composite endpoint, which is defined as either CV death or HF hospitalization, in patients with CHF (NYHA class II – IV) and reduced ejection fraction;Secondary Objective: • To test whether LCZ696, compared to enalapril, improves the clinical summary score for HF symptoms and physical limitations (as assessed by the Kansas City Cardiomyopathy Questionnaire [KCCQ]) at 8 months. • To test whether LCZ696 is superior to enalapril in delaying the time to all-cause mortality. • To test whether LCZ696 is superior to enalapril in delaying time to first occurrence to either (1) a 50% decline in estimated glomerular filtration rate (eGFR) relative to baseline, (2) >30 mL decline in eGFR relative to baseline, or (3) reaching end stage renal disease (ESRD). ;Primary end point(s): Time to first occurrence of the composite endpoint, which is defined as either CV death or HF hospitalization | — |
Countries
Belgium, Bulgaria, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Iceland, Italy, Latvia, Lithuania, Netherlands, Portugal, Romania, Slovakia, Spain, Sweden, United Kingdom
Outcome results
None listed