Study of Efficacy and Safety of LCZ696 in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction (PARALLEL-HF)
- Conditions
- Heart Failure With Reduced Ejection Fraction (HF-rEF)
- Registration Number
- JPRN-jRCT2080222891
- Lead Sponsor
- ovartis Pharma K.K.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 220
1. Written informed consent must be obtained before any assessment is performed.
2. Outpatients 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 also acceptable, provided no subsequent measurement above 35%)
-NT-proBNP >= 600 pg/ml at Visit 1 OR NT-proBNP >= 400 pg/ml at Visit 1 and a hospitalization for HF within the last 12 months (according to central laboratory measurements)
3. Patients must be on an ACEI or an ARB at a stable dose for at least 4 weeks before Visit 1.
4. Patients must be treated with a beta-blocker, unless contraindicated or not tolerated, at a stable dose for at least 4 weeks prior to Visit 1 (reason should be documented if patients reported contraindications or intolerance).
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 HF should also be considered e.g. cardiac resynchronization therapy and an implantable cardioverter-defibrillator in selected patients, as recommended by guidelines.
1. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes, ACEIs, ARBs, NEP inhibitors as well as known or suspected contraindications to the study drugs.
2. Previous documented history of intolerance to 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 SBP < 100 mmHg at screening or < 95 mmHg at the end of run-in.
7. Estimated GFR < 30 mL/min/1.73 m2 as measured by the Japanese formula at screening, or the end of run-in or > 35% decline in eGFR between screening and end of run-in (according to local measurements).
8. Serum potassium > 5.2 mmol/L (mEq/L) at screening or > 5.4 mmol/L (mEq/L) at the end of run-in (according to local measurements).
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. Documented untreated ventricular arrhythmia with syncopal episodes within the 3 months prior to Visit 1.
11. Symptomatic bradycardia or second (except asymptomatic Wenckebach block) or third degree heart block without a pacemaker.
12. Presence of hemodynamically significant mitral and/or aortic valve disease, except mitral regurgitation secondary to left ventricular dilatation.
13. Presence of other hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic and sub-aortic stenosis.
14. Presence of bilateral renal artery stenosis.
Other protocol defined inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method safety<br>efficacy<br>Time to the first occurrence of the composite endpoint, which is defined as either cardiovascular (CV) death or heart failure (HF) hospitalization [ Time Frame: up tp 40 months ]
- Secondary Outcome Measures
Name Time Method safety<br>efficacy<br>Changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline at predefined time points [ Time Frame: Baseline, Weeks 4, 8 and Month 6 ] <br><br>safety<br>efficacy<br>Time to the first occurrence of CV death, HF hospitalization or intensification of treatments due to documented episode(s) of worsening HF [ Time Frame: up tp 40 months ] <br><br>safety<br>efficacy<br>Changes in New York Heart Association (NYHA) classification from baseline at predefined timepoints [ Time Frame: Baseline, Weeks 4, 8 and Month 6 ]<br><br>safety<br>efficacy<br>Changes in clinical summary score for heart failure symptoms and physical limitations from baseline [ Time Frame: Baseline, Week 8 and Month 6 ] <br>Clinical summary score for heart failure symptoms and physical limitations will be assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)