Study of Efficacy and Safety of LCZ696 in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction.

A Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction.

ClinicalTrials.gov Identifier: NCT02468232

Novartis Reference Number: CLCZ696B1301

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

The purpose of this study is to assess the effect of LCZ696 at a target dose of 200 mg b.i.d. compared to enalapril 10 mg b.i.d., in addition to the background heart failure (HF) treatment, on delaying time to first occurrence of either cardiovascular (CV) death or HF hospitalization events in Japanese patients with stable chronic heart failure (CHF), New York Heart Association (NYHA) classes II-IV and reduced ejection fraction (left ventricular ejection fraction (LVEF) ≤ 35%).

Condition 
Heart Failure With Reduced Ejection Fraction (HF-rEF)
Phase 
Phase 3
Overall status 
Active, not recruiting
Enrollment count 
225 participants
Start date 
Jun 15, 2015
Completion date 
Aug 31, 2020
Gender 
All
Age(s)
20 Years and older (Adult, Older Adult)

Interventions

Drug
LCZ696
LCZ696 50 mg, 100 mg, 200 mg film-coated tablets
Drug
Enalapril
Enalapril 2.5 mg, 5 mg, 10 mg film-coated tablets
Drug
Placebo to LCZ696
Placebo to match LCZ696 50 mg, 100 mg and 200 mg film-coated tablets
Drug
Placebo to Enalapril
Placebo to match enalapril 2.5 mg, 5 mg and 10 mg film-coated tablets

Eligibility Criteria

Inclusion Criteria:

Written informed consent must be obtained before any assessment is performed.
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)
Patients must be on an ACEI or an ARB at a stable dose for at least 4 weeks before Visit 1.
Patients must be treated with a β-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).
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.

Exclusion Criteria:

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.
Previous documented history of intolerance to ACEIs or ARBs.
Known history of angioedema.
Requirement of treatment with both ACEIs and ARBs.
Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy).
Symptomatic hypotension and/or a SBP < 100 mmHg at screening or < 95 mmHg at the end of run-in.
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).
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).
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.
Documented untreated ventricular arrhythmia with syncopal episodes within the 3 months prior to Visit 1.
Symptomatic bradycardia or second (except asymptomatic Wenckebach block) or third degree heart block without a pacemaker.
Presence of hemodynamically significant mitral and/or aortic valve disease, except mitral regurgitation secondary to left ventricular dilatation.
Presence of other hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic and sub-aortic stenosis.
Presence of bilateral renal artery stenosis.

Other protocol defined inclusion/exclusion criteria may apply.

Study Locations

Japan
Novartis Investigative Site
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Nagoya, 453-8511
Aichi
Japan
Novartis Investigative Site
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Seto-city, 489-8642
Aichi
Japan
Novartis Investigative Site
-
Chikushino-city, 818-8516
Fukuka
Japan
Novartis Investigative Site
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Fukuoka city, 812-8582
Fukuoka
Japan
Novartis Investigative Site
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Fukuoka-city, 810-0001
Fukuoka
Japan
Novartis Investigative Site
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Iizuka-city, 820-8505
Fukuoka
Japan
Novartis Investigative Site
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Kurume-city, 830-8577
Fukuoka
Japan
Novartis Investigative Site
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Fukushima city, 960 1295
Fukushima
Japan
Novartis Investigative Site
-
Koriyama city, 963-8052
Fukushima
Japan
Novartis Investigative Site
-
Maebashi city, 371 8511
Gunma
Japan
Novartis Investigative Site
-
Hatsukaichi city, 738 8503
Hiroshima
Japan
Novartis Investigative Site
-
Onomichi-city, 722-8503
Hiroshima
Japan
Novartis Investigative Site
-
Asahikawa-city, 078-8211
Hokkaido
Japan
Novartis Investigative Site
-
Otaru-city, 047-8510
Hokkaido
Japan
Novartis Investigative Site
-
Sapporo city, 060 8648
Hokkaido
Japan
Novartis Investigative Site
-
Amagasaki city, 660 8550
Hyogo
Japan
Novartis Investigative Site
-
Takarazuka-city, 665-0873
Hyogo
Japan
Novartis Investigative Site
-
Morioka, 020 0066
Iwate
Japan
Novartis Investigative Site
-
Takamatsu city, 760 8557
Kagawa
Japan
Novartis Investigative Site
-
Kawasaki-city, 211-8533
Kanagawa
Japan
Novartis Investigative Site
-
Kawasaki-city, 216-8511
Kanagawa
Japan
Novartis Investigative Site
-
Yokohama-city, 227-8501
Kanagawa
Japan
Novartis Investigative Site
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Kumamoto City, 860-8556
Kumamoto
Japan
Novartis Investigative Site
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Kyoto-city, 607-8062
Kyoto
Japan
Novartis Investigative Site
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Uji-city, 611-0042
Kyoto
Japan
Novartis Investigative Site
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Sendai city, 980 8574
Miyagi
Japan
Novartis Investigative Site
-
Miyhazaki-city, 880-0834
Miyazaki
Japan
Novartis Investigative Site
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Saku-city, 3850051
Nagano
Japan
Novartis Investigative Site
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Kashihara city, 634 8522
Nara
Japan
Novartis Investigative Site
-
Oita-city, 870-0192
Oita
Japan
Novartis Investigative Site
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Okayama-city, 700-8558
Okayama
Japan
Novartis Investigative Site
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Kishiwada-city, 596-0042
Osaka
Japan
Novartis Investigative Site
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Osaka-city, 530-8480
Osaka
Japan
Novartis Investigative Site
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Osaka-city, 559-0012
Osaka
Japan
Novartis Investigative Site
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Takatsuki, 569-1096
Osaka
Japan
Novartis Investigative Site
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Toyonaka-city, 560-8565
Osaka
Japan
Novartis Investigative Site
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Tokorozawa-city, 359-1141
Saitama
Japan
Novartis Investigative Site
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Kusatsu city, 525 8585
Shiga
Japan
Novartis Investigative Site
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Kakegawa-city, 436-8555
Shizuoka
Japan
Novartis Investigative Site
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Shizuoka-city, 420-8630
Shizuoka
Japan
Novartis Investigative Site
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Shimotsuke, 329-0498
Tochigi
Japan
Novartis Investigative Site
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Akishima-city, 196-0003
Tokyo
Japan
Novartis Investigative Site
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Bunkyo-ku, 113-8603
Tokyo
Japan
Novartis Investigative Site
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Chiyoda-ku, 101-8309
Tokyo
Japan
Novartis Investigative Site
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Chuo ku, 104-8560
Tokyo
Japan
Novartis Investigative Site
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Hachioji-city, 192-0918
Tokyo
Japan
Novartis Investigative Site
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Itabashi-ku, 173-8610
Tokyo
Japan
Novartis Investigative Site
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Shinagawa-ku, 142-8666
Tokyo
Japan
Novartis Investigative Site
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Yonago-city, 683-8504
Tottori
Japan
Novartis Investigative Site
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Shunan-city, 745-8522
Yamaguchi
Japan
Novartis Investigative Site
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Kofu-city, 400-8506
Yamanashi
Japan
Novartis Investigative Site
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Saitama, 330 8503
-
Japan

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