LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00887588
First received: April 22, 2009
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

The study will assess the effects of 36 weeks of treatment with LCZ696 compared to valsartan on N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) in patients with chronic heart failure and preserved left-ventricular ejection fraction.


Condition Intervention Phase
Chronic Heart Failure
Drug: LCZ696
Drug: Valsartan
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A 36-week, Randomized, Double-blind, Multi-center, Parallel Group, Active Controlled Study to Evaluate the Efficacy, Safety and Tolerability of LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in log-scale in NT-proBNP [ Time Frame: Baseline, 12 weeks, 36 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in log-scale in BNP, MR-proBNP, cGMP [ Time Frame: Baseline, 12 weeks, 36 weeks ] [ Designated as safety issue: No ]
  • Change in echocardiography parameters [ Time Frame: Baseline, 12 weeks, 36 weeks ] [ Designated as safety issue: No ]
  • Change in the overall summary score and individual domain score of the Kansas City Cardiomyopathy questionnaire [ Time Frame: Baseline, 12 weeks, 36 weeks ] [ Designated as safety issue: No ]
  • Change in clinical composite score (NYHA and global patient assessment score) time frame [ Time Frame: Baseline, 12 weeks, 36 weeks ] [ Designated as safety issue: Yes ]
  • class indicators of signs and symptoms of heart failure at each visit [ Time Frame: Baseline, 12 weeks, 36 weeks ] [ Designated as safety issue: No ]

Enrollment: 307
Study Start Date: November 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LCZ696
LCZ696 50 mg titrated to 100 mg and 200 mg
Drug: LCZ696
LCZ696 50 mg titrated to 100 mg and 200 mg
Active Comparator: Valsartan
Valsartan 40 mg titrated to 80 mg and 160 mg
Drug: Valsartan
Valsartan 40 mg titrated to 80 mg and 160 mg

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with documented stable chronic heart failure (NYHA II-IV):

    • LVEF ≥ 45% (local measurement, assessed by echocardiography, MUGA, CT scan, MRI or ventricular angiography)
    • the ejection fraction must have been obtained within 6 months prior to randomization or after any MI or other event that would affect ejection fraction.
  • Plasma NT-proBNP > 500 pg/ml at Visit 1.
  • Patients with documented stable chronic heart failure (NYHA II-IV).
  • Patients receiving ACE inhibitors (ACEi), an angiotensin receptor blockers (ARB) and/or a beta blockers must be on a stable dose of these medications stable for the 1 month period prior to Visit 1.
  • Patients must be on diuretic therapy prior to Visit 1 (flexible dosing is permitted).
  • Patients with a controlled systolic BP, defined as a target systolic BP less than 140 mm Hg; participants with BP up to and including 160 mm Hg are eligible for enrollment if they are on three or more medications to control BP at randomization (Visit 2).
  • Patients with at least one of the following symptoms at the time of screening (Visit 1):

    • Dyspnea on exertion
    • Orthopnea
    • Paroxysmal nocturnal dyspnea
    • Peripheral edema
  • Patients must have an eGFR ≥ 30 ml/min/1.73 m2 at Visit 1 (calculated by the Modification of Diet in Renal Disease formula).
  • Patients with a potassium ≤5.2 mmol/l at Visit 1.

Exclusion Criteria:

  • Patients with a prior LVEF reading <45%, at any time.
  • Patients who require treatment with both an ACE inhibitor and an ARB.
  • Isolated right heart failure due to pulmonary disease.
  • Dyspnea and/or edema from non-cardiac causes, such as lung disease, anemia, or severe obesity.
  • Presence of hemodynamically significant mitral and /or aortic valve disease.
  • Presence of hemodynamically significant obstructive lesions of left ventricular outflow tract, including aortic stenosis.
  • Presence of hypertrophic obstructive cardiomyopathy.
  • Other protocol-defined inclusion/exclusion criteria may apply
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00887588

  Hide Study Locations
Locations
United States, Arkansas
Novartis Investigative Site
Little Rock, Arkansas, United States, 72205
United States, Illinois
Novartis Investigative Site
Chicago, Illinois, United States, 60657
United States, Michigan
Novartis Investigative Site
Detroit, Michigan, United States, 48201
United States, Nebraska
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Grand Island, Nebraska, United States, 68803
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Lincoln, Nebraska, United States, 68506
United States, Oklahoma
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Oklahoma City, Oklahoma, United States, 73120
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Tulsa, Oklahoma, United States, 74133
United States, Oregon
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Hillsboro, Oregon, United States, 97123
United States, Pennsylvania
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Wyomissing, Pennsylvania, United States, 19610
United States, Tennessee
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Nashville, Tennessee, United States, 37203
United States, Texas
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Houston, Texas, United States, 77025
Argentina
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Caba, Buenos Aires, Argentina, C1408INH
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Ciudad Autonoma de Bs As, Buenos Aires, Argentina, C1119ACN
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Ramos Mejia, Buenos Aires, Argentina, B1704ETD
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San Martin, Buenos Aires, Argentina, B1650CSQ
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Rosario, Santa Fe, Argentina, S200CVD
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San Miguel de Tucuman, Tucuman, Argentina, T4000EBR
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Cordoba, Argentina, X5000EVQ
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Cordoba, Argentina, X5000EPU
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Corrientes, Argentina, W3400
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Santa Fe, Argentina, S3000FWO
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Santa Fe, Argentina, 3000
Brazil
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Goiania, GO, Brazil, 74605-050
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Porto Alegre, RS, Brazil, 90610-000
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Sao Jose do Rio Preto, SP, Brazil, 15150-210
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São Paulo, SP, Brazil, 05403-000
Canada, Ontario
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Brampton, Ontario, Canada, L6Z 4N5
Canada, Quebec
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Montreal, Quebec, Canada, H3G 1A4
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Montreal, Quebec, Canada, H3A 1A1
Germany
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Göttingen, Germany, D-37075
India
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Hyderabad, Andhra Pradesh, INDIA, India, 500034
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Hyderabad, Andhra Pradesh, India, 500012
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New Delhi, Delhi, India, 110060
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Mangalore, Karnataka, India, 575002
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Manipal, Karnataka, India, 576104
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Mumbai, Maharashtra, India, 400 022
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Nagpur, Maharashtra, India, 44000033
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Nagpur, Maharashtra, India, 440012
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Jaipur, Rajasthan, India, 302004
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Jaipur, Rajasthan, India, 302001
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Hyderabad, India, 500 063
Italy
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Bergamo, BG, Italy, 24128
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Cosenza, CS, Italy, 87100
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Vimercate, MI, Italy, 200059
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Pisa, PI, Italy, 56124
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Casorate Primo, PV, Italy, 27022
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Sarzana, SP, Italy, 19038
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San Daniele Del Friuli, UD, Italy, 33038
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Somma Lombardo, VA, Italy, 21019
Netherlands
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Amsterdam, Netherlands, 1105 AZ
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Delft, Netherlands, NL 2625 AD
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Ede, Netherlands, 6710 HN
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Goes, Netherlands, 4462 RA
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Groningen, Netherlands, 9713 GZ
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Heerenveen, Netherlands, 8441 PW
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Heerlen, Netherlands, 6419 PC
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Hengelo, Netherlands, 7555 DL
Poland
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Katowice, Poland, 40-530
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Krakow, Poland, 30-082
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Piotrkow Trybunalski, Poland, 97-300
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Sieradz, Poland, 98-200
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Tarnow, Poland, 33-100
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Warszawa/Anin, Poland, 04-761
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Wroclaw, Poland, 50-981
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Wroclaw, Poland, 51-124
Romania
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Craiova, Jud. Dolj, Romania, 200147
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Craiova, Jud.Dolj, Romania, 200235
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Baia Mare, Romania, 430031
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Pitesti, Romania, 110114
Russian Federation
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Moscow, Russian Federation, 121552
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Moscow, Russian Federation, 117292
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S.-Petersburg, Russian Federation, 196247
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Saint-Petersburg, Russian Federation, 194044
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Saint-Petersburg, Russian Federation, 197341
Singapore
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Singapore, Singapore, 168752
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Singapore, Singapore, 119074
Spain
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Sevilla, Andalucia, Spain, 41009
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Hospitalet de Llobregat, Barcelona, Spain, 08907
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Alicante, Comunidad Valenciana, Spain, 03004
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A Coruña, Galicia, Spain, 15006
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Santiago de Compostela, Galicia, Spain, 15706
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Madrid, Spain, 28034
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Madrid, Spain, 28046
Venezuela
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Caracas, Distrito Capital, Venezuela, 1010
Novartis Investigative Site
Maracaibo, Estado Zulia, Venezuela, 4011
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Director: Novartis Novartis
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00887588     History of Changes
Other Study ID Numbers: CLCZ696B2214, 2009-010208-27
Study First Received: April 22, 2009
Last Updated: June 25, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health
Brazil: Ministry of Health
Canada: Health Canada
India: Ministry of Health
Italy: Ministry of Health
Netherlands: Medicines Evaluation Board (MEB)
Poland: Ministry of Health
Romania: Ministry of Public Health
Russia: Pharmacological Committee, Ministry of Health
Singapore: Health Sciences Authority
Spain: Ministry of Health
Venezuela: Ministry of Health and Social Development
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
Chronic heart failure
preserved ejection fraction
cardiovascular disease
NT-proBNP
biomarkers
Heart failure with preserved left-ventricular ejection
fraction

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Valsartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014