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: January 2, 2013
Last verified: January 2013
  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: 682
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00887588

  Show 85 Study Locations
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: January 2, 2013
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 April 20, 2014