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

April 22, 2009
January 2, 2013
November 2009
December 2011   (final data collection date for primary outcome measure)
Change in log-scale in NT-proBNP [ Time Frame: Baseline, 12 weeks, 36 weeks ] [ Designated as safety issue: No ]
Change in log-scale in NT-proBNP [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00887588 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Change in log-scale in BNP, MR-proBNP, cGMP [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change in echocardiography parameters [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Class indicators of signs and symptoms of heart failure at each visit [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change in the overall summary score and individual domain score of the Kansas City Cardiomyopathy questionnaire [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change in clinical composite score (NYHA and global patient assessment score) time frame [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction
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

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Chronic Heart Failure
  • Drug: LCZ696
    LCZ696 50 mg titrated to 100 mg and 200 mg
  • Drug: Valsartan
    Valsartan 40 mg titrated to 80 mg and 160 mg
  • Experimental: LCZ696
    LCZ696 50 mg titrated to 100 mg and 200 mg
    Intervention: Drug: LCZ696
  • Active Comparator: Valsartan
    Valsartan 40 mg titrated to 80 mg and 160 mg
    Intervention: Drug: Valsartan
Solomon SD, Zile M, Pieske B, Voors A, Shah A, Kraigher-Krainer E, Shi V, Bransford T, Takeuchi M, Gong J, Lefkowitz M, Packer M, McMurray JJ; Prospective comparison of ARNI with ARB on Management Of heart failUre with preserved ejectioN fracTion (PARAMOUNT) Investigators. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet. 2012 Oct 20;380(9851):1387-95. doi: 10.1016/S0140-6736(12)61227-6. Epub 2012 Aug 26.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
682
December 2011
December 2011   (final data collection date for primary outcome measure)

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
Both
40 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Brazil,   Canada,   Germany,   India,   Italy,   Netherlands,   Poland,   Romania,   Russian Federation,   Singapore,   Spain,   Venezuela
 
NCT00887588
CLCZ696B2214, 2009-010208-27
No
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Director: Novartis Novartis
Novartis
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP