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

Novartis

Status and phase: Completed; Phase 2

Conditions: Chronic Heart Failure

Treatments: Drug: Valsartan; Drug: Placebo; Drug: LCZ696

Study type: Interventional

Funder types: Industry

Identifiers

NCT00887588

2009-010208-27

CLCZ696B2214

Details and patient eligibility

About

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.

Enrollment: 307 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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307 participants in 2 patient groups

LCZ696

Experimental group

Description:

During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 50 mg LCZ696 for 1- 2 weeks, then uptitrated to 100 mg bid for 1 -2 weeks, and thereafter, uptitrated to 200 mg bid.

Treatment:

Drug: LCZ696

Drug: Placebo

Valsartan

Active Comparator group

Description:

During a single blind, run-in period, participants received placebo. Then at randomization (double blind treatment period), participants started with 40 mg Valsartan twice daily (bid) for 1 - 2 weeks, then were uptitrated to 80 mg bid for 1 -2 weeks, and thereafter, uptitrated to 160 mg bid.

Treatment:

Drug: Valsartan

Drug: Placebo