Phase 2
N=301
LCZ696 Compared to Valsartan in Patients With Chronic Heart Failure and Preserved Left-ventricular Ejection Fraction
Chronic Heart Failure
Bottom Line
View on ClinicalTrials.gov: NCT00887588 ↗Enrolled (actual)
301
Serious AEs
17.3%
Results posted
Aug 2015
Primary outcome: Primary: Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) — 0.83; 1.08 ratio: endpoint/baseline (pg/mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- LCZ696 (Drug); Valsartan (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Dec 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) |
0.83; 1.08 | — |
| SECONDARY Change From Baseline in NT-proBNP and Brain Natriuretic Peptide (BNP) |
0.78; 0.92; 1.14; 0.95 | — |
| SECONDARY Change From Baseline in Plasma Cyclic Guanine Monophosphate (cGMP) |
0.90; 0.85 | — |
| SECONDARY Change From Baseline in Echocardiography (ECHO) Parameters: Left Ventricular End (LVE) Diastolic Diameter, LVE Systolic Diameter, Septal End Diastolic Thickness, Posterior LV Wall End Diastolic Thickness, Relative Wall Thickness, Left Atrial Dimension |
-0.23; -0.19; -0.12; -0.11; 0.01; 0.01 | — |
| SECONDARY Change From Baseline in Echocardiography Parameters: LVE Diastolic Volume, LVE Systolic Volume, Left Ventricular Stroke Volume, Left Atrial Volume |
-12.66; -14.31; -8.49; -9.64; -4.34; -4.63 | — |
| SECONDARY Change From Baseline in Echocardiography Parameters: Left Ventricular Ejection Fraction |
2.62; 2.90 | — |
| SECONDARY Change From Baseline in Echocardiography Parameters: Left Ventricular Mass |
-11.26; -8.00 | — |
| SECONDARY Change From Baseline in Echocardiography Parameters: Left Ventricular Mass Index |
-3.95; -1.94 | — |
| SECONDARY Change From Baseline in Echocardiography Parameters: Left Atrial Volume Index |
-4.02; -0.88 | — |
| SECONDARY Change From Baseline in Echocardiography Parameters: Ewave Velocity, A Wave Velocity, e' at Septal Mitral Annulus, e' at Lateral Mitral Annulus |
-0.60; 4.12; -0.39; 0.59; 1.00; 0.98 | — |
| SECONDARY Change From Baseline in Echocardiography Parameters: Ratio of E to A Velocity, E/e' Ratio |
0.01; 0.07; -1.18; -0.75 | — |
| SECONDARY Change in Echocardiography Parameters: Isovolumic Relaxation Time |
0.01; 0.01 | — |
| SECONDARY Change From Baseline in Echocardiography Parameters: Tricuspid Regurgitation Velocity |
-0.05; 0.00 | — |
| SECONDARY Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score and Individual Domain Summary Scores |
9.27; 9.88; 6.43; 7.94; 10.38; 9.16 | — |
| SECONDARY Percentage of Participants With Clinical Composite Assessment of Improved, Unchanged or Worsened |
41.7; 32.8; 45.7; 53.6; 12.6; 13.6 | — |
| SECONDARY Percentage of Participants With New York Heart Association (NYHA) Class I, II, II or IV |
0.8; 0.8; 78.7; 81.6; 20.5; 17.6 | — |
| SECONDARY Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) |
-3.68; -7.14 | — |
| SECONDARY Change From Baseline in Serum Creatinine |
5.82; 10.65 | — |
| SECONDARY Change From Baseline in Albumin/Creatinine Ratio |
1.19; 0.74 | — |
| SECONDARY Change From Baseline in Arterial Stiffness Parameters: Brachial Systolic Blood Pressure (SBP), Brachial Diastolic Blood Pressure (DBP), Central Augmentation Pressure, Central Pressure at T1-DP, Central SBP, Central DBP, Central Mean Pressure |
-1.27; 1.47; 1.68; 0.79; -0.21; -0.24 | — |
| SECONDARY Change From Baseline in Arterial Stiffness Parameters: Heart Rate Correct Cen Aug/Pulse Ht |
-0.74; -2.16 | — |
| SECONDARY Change From Baseline in Arterial Stiffness Parameters: Heart Rate |
-0.64; -1.32 | — |
| SECONDARY Change From Baseline in Arterial Stiffness Parameters: Pulse Wave Velocity |
-0.44; -0.74 | — |
| SECONDARY Change From Baseline in Sitting SBP, Sitting DBP and Sitting Pulse Pressure (PP) |
-7.47; -2.18; -5.28; -1.39; -2.24; -1.17 | — |
Summary
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.
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT00887588). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.