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

NCT ID: NCT00887588

Last Updated: 2015-08-25

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

307 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-11-30

Study Completion Date

2011-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Chronic Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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LCZ696

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.

Group Type EXPERIMENTAL

LCZ696

Intervention Type DRUG

50 mg, 100 mg and 200 mg tablets

Placebo

Intervention Type DRUG

matching placebo to LCZ696 and Valsartan

Valsartan

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.

Group Type ACTIVE_COMPARATOR

Valsartan

Intervention Type DRUG

40 mg, 80 mg and 160 mg tablets

Placebo

Intervention Type DRUG

matching placebo to LCZ696 and Valsartan

Interventions

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LCZ696

50 mg, 100 mg and 200 mg tablets

Intervention Type DRUG

Valsartan

40 mg, 80 mg and 160 mg tablets

Intervention Type DRUG

Placebo

matching placebo to LCZ696 and Valsartan

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Novartis

Role: STUDY_DIRECTOR

Novartis

Locations

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Novartis Investigative Site

Little Rock, Arkansas, United States

Site Status

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Chicago, Illinois, United States

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Detroit, Michigan, United States

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Grand Island, Nebraska, United States

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Lincoln, Nebraska, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Hillsboro, Oregon, United States

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Wyomissing, Pennsylvania, United States

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Nashville, Tennessee, United States

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Houston, Texas, United States

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Caba, Buenos Aires, Argentina

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Ciudad Autonoma de Bs As, Buenos Aires, Argentina

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Ramos Mejía, Buenos Aires, Argentina

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San Martín, Buenos Aires, Argentina

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Corrientes, Corrientes Province, Argentina

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Córdoba, Córdoba Province, Argentina

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Córdoba, Córdoba Province, Argentina

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Rosario, Santa Fe Province, Argentina

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Santa Fe, Santa Fe Province, Argentina

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Santa Fe, Santa Fe Province, Argentina

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San Miguel de Tucumán, Tucumán Province, Argentina

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Goiânia, Goiás, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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São José do Rio Preto, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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Brampton, Ontario, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Göttingen, , Germany

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Hyderabad, Andhra Pradesh, India

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Hyderabad, Andhra Pradesh, India, India

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Mangalore, Karnataka, India

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Manipal, Karnataka, India

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Mumbai, Maharashtra, India

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Nagpur, Maharashtra, India

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Nagpur, Maharashtra, India

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New Delhi, National Capital Territory of Delhi, India

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Jaipur, Rajasthan, India

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Jaipur, Rajasthan, India

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Hyderabad, , India

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Bergamo, BG, Italy

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Cosenza, CS, Italy

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Pisa, PI, Italy

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Casorate Primo, PV, Italy

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Sarzana, SP, Italy

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San Daniele del Friuli, UD, Italy

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Somma Lombardo, VA, Italy

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Ede, Netherlands, Netherlands

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Amsterdam, , Netherlands

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Delft, , Netherlands

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Goes, , Netherlands

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Groningen, , Netherlands

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Heerenveen, , Netherlands

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Heerlen, , Netherlands

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Hengelo, , Netherlands

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Warszawa/Anin, Poland, Poland

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Piotrkow Trybunalski, , Poland

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Sieradz, , Poland

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Wroclaw, , Poland

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Wroclaw, , Poland

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Craiova, Jud. Dolj, Romania

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Craiova, Jud.Dolj, Romania

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Baia Mare, , Romania

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Piteşti, , Romania

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Moscow, , Russia

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Moscow, , Russia

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S.-Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Singapore, Singapore, Singapore

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Singapore, Singapore, Singapore

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Seville, Andalusia, Spain

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L'Hospitalet de Llobregat, Barcelona, Spain

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A Coruña, Galicia, Spain

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Santiago de Compostela, Galicia, Spain

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Madrid, Madrid, Spain

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Madrid, Madrid, Spain

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Alicante, Valencia, Spain

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Caracas, Distrito Federal, Venezuela

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Maracaibo, Zulia, Venezuela

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Countries

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United States Argentina Brazil Canada Germany India Italy Netherlands Poland Romania Russia Singapore Spain Venezuela

References

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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.

Reference Type BACKGROUND
PMID: 22932717 (View on PubMed)

Myhre PL, Liu Y, Kulac IJ, Claggett BL, Prescott MF, Felker GM, Butler J, Pina IL, Rouleau JL, Zile MR, McMurray JJV, Ward JH, Solomon SD, Januzzi JL. Changes in mid-regional pro-adrenomedullin during treatment with sacubitril/valsartan. Eur J Heart Fail. 2023 Aug;25(8):1396-1405. doi: 10.1002/ejhf.2957. Epub 2023 Jul 11.

Reference Type DERIVED
PMID: 37401523 (View on PubMed)

Biering-Sorensen T, Lassen MCH, Shah A, Claggett B, Zile M, Pieske B, Pieske-Kraigher E, Voors A, Shi V, Lefkowitz M, Packer M, McMurray JJV, Solomon SD; PARAMOUNT Investigators. The Effect of Sacubitril/Valsartan on Left Ventricular Myocardial Deformation in Heart Failure with Preserved Ejection Fraction (PARAMOUNT trial). J Card Fail. 2023 Jun;29(6):968-973. doi: 10.1016/j.cardfail.2023.03.019. Epub 2023 Apr 7.

Reference Type DERIVED
PMID: 37031887 (View on PubMed)

Januzzi JL Jr, Packer M, Claggett B, Liu J, Shah AM, Zile MR, Pieske B, Voors A, Gandhi PU, Prescott MF, Shi V, Lefkowitz MP, McMurray JJV, Solomon SD. IGFBP7 (Insulin-Like Growth Factor-Binding Protein-7) and Neprilysin Inhibition in Patients With Heart Failure. Circ Heart Fail. 2018 Oct;11(10):e005133. doi: 10.1161/CIRCHEARTFAILURE.118.005133.

Reference Type DERIVED
PMID: 30354399 (View on PubMed)

Zile MR, Jhund PS, Baicu CF, Claggett BL, Pieske B, Voors AA, Prescott MF, Shi V, Lefkowitz M, McMurray JJ, Solomon SD; Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction (PARAMOUNT) Investigators. Plasma Biomarkers Reflecting Profibrotic Processes in Heart Failure With a Preserved Ejection Fraction: Data From the Prospective Comparison of ARNI With ARB on Management of Heart Failure With Preserved Ejection Fraction Study. Circ Heart Fail. 2016 Jan;9(1):e002551. doi: 10.1161/CIRCHEARTFAILURE.115.002551.

Reference Type DERIVED
PMID: 26754625 (View on PubMed)

Andersen MB, Simonsen U, Wehland M, Pietsch J, Grimm D. LCZ696 (Valsartan/Sacubitril)--A Possible New Treatment for Hypertension and Heart Failure. Basic Clin Pharmacol Toxicol. 2016 Jan;118(1):14-22. doi: 10.1111/bcpt.12453. Epub 2015 Sep 4.

Reference Type DERIVED
PMID: 26280447 (View on PubMed)

Jhund PS, Claggett BL, Voors AA, Zile MR, Packer M, Pieske BM, Kraigher-Krainer E, Shah AM, Prescott MF, Shi V, Lefkowitz M, McMurray JJ, Solomon SD; PARAMOUNT Investigators. Elevation in high-sensitivity troponin T in heart failure and preserved ejection fraction and influence of treatment with the angiotensin receptor neprilysin inhibitor LCZ696. Circ Heart Fail. 2014 Nov;7(6):953-9. doi: 10.1161/CIRCHEARTFAILURE.114.001427. Epub 2014 Oct 2.

Reference Type DERIVED
PMID: 25277997 (View on PubMed)

Santos AB, Kraigher-Krainer E, Gupta DK, Claggett B, Zile MR, Pieske B, Voors AA, Lefkowitz M, Bransford T, Shi V, Packer M, McMurray JJ, Shah AM, Solomon SD; PARAMOUNT Investigators. Impaired left atrial function in heart failure with preserved ejection fraction. Eur J Heart Fail. 2014 Oct;16(10):1096-103. doi: 10.1002/ejhf.147. Epub 2014 Aug 19.

Reference Type DERIVED
PMID: 25138249 (View on PubMed)

Kraigher-Krainer E, Shah AM, Gupta DK, Santos A, Claggett B, Pieske B, Zile MR, Voors AA, Lefkowitz MP, Packer M, McMurray JJ, Solomon SD; PARAMOUNT Investigators. Impaired systolic function by strain imaging in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2014 Feb 11;63(5):447-56. doi: 10.1016/j.jacc.2013.09.052. Epub 2013 Oct 30.

Reference Type DERIVED
PMID: 24184245 (View on PubMed)

Other Identifiers

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2009-010208-27

Identifier Type: -

Identifier Source: secondary_id

CLCZ696B2214

Identifier Type: -

Identifier Source: org_study_id

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