Clinical trial NCT00549770: Efficacy and Safety of LCZ696A in Patients With Essential Hypertension
Official title: A Multi-center, Randomized, Double-blind, Placebo and Active Controlled, Parallel Group, Dose Range Study to Evaluate the Efficacy and Safety of LCZ696 Comparatively to Valsartan, and to Evaluate AHU377 to Placebo After 8 Week Treatment in Patients With Essential Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension
Keywords: Hypertension, valsartan, LCZ696
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-10-26
Enrollment: 1334
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was a dose-ranging efficiacy study in patients with essential hypertension to assess the blood pressure lowering effect, and safety of LCZ696 compared to valsartan and placebo. The study will also evaluate the efficacy and safety of AHU377 as compared to placebo.


Eligibility criteria: Inclusion Criteria:

* Male or females from 18 up to and including 75 years
* Patients with mild-to-moderate uncomplicated essential hypertension, untreated or currently taking antihypertensive therapy (monotherapy or combination therapy of 2 drugs; therapy with a fixed dose combination of two active substances represents 2 drugs)
* Untreated patients must have had an office msDBP≥ 95 mmHg at the randomization visit (Visit 3) and the 2 preceding visits (Visits 1 and 2).
* Treated patients must have had an office msDBP≥ 90 mmHG after washout (Visit 2), and a msDBP\> 95 mmHg at baseline (Visit 3);

Exclusion Criteria:

* Severe hypertension (msSBP ≥180 mmHg and/or msDBP ≥110 mmHg)
* History of angioedema, drug-related or otherwise, as reported by the patient
* Type 1 or Type 2 diabetes mellitus (according to the ADA criteria)
* History or evidence of a secondary form of hypertension, such as renal parenchymal hypertension, renovascular hypertension, coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, drug-induced hypertension, unilateral or bilateral renal artery stenosis, pheochromocytoma, polycystic kidney disease, etc.
* History of angina pectoris, myocardial infarction, coronary bypass surgery, ischemic heart disease, surgical or percutaneous arterial intervention of any kind (coronary, carotid or peripheral intervention), stroke, TIA (transient ischemic attack), carotid artery stenosis, aortic aneurysm or peripheral arterial disease

Primary outcomes:
measure: Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
timeFrame: baseline, week 8
Secondary outcomes:
measure: Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
timeFrame: baseline, week 8
measure: Change From Baseline in 24-hour Mean Ambulatory DBP (maDBP) and maSBP
timeFrame: baseline, 8 weeks
measure: Change From Baseline in Daytime maDBP and maSBP
timeFrame: baseline, 8 weeks
measure: Change From Baseline in Nighttime maDBP and maSBP
timeFrame: baseline, 8 weeks
measure: Percentage of Participants Who Achieved a Successful Response in msDBP
timeFrame: 8 weeks
measure: Percentage of Participants Who Achieved a Successful Response in msSBP
timeFrame: 8 weeks
measure: Percentage of Participants Who Achieved Successful Control in msDBP
timeFrame: 8 weeks
measure: Percentage of Participants Who Achieved Successful Control in msSBP
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Muscle Shoals
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Chandler
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Buena Park
country: United States
facility: Novartis Investigative Site
state: California
city: Fair Oaks
country: United States
facility: Novartis Investigative Site
state: California
city: Long Beach
country: United States
facility: Novartis Investigative Site
state: California
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Orangevale
country: United States
facility: Novartis Investigative Site
state: California
city: Santa Ana
country: United States
facility: Novartis Investigative Site
state: California
city: Stockton
country: United States
facility: Novartis Investigative Site
state: California
city: Tustin
country: United States
facility: Novartis Investigative Site
state: California
city: Jacksonville
country: United States
facility: Novartis Investigative Site
state: Florida
city: Pembroke Pines
country: United States
facility: Novartis Investigative Site
state: Florida
city: Pembroke Pines
country: United States
facility: Novartis Investigative Site
state: Florida
city: Pensacola
country: United States
facility: Novartis Investigative Site
state: Florida
city: Augusta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Peoria
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Baton Rouge
country: United States
facility: Novartis Investigative Site
state: Louisiana
city: Metairie
country: United States
facility: Novartis Investigative Site
state: Louisiana
city: Chelsea
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Royal Oak
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Brooklyn Center
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: St. Peters
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Toms River
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Trenton
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Cincinnati
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Cincinnati
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Simpsonville
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Lake Jackson
country: United States
facility: Novartis Investigative Site
state: Texas
city: Richmond
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Charleston
country: United States
facility: Novartis Investigative Site
state: West Virginia
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Corrientes
country: Argentina
facility: Novartis Investigative Site
city: Cambridge
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Mississauga
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Granby
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Longueil
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Ste-Foy
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Saskatoon
country: Canada
facility: Novartis Investigative Site
state: Saskatchewan
city: Aalborg SV
country: Denmark
facility: Novartis Investigative Site
city: Aalborg
country: Denmark
facility: Novartis Investigative Site
city: Espergærde
country: Denmark
facility: Novartis Investigative Site
city: Greve
country: Denmark
facility: Novartis Investigative Site
city: Roslev
country: Denmark
facility: Novartis Investigative Site
city: Vaerloese
country: Denmark
facility: Novartis Investigative Site
city: Viborg
country: Denmark
facility: Novartis Investigative Site
city: Helsinki
country: Finland
facility: Novartis Investigative Site
city: Helsinki
country: Finland
facility: Novartis Investigative Site
city: Helsinki
country: Finland
facility: Novartis Investigative Site
city: Kerava
country: Finland
facility: Novartis Investigative Site
city: Oulu
country: Finland
facility: Novartis Investigative Site
city: Tampere
country: Finland
facility: Novartis Investigative Site
city: Bourges
country: France
facility: Novartis Investigative Site
city: La Chapelle sur Erdre
country: France
facility: Novartis Investigative Site
city: La Roche sur Yon
country: France
facility: Novartis Investigative Site
city: Le Pradet
country: France
facility: Novartis Investigative Site
city: Murs Erigné
country: France
facility: Novartis Investigative Site
city: Saint Avertin
country: France
facility: Novartis Investigative Site
city: Tours
country: France
facility: Novartis Investigative Site
city: Vihiers
country: France
facility: Novartis Investigative Site
city: Balve
country: Germany
facility: Novartis Investigative Site
city: Beckingen
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Einbeck
country: Germany
facility: Novartis Investigative Site
city: Erfurt
country: Germany
facility: Novartis Investigative Site
city: Giengen
country: Germany
facility: Novartis Investigative Site
city: Hagen
country: Germany
facility: Novartis Investigative Site
city: Haigerloch
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Kassel
country: Germany
facility: Novartis Investigative Site
city: Krefeld
country: Germany
facility: Novartis Investigative Site
city: Mahlberg
country: Germany
facility: Novartis Investigative Site
city: Messkirch
country: Germany
facility: Novartis Investigative Site
city: Reinfeld
country: Germany
facility: Novartis Investigative Site
city: Siegen
country: Germany
facility: Novartis Investigative Site
city: Wallerfing
country: Germany
facility: Novartis Investigative Site
city: Warendorf
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Esztergom
country: Hungary
facility: Novartis Investigative Site
city: Miskolc
country: Hungary
facility: Novartis Investigative Site
city: Nyiregyháza
country: Hungary
facility: Novartis Investigative Site
city: Caserta
country: Italy
facility: Novartis Investigative Site
state: CE
city: Cona
country: Italy
facility: Novartis Investigative Site
state: FE
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Pozzilli
country: Italy
facility: Novartis Investigative Site
state: IS
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Vimercate
country: Italy
facility: Novartis Investigative Site
state: MI
city: Palermo
country: Italy
facility: Novartis Investigative Site
state: PA
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Casorate Primo
country: Italy
facility: Novartis Investigative Site
state: PV
city: Pavia
country: Italy
facility: Novartis Investigative Site
state: PV
city: Stradella
country: Italy
facility: Novartis Investigative Site
state: PV
city: Mercato San Severino
country: Italy
facility: Novartis Investigative Site
state: SA
city: Sassari
country: Italy
facility: Novartis Investigative Site
state: SS
city: San Daniele Del Friuli
country: Italy
facility: Novartis Investigative Site
state: UD
city: Vibo Valentia
country: Italy
facility: Novartis Investigative Site
state: VV
city: Daugavplis
country: Latvia
facility: Novartis Investigative Site
city: Kuldiga
country: Latvia
facility: Novartis Investigative Site
city: Ogre
country: Latvia
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Alytus
country: Lithuania
facility: Novartis Investigative Site
city: Kaunas
country: Lithuania
facility: Novartis Investigative Site
city: Kaunas
country: Lithuania
facility: Novartis Investigative Site
city: Kaunas
country: Lithuania
facility: Novartis Investigative Site
city: Klaipeda
country: Lithuania
facility: Novartis Investigative Site
city: Den Bosch
country: Netherlands
facility: Novartis Investigative Site
city: Deurne
country: Netherlands
facility: Novartis Investigative Site
city: Ermelo
country: Netherlands
facility: Novartis Investigative Site
city: Hoogwoud
country: Netherlands
facility: Novartis Investigative Site
city: Leeuwarden
country: Netherlands
facility: Novartis Investigative Site
city: Losser
country: Netherlands
facility: Novartis Investigative Site
city: Oude Pekela
country: Netherlands
facility: Novartis Investigative Site
city: Poortvliet
country: Netherlands
facility: Novartis Investigative Site
city: Wamel
country: Netherlands
facility: Novartis Investigative Site
city: Olawa
country: Poland
facility: Novartis Investigative Site
city: Ostrow Wielkopolski
country: Poland
facility: Novartis Investigative Site
city: Tarnow
country: Poland
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: S.-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: S.-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Saint-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Saint-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Sankt-Peterburg
country: Russian Federation
facility: Novartis Investigative Site
city: Banska Bystrica
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Nitra
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Presov
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Dunajska Streda
country: Slovakia
facility: Novartis Investigative Site
city: Zilina
country: Slovakia
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Palma de Mallorca
country: Spain
facility: Novartis Investigative Site
state: Baleares
city: Badalona
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Tarrega
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Vic
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Alicante
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Benidorm
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Quart de Poblet
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Begonte
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Hospitalet de Llbregat
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Petrel
country: Spain
facility: Novartis Investigative Site
city: Riudecols
country: Spain
facility: Novartis Investigative Site
city: Arvidsjaur
country: Sweden
facility: Novartis Investigative Site
city: Boden
country: Sweden
facility: Novartis Investigative Site
city: Karlstad
country: Sweden
facility: Novartis Investigative Site
city: Kil
country: Sweden
facility: Novartis Investigative Site
city: Kristianstad
country: Sweden
facility: Novartis Investigative Site
city: Lund
country: Sweden
facility: Novartis Investigative Site
city: Skellefteå
country: Sweden
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan ROC
city: Tainan 704
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan ROC
city: Changhua
country: Taiwan
facility: Novartis Investigative Site
city: Taichung County
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_CHAIR
References:
citation: 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.
citation: Ruilope LM, Dukat A, Bohm M, Lacourciere Y, Gong J, Lefkowitz MP. Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study. Lancet. 2010 Apr 10;375(9722):1255-66. doi: 10.1016/S0140-6736(09)61966-8. Epub 2010 Mar 16.