Эта страница была переведена автоматически, точность перевода не гарантируется. Пожалуйста, обратитесь к английской версии для исходного текста.

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

12 августа 2015 г. обновлено: Novartis Pharmaceuticals

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.

Обзор исследования

Статус

Завершенный

Условия

Вмешательство/лечение

Тип исследования

Интервенционный

Регистрация (Действительный)

307

Фаза

  • Фаза 2

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Места учебы

  • Аргентина
      • Cordoba, Аргентина, X5000EVQ
        • Novartis Investigative Site
      • Cordoba, Аргентина, X5000EPU
        • Novartis Investigative Site
      • Corrientes, Аргентина, W3400
        • Novartis Investigative Site
      • Santa Fe, Аргентина, 3000
        • Novartis Investigative Site
      • Santa Fe, Аргентина, S3000FWO
        • Novartis Investigative Site
    • Buenos Aires
      • Caba, Buenos Aires, Аргентина, C1408INH
        • Novartis Investigative Site
      • Ciudad Autonoma de Bs As, Buenos Aires, Аргентина, C1119ACN
        • Novartis Investigative Site
      • Ramos Mejia, Buenos Aires, Аргентина, B1704ETD
        • Novartis Investigative Site
      • San Martin, Buenos Aires, Аргентина, B1650CSQ
        • Novartis Investigative Site
    • Santa Fe
      • Rosario, Santa Fe, Аргентина, S200CVD
        • Novartis Investigative Site
    • Tucuman
      • San Miguel de Tucuman, Tucuman, Аргентина, T4000EBR
        • Novartis Investigative Site
  • Бразилия
    • GO
      • Goiania, GO, Бразилия, 74605-050
        • Novartis Investigative Site
    • RS
      • Porto Alegre, RS, Бразилия, 90610-000
        • Novartis Investigative Site
    • SP
      • Sao Jose do Rio Preto, SP, Бразилия, 15015-750
        • Novartis Investigative Site
      • São Paulo, SP, Бразилия, 05403-000
        • Novartis Investigative Site
  • Венесуэла
    • Distrito Capital
      • Caracas, Distrito Capital, Венесуэла, 1010
        • Novartis Investigative Site
    • Estado Zulia
      • Maracaibo, Estado Zulia, Венесуэла, 4011
        • Novartis Investigative Site
  • Германия
      • Göttingen, Германия, D-37075
        • Novartis Investigative Site
  • Индия
      • Hyderabad, Индия, 500 063
        • Novartis Investigative Site
    • Andhra Pradesh
      • Hyderabad, Andhra Pradesh, Индия, 500012
        • Novartis Investigative Site
    • Andhra Pradesh, INDIA
      • Hyderabad, Andhra Pradesh, INDIA, Индия, 500034
        • Novartis Investigative Site
    • Delhi
      • New Delhi, Delhi, Индия, 110060
        • Novartis Investigative Site
    • Karnataka
      • Mangalore, Karnataka, Индия, 575002
        • Novartis Investigative Site
      • Manipal, Karnataka, Индия, 576104
        • Novartis Investigative Site
    • Maharashtra
      • Mumbai, Maharashtra, Индия, 400 022
        • Novartis Investigative Site
      • Nagpur, Maharashtra, Индия, 440012
        • Novartis Investigative Site
      • Nagpur, Maharashtra, Индия, 44000033
        • Novartis Investigative Site
    • Rajasthan
      • Jaipur, Rajasthan, Индия, 302004
        • Novartis Investigative Site
      • Jaipur, Rajasthan, Индия, 302001
        • Novartis Investigative Site
  • Испания
      • Madrid, Испания, 28034
        • Novartis Investigative Site
      • Madrid, Испания, 28046
        • Novartis Investigative Site
    • Andalucia
      • Sevilla, Andalucia, Испания, 41009
        • Novartis Investigative Site
    • Barcelona
      • Hospitalet de Llobregat, Barcelona, Испания, 08907
        • Novartis Investigative Site
    • Comunidad Valenciana
      • Alicante, Comunidad Valenciana, Испания, 03004
        • Novartis Investigative Site
    • Galicia
      • A Coruna, Galicia, Испания, 15006
        • Novartis Investigative Site
      • Santiago de Compostela, Galicia, Испания, 15706
        • Novartis Investigative Site
  • Италия
    • BG
      • Bergamo, BG, Италия, 24128
        • Novartis Investigative Site
    • CS
      • Cosenza, CS, Италия, 87100
        • Novartis Investigative Site
    • PI
      • Pisa, PI, Италия, 56124
        • Novartis Investigative Site
    • PV
      • Casorate Primo, PV, Италия, 27022
        • Novartis Investigative Site
    • SP
      • Sarzana, SP, Италия, 19038
        • Novartis Investigative Site
    • UD
      • San Daniele Del Friuli, UD, Италия, 33038
        • Novartis Investigative Site
    • VA
      • Somma Lombardo, VA, Италия, 21019
        • Novartis Investigative Site
  • Канада
    • Ontario
      • Brampton, Ontario, Канада, L6Z 4N5
        • Novartis Investigative Site
    • Quebec
      • Montreal, Quebec, Канада, H3G 1A4
        • Novartis Investigative Site
      • Montreal, Quebec, Канада, H3A 1A1
        • Novartis Investigative Site
  • Нидерланды
      • Amsterdam, Нидерланды, 1105 AZ
        • Novartis Investigative Site
      • Delft, Нидерланды, NL 2625 AD
        • Novartis Investigative Site
      • Ede, Нидерланды, 6716 RP
        • Novartis Investigative Site
      • Goes, Нидерланды, 4462 RA
        • Novartis Investigative Site
      • Groningen, Нидерланды, 9713 GZ
        • Novartis Investigative Site
      • Heerenveen, Нидерланды, 8441 PW
        • Novartis Investigative Site
      • Heerlen, Нидерланды, 6419 PC
        • Novartis Investigative Site
      • Hengelo, Нидерланды, 7555 DL
        • Novartis Investigative Site
  • Польша
      • Piotrkow Trybunalski, Польша, 97-300
        • Novartis Investigative Site
      • Sieradz, Польша, 98-200
        • Novartis Investigative Site
      • Warszawa/Anin, Польша, 04-761
        • Novartis Investigative Site
      • Wroclaw, Польша, 51-124
        • Novartis Investigative Site
      • Wroclaw, Польша, 50-981
        • Novartis Investigative Site
  • Российская Федерация
      • Moscow, Российская Федерация, 117292
        • Novartis Investigative Site
      • Moscow, Российская Федерация, 121552
        • Novartis Investigative Site
      • S.-Petersburg, Российская Федерация, 196247
        • Novartis Investigative Site
      • Saint-Petersburg, Российская Федерация, 194044
        • Novartis Investigative Site
      • Saint-Petersburg, Российская Федерация, 197341
        • Novartis Investigative Site
  • Румыния
      • Baia Mare, Румыния, 430031
        • Novartis Investigative Site
      • Pitesti, Румыния, 110114
        • Novartis Investigative Site
    • Jud. Dolj
      • Craiova, Jud. Dolj, Румыния, 200147
        • Novartis Investigative Site
    • Jud.Dolj
      • Craiova, Jud.Dolj, Румыния, 200235
        • Novartis Investigative Site
  • Сингапур
      • Singapore, Сингапур, 119074
        • Novartis Investigative Site
      • Singapore, Сингапур, 169609
        • Novartis Investigative Site
  • Соединенные Штаты
    • Arkansas
      • Little Rock, Arkansas, Соединенные Штаты, 72205
        • Novartis Investigative Site
    • Illinois
      • Chicago, Illinois, Соединенные Штаты, 60657
        • Novartis Investigative Site
    • Michigan
      • Detroit, Michigan, Соединенные Штаты, 48201
        • Novartis Investigative Site
    • Nebraska
      • Grand Island, Nebraska, Соединенные Штаты, 68803
        • Novartis Investigative Site
      • Lincoln, Nebraska, Соединенные Штаты, 68506
        • Novartis Investigative Site
    • Oklahoma
      • Oklahoma City, Oklahoma, Соединенные Штаты, 73120
        • Novartis Investigative Site
      • Tulsa, Oklahoma, Соединенные Штаты, 74133
        • Novartis Investigative Site
    • Oregon
      • Hillsboro, Oregon, Соединенные Штаты, 97123
        • Novartis Investigative Site
    • Pennsylvania
      • Wyomissing, Pennsylvania, Соединенные Штаты, 19610
        • Novartis Investigative Site
    • Tennessee
      • Nashville, Tennessee, Соединенные Штаты, 37203
        • Novartis Investigative Site
    • Texas
      • Houston, Texas, Соединенные Штаты, 77025
        • Novartis Investigative Site

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

40 лет и старше (Взрослый, Пожилой взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Все

Описание

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

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Рандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Двойной

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Экспериментальный: 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.
Лекарство: LCZ696
50 mg, 100 mg and 200 mg tablets
Лекарство: Placebo
matching placebo to LCZ696 and Valsartan
Активный компаратор: 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.
Лекарство: Placebo
matching placebo to LCZ696 and Valsartan
Лекарство: Valsartan
40 mg, 80 mg and 160 mg tablets

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)
Временное ограничение: Baseline, 12 weeks
Evaluation of NT-proBNP was performed by a central laboratory. Change from baseline in NT-proBNP was presented as a ratio where the ratio was calculated as the NT-proBNP value at 12 weeks over the NT-proBNP value at baseline. A ratio < 1 indicates improvement.
Baseline, 12 weeks

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Change From Baseline in NT-proBNP and Brain Natriuretic Peptide (BNP)
Временное ограничение: baseline, 36 weeks
Evaluation of NT-proBNP and BNP was performed by a central laboratory. Change from baseline in NT-proBNP and in BNP was presented as a ratio where the ratio for NT-proBNP was calculated as the NT-proBNP value at 36 weeks over the NT-proBNP value at baseline, and the ratio for BNP was calculated as the BNP value at 36 weeks over the BNP value at baseline. A ratio < 1 indicates improvement.
baseline, 36 weeks
Change From Baseline in Plasma Cyclic Guanine Monophosphate (cGMP)
Временное ограничение: baseline, 36 weeks
Evaluation of cGMP was performed by a central laboratory. Change from baseline in cGMP was presented as a ratio where the ratio was calculated as the cGMP value at 36 weeks over the cGMP value at baseline. A ratio < 1 indicates improvement.
baseline, 36 weeks
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
Временное ограничение: Baseline, 36 weeks
A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Baseline, 36 weeks
Change From Baseline in Echocardiography Parameters: LVE Diastolic Volume, LVE Systolic Volume, Left Ventricular Stroke Volume, Left Atrial Volume
Временное ограничение: Baseline, 36 weeks
A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Baseline, 36 weeks
Change From Baseline in Echocardiography Parameters: Left Ventricular Ejection Fraction
Временное ограничение: Baseline, 36 weeks
A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Baseline, 36 weeks
Change From Baseline in Echocardiography Parameters: Left Ventricular Mass
Временное ограничение: Baseline, 36 weeks
A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Baseline, 36 weeks
Change From Baseline in Echocardiography Parameters: Left Ventricular Mass Index
Временное ограничение: Baseline, 36 weeks
A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Baseline, 36 weeks
Change From Baseline in Echocardiography Parameters: Left Atrial Volume Index
Временное ограничение: Baseline, 36 weeks
A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Baseline, 36 weeks
Change From Baseline in Echocardiography Parameters: Ewave Velocity, A Wave Velocity, e' at Septal Mitral Annulus, e' at Lateral Mitral Annulus
Временное ограничение: Baseline, 36 weeks
A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Baseline, 36 weeks
Change From Baseline in Echocardiography Parameters: Ratio of E to A Velocity, E/e' Ratio
Временное ограничение: Baseline, 36 weeks
A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A ratio < 1 indicates improvement.
Baseline, 36 weeks
Change in Echocardiography Parameters: Isovolumic Relaxation Time
Временное ограничение: Baseline, 36 weeks
A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Baseline, 36 weeks
Change From Baseline in Echocardiography Parameters: Tricuspid Regurgitation Velocity
Временное ограничение: Baseline, 36 weeks
A limited two-dimensional and Doppler ECHO examination was done to assess ECHO parameters. A negative change from baseline indicates improvement.
Baseline, 36 weeks
Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score and Individual Domain Summary Scores
Временное ограничение: baseline, 36 weeks
The KCCQ is a self-administered questionnaire. It contains 23 items, covering physical function, clinical symptoms, social function, self-efficacy and knowledge, and quality of life, each with different Likert scale wording, including limitations, frequency, bother, change in condition, understanding, levels of enjoyment and satisfaction. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. A positive change from baseline indicates improvement.
baseline, 36 weeks
Percentage of Participants With Clinical Composite Assessment of Improved, Unchanged or Worsened
Временное ограничение: 36 weeks
The clinical composite assessment is defined as follows: Improved = a) participant improved (markedly or moderately) in the global assessment of disease activity with no worsening of NYHA functional class and no major adverse cardiovascular event or b) participant improved in NYHA functional class with no worsening (markedly or moderately) in the global assessment of disease activity and no major adverse cardiovascular event. Worsened = participant worsened (markedly or moderately) in the global assessment of disease activity or in NYHA functional class or experienced a major adverse cardiovascular event. Unchanged = participant does not meet the definition for improved or worsened.
36 weeks
Percentage of Participants With New York Heart Association (NYHA) Class I, II, II or IV
Временное ограничение: baseline, 36 weeks
The NYHA Functional Classification classifies patients' heart failure according to the severity of their symptoms. The classification is as follows: Class I: no limitation of physical activity, ordinary physical activity does not cause undue fatigue, palpitation, or dyspnea (shortness of breath); Class II: slight limitation to physical activity, comfortable at rest, ordinary physical activity results in fatigue, palpitation or dyspnea; Class III: marked limitation of physical activity, comfortable at rest, less than ordinary activity causes fatigue, palpitation or dyspnea; Class IV: unable to carry on any physical activity without discomfort, symptoms of heart failure at rest, if any physical activity is undertaken, discomfort increases.
baseline, 36 weeks
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Временное ограничение: baseline, 36 weeks
eGFR was calculated from the serum creatinine concentration determined by central laboratory assessment. A positive change from baseline indicates improvement.
baseline, 36 weeks
Change From Baseline in Serum Creatinine
Временное ограничение: baseline, 36 weeks
Evaluation of serum creatinine was performed by central laboratory. A negative change from baseline indicates improvement.
baseline, 36 weeks
Change From Baseline in Albumin/Creatinine Ratio
Временное ограничение: baseline, 36 weeks
Evaluation of albumin/creatinine was performed by central laboratory. A ratio < 1 indicates improvement.
baseline, 36 weeks
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
Временное ограничение: baseline, 36 weeks
A vascular arterial stiffness sub-study was conducted in a subset of participants. Noninvasive arterial tonometry was assessed using the Sphygmor device. Participants had arterial stiffness, pulse wave velocity and central pressures measured. A negative change from baseline indicates improvement.
baseline, 36 weeks
Change From Baseline in Arterial Stiffness Parameters: Heart Rate Correct Cen Aug/Pulse Ht
Временное ограничение: baseline, 36 weeks
A vascular arterial stiffness sub-study was conducted in a subset of participants. Noninvasive arterial tonometry was assessed using the Sphygmor device. Participants had arterial stiffness, pulse wave velocity and central pressures measured. A negative change from baseline indicates improvement.
baseline, 36 weeks
Change From Baseline in Arterial Stiffness Parameters: Heart Rate
Временное ограничение: baseline, 36 weeks
A vascular arterial stiffness sub-study was conducted in a subset of participants. Noninvasive arterial tonometry was assessed using the Sphygmor device. Participants had arterial stiffness, pulse wave velocity and central pressures measured. A negative change from baseline indicates improvement.
baseline, 36 weeks
Change From Baseline in Arterial Stiffness Parameters: Pulse Wave Velocity
Временное ограничение: baseline, 36 weeks
A vascular arterial stiffness sub-study was conducted in a subset of participants. Noninvasive arterial tonometry was assessed using the Sphygmor device. Participants had arterial stiffness, pulse wave velocity and central pressures measured. A negative change from baseline indicates improvement.
baseline, 36 weeks
Change From Baseline in Sitting SBP, Sitting DBP and Sitting Pulse Pressure (PP)
Временное ограничение: baseline, 36 weeks
Sitting blood pressure and sitting pulse pressure were assessed. A negative change from baseline indicates improvement.
baseline, 36 weeks

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

Novartis Pharmaceuticals

Публикации и полезные ссылки

Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.

Общие публикации

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования

1 ноября 2009 г.

Первичное завершение (Действительный)

1 декабря 2011 г.

Завершение исследования (Действительный)

1 декабря 2011 г.

Даты регистрации исследования

Первый отправленный

22 апреля 2009 г.

Впервые представлено, что соответствует критериям контроля качества

23 апреля 2009 г.

Первый опубликованный (Оценивать)

24 апреля 2009 г.

Обновления учебных записей

Последнее опубликованное обновление (Оценивать)

25 августа 2015 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

12 августа 2015 г.

Последняя проверка

1 августа 2015 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • CLCZ696B2214
  • 2009-010208-27

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

Клинические исследования Хроническая сердечная недостаточность

Клинические исследования LCZ696

Искать похожие исследования

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

CROs by country

CROs in Saint Lucia

Заболевания

Редкие заболевания

Медикаментозные вмешательства

Пищевые добавки

Спонсор / Соавторы

Места

Подписаться