Study of the Safety and Efficacy of LCZ696 on Arterial Stiffness in Elderly Patients With Hypertension

March 31, 2016 updated by: Novartis Pharmaceuticals

A Randomized, Double-blind 52-week Study to Evaluate the Safety and Efficacy of an LCZ696 Regimen Compared to an Olmesartan Regimen on Arterial Stiffness Through Assessment of Central Blood Pressure in Elderly Patients With Hypertension

The study examined the efficacy of LCZ696 in comparison to the ARB olmesartan on Central Aortic Systolic Blood Pressure (CASP) and other measures of central hemodynamics and arterial stiffness in elderly patients with an elevated systolic blood pressure (SBP) and widened pulse pressure (PP).

Study Overview

Study Type

Interventional

Enrollment (Actual)

454

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Buenos Aires
      • Caba, Buenos Aires, Argentina, C1440AAD
        • Novartis Investigative Site
      • Ramos Mejia, Buenos Aires, Argentina, B1704ETD
        • Novartis Investigative Site
    • Santa Fe
      • Rosario, Santa Fe, Argentina, S2000CXH
        • Novartis Investigative Site
      • Barranquilla, Colombia
        • Novartis Investigative Site
    • Atlantico
      • Barranquilla, Atlantico, Colombia
        • Novartis Investigative Site
      • Paris, France, 75015
        • Novartis Investigative Site
      • Berlin, Germany, 10117
        • Novartis Investigative Site
      • Nuernberg, Germany, 90471
        • Novartis Investigative Site
      • Athens, Greece, 11526
        • Novartis Investigative Site
      • Athens, Greece, 11525
        • Novartis Investigative Site
      • Thessaloniki, Greece, 54642
        • Novartis Investigative Site
    • BG
      • Treviglio, BG, Italy, 24047
        • Novartis Investigative Site
    • PI
      • Pisa, PI, Italy, 56126
        • Novartis Investigative Site
    • UD
      • San Daniele Del Friuli, UD, Italy, 33038
        • Novartis Investigative Site
    • Tochigi
      • Shimotsuke-city, Tochigi, Japan, 329-0498
        • Novartis Investigative Site
    • Gyeonggi-do
      • Bucheon, Gyeonggi-do, Korea, Republic of, 424-717
        • Novartis Investigative Site
    • Korea
      • Seoul, Korea, Korea, Republic of, 110 744
        • Novartis Investigative Site
      • Moscow, Russian Federation, 117198
        • Novartis Investigative Site
      • Moscow, Russian Federation, 119992
        • Novartis Investigative Site
      • Moscow, Russian Federation, 101990
        • Novartis Investigative Site
      • Saint Petersburg, Russian Federation, 197022
        • Novartis Investigative Site
      • Saint-Petersburg, Russian Federation, 197341
        • Novartis Investigative Site
      • Yaroslavl, Russian Federation, 150047
        • Novartis Investigative Site
      • Madrid, Spain, 28041
        • Novartis Investigative Site
      • Madrid, Spain, 28034
        • Novartis Investigative Site
    • Andalucia
      • Sevilla, Andalucia, Spain, 41071
        • Novartis Investigative Site
    • Cadiz
      • Jerez de La Frontera, Cadiz, Spain, 11407
        • Novartis Investigative Site
    • Cataluna
      • Barcelona, Cataluna, Spain, 08003
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08025
        • Novartis Investigative Site
      • Terrassa, Catalunya, Spain, 08221
        • Novartis Investigative Site
    • Cataluña
      • Centelles, Cataluña, Spain, 08540
        • Novartis Investigative Site
    • Comunidad Valenciana
      • Puerto de Sagunto, Comunidad Valenciana, Spain, 46520
        • Novartis Investigative Site
    • Galicia
      • La Coruna, Galicia, Spain, 15706
        • Novartis Investigative Site
      • Taichung, Taiwan, 40447
        • Novartis Investigative Site
      • Taipei, Taiwan, 114
        • Novartis Investigative Site
    • Taiwan, ROC
      • Taipei, Taiwan, ROC, Taiwan, 112
        • Novartis Investigative Site
    • Florida
      • Clearwater, Florida, United States, 33756
        • Novartis Investigative Site
    • Illinois
      • Chicago, Illinois, United States, 60607
        • Novartis Investigative Site
    • Maryland
      • Baltimore, Maryland, United States, 21204
        • Novartis Investigative Site
    • Mississippi
      • Belzoni, Mississippi, United States, 39038
        • Novartis Investigative Site
      • Jackson, Mississippi, United States, 39209
        • Novartis Investigative Site
    • Missouri
      • St. Louis, Missouri, United States, 63141
        • Novartis Investigative Site
    • New York
      • Buffalo, New York, United States, 14215
        • Novartis Investigative Site
    • Ohio
      • Cincinnati, Ohio, United States, 45224
        • Novartis Investigative Site
    • Texas
      • Houston, Texas, United States, 77081
        • Novartis Investigative Site
      • Lake Jackson, Texas, United States, 77566
        • Novartis Investigative Site
      • Pasadena, Texas, United States, 77504
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  1. Male and female patients ≥ 60 years of age.
  2. Patients with essential hypertension, untreated or currently taking antihypertensive therapy.
  3. Untreated patients must have an office msSBP ≥150 mmHg and <180 mmHg at Visit 101 and Visit 201 if they are newly diagnosed or have not been treated with antihypertensive drugs for the 4 weeks prior to Visit 1.
  4. Treated patients must have an office msSBP ≥140 mmHg and <180 mmHg at Visit 102 (or Visit 103) and msSBP ≥150 mmHg and <180 mmHg at Visit 201 if they have been treated with antihypertensive drugs for the 4 weeks prior to Visit 1.
  5. All patients must have pulse pressure >60 mmHg at Visit 201. Pulse pressure is defined as msSBP- msDBP.
  6. Patients must have a difference in msSBP within +/-15 mmHg between Visit 201 (randomization) and the visit immediately prior to Visit 201.

Key Exclusion Criteria:

  1. Malignant or severe hypertension (grade 3 of WHO classification; msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg)
  2. History of angioedema, drug-related or otherwise.
  3. History or evidence of a secondary form of hypertension, including but not limited to any of the following: renal parenchymal hypertension, renovascular hypertension (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, polycystic kidney disease, and drug-induced hypertension.
  4. Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any history of stroke.
  5. History of myocardial infarction, coronary bypass surgery or any percutaneous coronary intervention (PCI) during the 12 months prior to Visit 1.
  6. History of atrial fibrillation or atrial flutter during the 3 months prior to Visit 1, or active atrial fibrillation or atrial flutter on the ECG at screening.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: LCZ696 (sacubitril/valsartan)
Randomized patients received LCZ696 once daily for four weeks, then they force-titrated to a higher dose at Week 4 and stayed on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696, its matching placebo) and 1 capsule (olmesartan matching placebo) were given during the entire study.
200 mg tablet
Other Names:
  • sacubitril/valsartan
LCZ696 Matching Placebo tablet
Olmesartan matching placebo capsule
amlodipine 2.5 mg or 5 mg tablets
hydrochlorothiazide 6.25mg, 12.5mg, or 25 mg tablets
ACTIVE_COMPARATOR: Olmesartan
Randomized patients received olmesartan once daily for four weeks, then force-titrated to a higher dose at Week 4 and stayed on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP allowed to have amlodipine then hydrochlorothiazide (HCTZ) added at intervals of 4 weeks from Week 12 up to Week 24. To maintain the double dummy, double-blind design, 2 tablets (LCZ696 matching placebo) and 1 capsule (olmesartan) were given during the entire study.
LCZ696 Matching Placebo tablet
amlodipine 2.5 mg or 5 mg tablets
hydrochlorothiazide 6.25mg, 12.5mg, or 25 mg tablets
20 mg and 40 mg capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 12 Weeks
Time Frame: baseline, 12 weeks

Central aortic blood pressure was derived from peripheral pressure waveforms recorded noninvasively from the brachial artery using a cuff-based device. This technique uses the brachial pressure and a signal processing algorithm to transform brachial signals into central blood pressure (BP) waveforms. When the aortic pressure waveform was derived, key pulse wave analysis (PWA) parameters, such as CASP was calculated by the system software.

At the first study visit, the arm with the highest systolic blood pressure (SBP) was used for all subsequent PWA. Brachial PWA measurements were performed on the same arm that the office blood pressures were taken. Two pulse waveform measurements, meeting all quality control criteria were captured at baseline and at week 12 visits.

baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Mean Central Pulse (CPP) Pressure
Time Frame: Baseline, 12 weeks, and 52 weeks
Baseline, 12 weeks, and 52 weeks
Change From Baseline in Mean Pulse Wave Velocity (PWV)
Time Frame: baseline, 12 weeks, and 52 weeks

Pulse wave velocity recordings were performed on patient while in a supine, face-up position.

Tonometry was performed on the carotid simultaneously with the cuff inflation over the femoral artery. Two pulse wave velocity measures, meeting all quality control criteria were captured at baseline, week 12 and week 52.

baseline, 12 weeks, and 52 weeks
Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 52 Weeks
Time Frame: baseline, 52 weeks

Central aortic blood pressure was derived from peripheral pressure waveforms recorded noninvasively from the brachial artery using a cuff-based device. This technique uses the brachial pressure and a signal processing algorithm to transform brachial signals into central blood pressure (BP) waveforms. When the aortic pressure waveform was derived, key pulse wave analysis (PWA) parameters, such as CASP was calculated by the system software.

At the first study visit, the arm with the highest systolic blood pressure (SBP) was used for all subsequent PWA. Brachial PWA measurements were performed on the same arm that the office blood pressures were taken. Two pulse waveform measurements, meeting all quality control criteria were captured at baseline and at week 12 visits.

baseline, 52 weeks
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)
Time Frame: baseline, 12 weeks, and 52 weeks
At the first study visit, the patient had his/her blood pressure (BP) measured in both arms; the arm in which the highest sitting SBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, SBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.
baseline, 12 weeks, and 52 weeks
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)
Time Frame: baseline, 12 weeks, and 52 weeks
At the first study visit, the patient had his/her blood pressure (BP) measured in both arms; the arm in which the highest sitting SBP was found was used for all subsequent readings throughout the study. At each study visit, after the patient had been sitting for 5 minutes, DBP were measured 3 times using a standard mercury sphygmomanometer and appropriate size cuff. The repeat sitting measurements were made at 1- to 2-minute intervals and the mean of those 3 measurements was used as the average sitting office BP for that visit.
baseline, 12 weeks, and 52 weeks
Change From Baseline in Mean Sitting Pulse Pressure (msPP)
Time Frame: baseline, 12 weeks, and 52 weeks
Mean sitting pulse pressure for each patient and visit was calculated as the difference between the calculated values of mean sitting systolic blood pressure and mean sitting diastolic blood pressure.
baseline, 12 weeks, and 52 weeks
Change From Baseline in Mean Arterial Pressure (MAP)
Time Frame: baseline, 12 weeks, and 52 weeks
Mean arterial pressure (MAP) was calculated from mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) as (2 * msDBP + msSBP)/3.
baseline, 12 weeks, and 52 weeks
Change From Baseline in Mean 24-hour Systolic Blood Pressure (maSBP)
Time Frame: Baseline, 12 weeks, and 52 weeks
An Ambulatory Blood Pressure Monitor (ABPM) measured a participant's blood pressure over a 24 hour period using an automated validated monitoring device at baseline, week 12 and at week 52 starting one day before each visit. The 24 hour maSBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24 hour period.
Baseline, 12 weeks, and 52 weeks
Change From Baseline in Mean 24-hour Diastolic Blood Pressure (maDBP)
Time Frame: Baseline, 12 weeks, and 52 weeks
An Ambulatory Blood Pressure Monitor (ABPM) measured a participant's blood pressure over a 24 hour period using an automated validated monitoring device at baseline, week 12 and at week 52 starting one day before each visit. The 24 hour maDBP was calculated by taking the mean of all ambulatory systolic blood pressure readings for the 24 hour period.
Baseline, 12 weeks, and 52 weeks
Change From Baseline in Mean 24-hour Ambulatory Pulse Pressure (maPP)
Time Frame: Baseline, 12 weeks, and 52 weeks
Mean 24 hour ambulatory pulse pressure was calculated as the difference between the mean 24 hour systolic and diastolic ambulatory blood pressure in corresponding visits i.e. baseline, week 12 and week 52.
Baseline, 12 weeks, and 52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2012

Primary Completion (ACTUAL)

April 1, 2015

Study Completion (ACTUAL)

April 1, 2015

Study Registration Dates

First Submitted

September 20, 2012

First Submitted That Met QC Criteria

September 20, 2012

First Posted (ESTIMATE)

September 25, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

May 4, 2016

Last Update Submitted That Met QC Criteria

March 31, 2016

Last Verified

March 1, 2016

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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