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

NCT ID: NCT01692301

Last Updated: 2016-05-04

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

454 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-12-31

Study Completion Date

2015-04-30

Brief Summary

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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).

Detailed Description

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Conditions

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Hypertension

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 (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.

Group Type EXPERIMENTAL

LCZ696

Intervention Type DRUG

200 mg tablet

LCZ696 matching placebo

Intervention Type DRUG

LCZ696 Matching Placebo tablet

Olmesartan matching placebo

Intervention Type DRUG

Olmesartan matching placebo capsule

amlodipine

Intervention Type DRUG

amlodipine 2.5 mg or 5 mg tablets

hydrochlorothiazide

Intervention Type DRUG

hydrochlorothiazide 6.25mg, 12.5mg, or 25 mg tablets

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.

Group Type ACTIVE_COMPARATOR

Olmesartan

Intervention Type DRUG

20 mg and 40 mg capsules

LCZ696 matching placebo

Intervention Type DRUG

LCZ696 Matching Placebo tablet

amlodipine

Intervention Type DRUG

amlodipine 2.5 mg or 5 mg tablets

hydrochlorothiazide

Intervention Type DRUG

hydrochlorothiazide 6.25mg, 12.5mg, or 25 mg tablets

Interventions

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LCZ696

200 mg tablet

Intervention Type DRUG

Olmesartan

20 mg and 40 mg capsules

Intervention Type DRUG

LCZ696 matching placebo

LCZ696 Matching Placebo tablet

Intervention Type DRUG

Olmesartan matching placebo

Olmesartan matching placebo capsule

Intervention Type DRUG

amlodipine

amlodipine 2.5 mg or 5 mg tablets

Intervention Type DRUG

hydrochlorothiazide

hydrochlorothiazide 6.25mg, 12.5mg, or 25 mg tablets

Intervention Type DRUG

Other Intervention Names

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sacubitril/valsartan

Eligibility Criteria

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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.

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.
Minimum Eligible Age

60 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

Locations

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Novartis Investigative Site

Clearwater, Florida, United States

Site Status

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Chicago, Illinois, United States

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Baltimore, Maryland, United States

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Belzoni, Mississippi, United States

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Jackson, Mississippi, United States

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St Louis, Missouri, United States

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Buffalo, New York, United States

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Cincinnati, Ohio, United States

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Houston, Texas, United States

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Lake Jackson, Texas, United States

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Pasadena, Texas, United States

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Caba, Buenos Aires, Argentina

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Ramos Mejía, Buenos Aires, Argentina

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Rosario, Santa Fe Province, Argentina

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Barranquilla, Atlántico, Colombia

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Barranquilla, , Colombia

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Paris, , France

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Berlin, , Germany

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Nuremberg, , Germany

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Athens, Athens, Greece

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Athens, Athens, Greece

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Thessaloniki, Greece, Greece

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Treviglio, BG, Italy

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Pisa, PI, Italy

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San Daniele del Friuli, UD, Italy

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Shimotsuke, Tochigi, Japan

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Yaroslavl, , Russia

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Bucheon-si, Gyeonggi-do, South Korea

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Seoul, Korea, South Korea

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Seville, Andalusia, Spain

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Jerez de la Frontera, Cadiz, Spain

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Barcelona, Catalonia, Spain

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Barcelona, Catalonia, Spain

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Centelles, Catalonia, Spain

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Terrassa, Catalonia, Spain

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A Coruña, Galicia, Spain

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Madrid, Madrid, Spain

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Madrid, Madrid, Spain

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Port de Sagunt, Valencia, Spain

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Taichung, Taiwan, Taiwan

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Taipei, Taiwan, Taiwan

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Novartis Investigative Site

Taipei, Taiwan, ROC, Taiwan

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Countries

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United States Argentina Colombia France Germany Greece Italy Japan Russia South Korea Spain Taiwan

References

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Williams B, Cockcroft JR, Kario K, Zappe DH, Cardenas P, Hester A, Brunel P, Zhang J. Rationale and study design of the Prospective comparison of Angiotensin Receptor neprilysin inhibitor with Angiotensin receptor blocker MEasuring arterial sTiffness in the eldERly (PARAMETER) study. BMJ Open. 2014 Feb 4;4(2):e004254. doi: 10.1136/bmjopen-2013-004254.

Reference Type DERIVED
PMID: 24496699 (View on PubMed)

Other Identifiers

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2012-002899-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLCZ696A2216

Identifier Type: -

Identifier Source: org_study_id

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