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

NCT01692301 | Completed Phase 2 Results DMC

• 2 other identifiers: CLCZ696A22162012-002899-14
• Study Type: interventional
• Target: 454
• Locations: 12 countries
• Sites: 47

Brief Summary

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).

Conditions

Hypertension

Keywords

hypertension, elderly, central aortic pulse pressure, central pulse pressure, pulse wave velocity

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 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 Outcomes (10)

• Change From Baseline in Mean Central Pulse (CPP) Pressure

  Baseline, 12 weeks, and 52 weeks

• Change From Baseline in Mean Pulse Wave Velocity (PWV)

  baseline, 12 weeks, and 52 weeks

• Change From Baseline in Mean Central Aortic Systolic Pressure (CASP) at 52 Weeks

  baseline, 52 weeks

• Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP)

  baseline, 12 weeks, and 52 weeks

• Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP)

  baseline, 12 weeks, and 52 weeks

Study Arms (2)

LCZ696 (sacubitril/valsartan)

EXPERIMENTAL

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.

Drug: LCZ696; Drug: LCZ696 matching placebo; Drug: Olmesartan matching placebo; Drug: amlodipine; Drug: hydrochlorothiazide

Olmesartan

ACTIVE COMPARATOR

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.

Drug: Olmesartan; Drug: LCZ696 matching placebo; Drug: amlodipine; Drug: hydrochlorothiazide

Interventions

LCZ696 DRUG

200 mg tablet

Also known as: sacubitril/valsartan

LCZ696 (sacubitril/valsartan)

Olmesartan DRUG

20 mg and 40 mg capsules

Olmesartan

LCZ696 matching placebo DRUG

LCZ696 Matching Placebo tablet

LCZ696 (sacubitril/valsartan); Olmesartan

Olmesartan matching placebo DRUG

Olmesartan matching placebo capsule

LCZ696 (sacubitril/valsartan)

amlodipine DRUG

amlodipine 2.5 mg or 5 mg tablets

LCZ696 (sacubitril/valsartan); Olmesartan

hydrochlorothiazide DRUG

hydrochlorothiazide 6.25mg, 12.5mg, or 25 mg tablets

LCZ696 (sacubitril/valsartan); Olmesartan

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients ≥ 60 years of age.
• Patients with essential hypertension, untreated or currently taking antihypertensive therapy.
• 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.
• 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.
• All patients must have pulse pressure \>60 mmHg at Visit 201. Pulse pressure is defined as msSBP- msDBP.
• Patients must have a difference in msSBP within +/-15 mmHg between Visit 201 (randomization) and the visit immediately prior to Visit 201.

You may not qualify if:

• Malignant or severe hypertension (grade 3 of WHO classification; msDBP ≥110 mmHg and/or msSBP ≥ 180 mmHg)
• History of angioedema, drug-related or otherwise.
• 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.
• Transient ischemic cerebral attack (TIA) during the 12 months prior to Visit 1 or any history of stroke.
• History of myocardial infarction, coronary bypass surgery or any percutaneous coronary intervention (PCI) during the 12 months prior to Visit 1.
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (47)

Novartis Investigative Site

Clearwater, Florida, 33756, United States

Location

Novartis Investigative Site

Chicago, Illinois, 60607, United States

Location

Novartis Investigative Site

Baltimore, Maryland, 21204, United States

Location

Novartis Investigative Site

Belzoni, Mississippi, 39038, United States

Location

Novartis Investigative Site

Jackson, Mississippi, 39209, United States

Location

Novartis Investigative Site

St Louis, Missouri, 63141, United States

Location

Novartis Investigative Site

Buffalo, New York, 14215, United States

Location

Novartis Investigative Site

Cincinnati, Ohio, 45224, United States

Location

Novartis Investigative Site

Houston, Texas, 77081, United States

Location

Novartis Investigative Site

Lake Jackson, Texas, 77566, United States

Location

Novartis Investigative Site

Pasadena, Texas, 77504, United States

Location

Novartis Investigative Site

Caba, Buenos Aires, C1440AAD, Argentina

Location

Novartis Investigative Site

Ramos Mejía, Buenos Aires, B1704ETD, Argentina

Location

Novartis Investigative Site

Rosario, Santa Fe Province, S2000CXH, Argentina

Location

Novartis Investigative Site

Barranquilla, Atlántico, Colombia

Location

Novartis Investigative Site

Barranquilla, Colombia

Location

Novartis Investigative Site

Paris, 75015, France

Location

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Nuremberg, 90471, Germany

Location

Novartis Investigative Site

Athens, Athens, 11525, Greece

Location

Novartis Investigative Site

Athens, Athens, 11526, Greece

Location

Novartis Investigative Site

Thessaloniki, Greece, 54642, Greece

Location

Novartis Investigative Site

Treviglio, BG, 24047, Italy

Location

Novartis Investigative Site

Pisa, PI, 56126, Italy

Location

Novartis Investigative Site

San Daniele del Friuli, UD, 33038, Italy

Location

Novartis Investigative Site

Shimotsuke, Tochigi, 329-0498, Japan

Location

Novartis Investigative Site

Moscow, 101990, Russia

Location

Novartis Investigative Site

Moscow, 117198, Russia

Location

Novartis Investigative Site

Moscow, 119992, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197022, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197341, Russia

Location

Novartis Investigative Site

Yaroslavl, 150047, Russia

Location

Novartis Investigative Site

Bucheon-si, Gyeonggi-do, 424-717, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 110 744, South Korea

Location

Novartis Investigative Site

Seville, Andalusia, 41071, Spain

Location

Novartis Investigative Site

Jerez de la Frontera, Cadiz, 11407, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08025, Spain

Location

Novartis Investigative Site

Centelles, Catalonia, 08540, Spain

Location

Novartis Investigative Site

Terrassa, Catalonia, 08221, Spain

Location

Novartis Investigative Site

A Coruña, Galicia, 15706, Spain

Location

Novartis Investigative Site

Madrid, Madrid, 28034, Spain

Location

Novartis Investigative Site

Madrid, Madrid, 28041, Spain

Location

Novartis Investigative Site

Port de Sagunt, Valencia, 46520, Spain

Location

Novartis Investigative Site

Taichung, Taiwan, 40447, Taiwan

Location

Novartis Investigative Site

Taipei, Taiwan, 114, Taiwan

Location

Novartis Investigative Site

Taipei, Taiwan, ROC, 112, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 24496699 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

sacubitril and valsartan sodium hydrate drug combination; olmesartan; Amlodipine; Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Study Directors
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2012
• First Posted: September 25, 2012
• Study Start: December 1, 2012
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: May 4, 2016
• Results First Posted: May 4, 2016

Record last verified: 2016-03

Locations

RU (6); ES (10); TW (3); AR (3); US (11); GR (3); CO (2); JP (1); IT (3); KR (2); FR (1); DE (2)