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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01692301
First received: September 20, 2012
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

To examine 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).


Condition Intervention Phase
Hypertension
Drug: LCZ696
Drug: Olmesartan
Drug: LCZ696 matching placebo
Drug: Olmesartan matching placebo
Drug: amlodipine
Drug: hydrochlorothiazide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change from baseline in mean central aortic systolic blood pressure at 12 weeks [ Time Frame: baseline, 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in mean central pulse pressure [ Time Frame: baseline, 12 weeks, and 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean aortic pulse wave velocity [ Time Frame: baseline, 12 weeks, and 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean central aortic systolic blood pressure at 52 weeks [ Time Frame: baseline, 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean sitting systolic blood pressure [ Time Frame: baseline, 12 weeks, and 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean sitting diastolic blood pressure [ Time Frame: baseline, 12 weeks, and 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean sitting pulse pressure [ Time Frame: baseline, 12 weeks, and 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean arterial pressure [ Time Frame: baseline, 12 weeks, and 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean 24-hour systolic blood pressure [ Time Frame: baseline, 12 weeks, and 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean 24-hour diastolic blood pressure [ Time Frame: baseline, 12 weeks, and 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in mean 24-hour ambulatory pulse pressure [ Time Frame: baseline, 12 weeks, and 52 weeks ] [ Designated as safety issue: No ]

Enrollment: 439
Study Start Date: December 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LCZ696 Regimen
Randomized patients will receive LCZ696 once daily for four weeks, then will be force-titrated to a higher dose at Week 4 and will stay on this dose of LCZ696 once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP will be 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) will be given during the entire study.
Drug: LCZ696
Investigational drug
Drug: LCZ696 matching placebo
LCZ696 Matching Placebo tablet
Drug: Olmesartan matching placebo
Olmesartan matching placebo capsule
Drug: amlodipine
amlodipine 2.5 mg or 5 mg tablets
Drug: hydrochlorothiazide
hydrochlorothiazide 6.25mg, 12.5mg, or 25 mg tablets
Active Comparator: Olmesartan Regimen
Randomized patients will receive olmesartan once daily for four weeks, then will be force-titrated to a higher dose at Week 4 and will stay on this dose of olmesartan once daily for the remainder of the treatment period. At week 12, patients with uncontrolled BP will be 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) will be given during the entire study.
Drug: Olmesartan
Comparator Drug
Drug: LCZ696 matching placebo
LCZ696 Matching Placebo tablet
Drug: amlodipine
amlodipine 2.5 mg or 5 mg tablets
Drug: hydrochlorothiazide
hydrochlorothiazide 6.25mg, 12.5mg, or 25 mg tablets

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01692301

  Show 47 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01692301     History of Changes
Other Study ID Numbers: CLCZ696A2216, 2012-002899-14
Study First Received: September 20, 2012
Last Updated: August 4, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health
Brazil: Ministry of Health
Colombia: National Institutes of Health
France: Ministry of Health
Germany: Ministry of Health
Greece: Ministry of Health and Welfare
Italy: Ministry of Health
Japan: Ministry of Health, Labor and Welfare
Korea: Food and Drug Administration
Russia: Pharmacological Committee, Ministry of Health
Spain: Ministry of Health
Taiwan: Department of Health

Keywords provided by Novartis:
hypertension, elderly, central aortic pulse pressure, central pulse pressure, pulse wave velocity

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Olmesartan
Olmesartan medoxomil
Amlodipine
Hydrochlorothiazide
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on September 18, 2014