A Study to Evaluate the Effect of LCZ696 on Aortic Stiffness in Subjects With Hypertension

Hypertension Clinical Trial

Official title:

A Randomized, Double-blind, Active-controlled, Parallel Group, 52-week Study to Evaluate the Effect of LCZ696 Compared to Olmesartan on Regional Aortic Stiffness in Subjects With Essential Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01870739
• Other study ID #: CLCZ696A2224
• Secondary ID: 2012-005720-15
• Status: Completed
• Phase: Phase 2
• Start date: October 2013
• Est. completion date: June 2015

Study information

• Verified date: March 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This was the first evaluation of the effects of LCZ696 on local and regional measures of aortic stiffness in subjects with mild to moderate hypertension and widened pulse pressure. The results of this exploratory study will help to understand the mechanism of action of LCZ696 and used to inform the design of future clinical studies with LCZ696 in subjects with cardiovascular diseases.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 115
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Subjects with essential hypertension, untreated or currently taking antihypertensive therapy

Key exclusion Criteria:

• women of child bearing potential (WOCBP) if not on highly effective contraception

• Malignant or severe hypertension (grade 3 of WHO classification)

• History or evidence of a secondary form of hypertension

• Transient ischemic cerebral attack (TIA) during the 12 months prior to screening or any history of stroke.

• Previous or current diagnosis of heart failure (New York Heart Association Class II-IV).

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• sacubitril/valsartan (LCZ696)
200 mg tablets
• olmesartan

Other:
• placebo to sacubitril/valsartan (LCZ696)
placebo
• placebo to olmesartan
placebo

Drug:
• Amlodipine (Optional)
If required, open label amlodipine (2.5 mg, 5 mg, or 10 mg qd) was added to treatment regimen

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Erlangen
Switzerland	Novartis Investigative Site	Basel
United Kingdom	Novartis Investigative Site	Glasgow	Scotland

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Germany,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Ascending Aorta Distensibility at 52 Week	Cardiovascular magnetic resonance imaging (MRI) scans were obtained at baseline prior to randomization, at week 52 for the assessment of local aortic distensibility. Ascending aorta distensibility was one of the 3 components for measuring local arota distensibility.	Baseline, 52 weeks
Primary	Change From Baseline in Proximal Descending Aorta Distensibility at 52 Weeks	Cardiovascular magnetic resonance imaging (MRI) scans were obtained at baseline prior to randomization, at week 52 for the assessment of local aortic distensibility. Proximal descending aorta distensibility was one of the 3 components for measuring local arota distensibility.	Baseline, 52 weeks
Primary	Change From Baseline in Distal Descending Aorta Distensibility at 52 Weeks	Cardiovascular magnetic resonance imaging (MRI) scans were obtained at baseline prior to randomization, at week 52 for the assessment of local aortic distensibility. Distal descending aorta distensibility was one of the 3 components for measuring local arota distensibility.	Baseline, 52 weeks
Secondary	Change From Baseline in Local Aortic Strain at 52 Weeks	Cardiovascular magnetic resonance imaging (MRI) scans were obtained at baseline prior to randomization, at week 52 for the assessment of local aortic strain. Local aortic strain was measured by assessing ascending aorta strain, proximal descending aorta strain and distal descending aorta strain.	Baseline, 52 weeks
Secondary	Change From Baseline in Regional Aortic Pulse Wave Velocity at 52 Weeks	Cardiovascular magnetic resonance imaging (MRI) scans were obtained at baseline prior to randomization, at week 52 for the assessment of regional aortic pulse wave velocity.	Baseline, 52 weeks
Secondary	Change From Baseline in Central Blood Pressure at 52 Weeks	Central blood pressure was determined by measuring central systolic blood pressure , diastolic blood pressure and pulse pressure.	Baseline, 52 weeks
Secondary	Change From Baseline in Augmentation Pressure at 52 Weeks	Augmentation pressure is the added pressure during systole due to wave reflection.	Baseline, 52 weeks
Secondary	Change From Baseline in Augmentation Index at 52 Weeks	Augmentation index (Alx) is the percentage of the central pulse pressure due to wave reflection.	Baseline, 52 weeks
Secondary	Change From Baseline in Carotid-femoral Pulse Wave Velocity at 52 Weeks	For pulse wave velocity calculation, the pressure waveform at the femoral site (using a partially inflated custom blood pressure cuff) and the carotid site (using hand -held applanation tonometry) were measured simultaneously. Pulse wave analysis was performed on the central aortic pressure waveform as derived from the brachial pressure waveform recorded in a partially-inflated blood pressure cuff around the upper arm.	Baseline, 52 weeks
Secondary	Number of Patients With Reported Adverse Events, Serious Adverse Events and Death	This outcome measure summarizes patients with any adverse events, serious adverse events and death.	12 weeks

External Links

•   A Plain Language Trial Summary is available on novartisclinicaltrials.com