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

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ClinicalTrials.gov Identifier: NCT01870739
Recruitment Status : Completed
First Posted : June 6, 2013
Results First Posted : September 1, 2016
Last Update Posted : April 9, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE June 3, 2013
First Posted Date  ICMJE June 6, 2013
Results First Submitted Date  ICMJE May 31, 2016
Results First Posted Date  ICMJE September 1, 2016
Last Update Posted Date April 9, 2019
Study Start Date  ICMJE October 2013
Actual Primary Completion Date June 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 20, 2016)
  • Change From Baseline in Ascending Aorta Distensibility at 52 Week [ Time Frame: Baseline, 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. Ascending aorta distensibility was one of the 3 components for measuring local arota distensibility.
  • Change From Baseline in Proximal Descending Aorta Distensibility at 52 Weeks [ Time Frame: Baseline, 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.
  • Change From Baseline in Distal Descending Aorta Distensibility at 52 Weeks [ Time Frame: Baseline, 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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 3, 2013)
  • Change from baseline in ascending aorta distensibility at 12 weeks [ Time Frame: Baseline, 12 weeks ]
    Cardiovascular magnetic resonance imaging (MRI) scans will be obtained at baseline prior to randomization, at week 12 for the assessment of local aortic distensibility.
  • Change from baseline in proximal descending aorta distensibility at 12 weeks [ Time Frame: Baseline, 12 weeks ]
    Cardiovascular magnetic resonance imaging (MRI) scans will be obtained at baseline prior to randomization, at week 12 for the assessment of local aortic distensibility.
  • Change from baseline in distal descending aorta distensibility at 12 weeks [ Time Frame: Baseline, 12 weeks ]
    Cardiovascular magnetic resonance imaging (MRI) scans will be obtained at baseline prior to randomization, at week 12 for the assessment of local aortic distensibility.
Change History Complete list of historical versions of study NCT01870739 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2016)
  • Change From Baseline in Local Aortic Strain at 52 Weeks [ Time Frame: Baseline, 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.
  • Change From Baseline in Regional Aortic Pulse Wave Velocity at 52 Weeks [ Time Frame: Baseline, 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.
  • Change From Baseline in Central Blood Pressure at 52 Weeks [ Time Frame: Baseline, 52 weeks ]
    Central blood pressure was determined by measuring central systolic blood pressure , diastolic blood pressure and pulse pressure.
  • Change From Baseline in Augmentation Pressure at 52 Weeks [ Time Frame: Baseline, 52 weeks ]
    Augmentation pressure is the added pressure during systole due to wave reflection.
  • Change From Baseline in Augmentation Index at 52 Weeks [ Time Frame: Baseline, 52 weeks ]
    Augmentation index (Alx) is the percentage of the central pulse pressure due to wave reflection.
  • Change From Baseline in Carotid-femoral Pulse Wave Velocity at 52 Weeks [ Time Frame: Baseline, 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.
  • Number of Patients With Reported Adverse Events, Serious Adverse Events and Death [ Time Frame: 12 weeks ]
    This outcome measure summarizes patients with any adverse events, serious adverse events and death.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 3, 2013)
  • Change from baseline in local aortic strain at 12 weeks [ Time Frame: Baseline, 12 weeks ]
    Cardiovascular magnetic resonance imaging (MRI) scans will be obtained at baseline prior to randomization, at week 12 for the assessment of local aortic strain.
  • Change from baseline in regional aortic pulse wave velocity at 12 weeks [ Time Frame: Baseline, 12 weeks ]
    Cardiovascular magnetic resonance imaging (MRI) scans will be obtained at baseline prior to randomization, at week 12 for the assessment of regional aortic pulse wave velocity.
  • Change from baseline in Central blood pressure at 12 weeks [ Time Frame: Baseline, 12 weeks ]
  • Change from baseline in augmentation pressure at 12 weeks [ Time Frame: Baseline, 12 weeks ]
    Augmentation pressure is the added pressure during systole due to wave reflection.
  • Change from baseline in augmentation index at 12 weeks [ Time Frame: Baseline, 12 weeks ]
    Augmentation index is the percentage of the central pulse pressure due to wave reflection.
  • Change from baseline in pulse wave velocity at 12 weeks [ Time Frame: Baseline, 12 weeks ]
  • Number of Patients With Reported Adverse Events, Serious Adverse Events and Death [ Time Frame: 12 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Effect of LCZ696 on Aortic Stiffness in Subjects With Hypertension
Official Title  ICMJE 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
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Hypertension
Intervention  ICMJE
  • Drug: sacubitril/valsartan (LCZ696)
    200 mg tablets
  • Drug: olmesartan
  • Other: placebo to sacubitril/valsartan (LCZ696)
    placebo
  • Other: 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
Study Arms  ICMJE
  • Experimental: sacubitril/valsartan (LCZ696)

    Single drug treatment period: Patients received LCZ696 200mg once daily (q.d.) + placebo to 20 mg olmesartan q.d for 2 weeks. After 2 weeks, patients were dosed at the maintenance dose level (400 mg qd LCZ696 + placebo to 40 mg qd olmesartan) for 10 weeks.

    Add-on Period: After 12 weeks on single-drug treatment, patients continued in the study on the blinded maintenance dose and if required, open label amlodipine (2.5 mg, 5 mg, or 10 mg qd) was added to the treatment regimen and titrated according to the investigator's discretion to achieve target blood pressure.

    Interventions:
    • Drug: sacubitril/valsartan (LCZ696)
    • Other: placebo to olmesartan
    • Drug: Amlodipine (Optional)
  • Active Comparator: olmesartan

    Single drug treatment period: Patients received 20 mg olmesartan q.d + placebo to LCZ696 200mg once daily (q.d.) for 2 weeks. After 2 weeks, patients were dosed at the maintenance dose level (40 mg olmesartan q.d + placebo to 400 mg qd LCZ696) for 10 weeks.

    Add-on Period: After 12 weeks on single-drug treatment, patients continued in the study on the blinded maintenance dose and if required, open label amlodipine (2.5 mg, 5 mg, or 10 mg qd) was added to the treatment regimen and titrated according to the investigator's discretion to achieve target blood pressure.

    Interventions:
    • Drug: olmesartan
    • Other: placebo to sacubitril/valsartan (LCZ696)
    • Drug: Amlodipine (Optional)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 20, 2016)
115
Original Estimated Enrollment  ICMJE
 (submitted: June 3, 2013)
140
Actual Study Completion Date  ICMJE June 2015
Actual Primary Completion Date June 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Switzerland,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01870739
Other Study ID Numbers  ICMJE CLCZ696A2224
2012-005720-15 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP