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

NCT01870739 | Completed Phase 2 Results

• 2 other identifiers: CLCZ696A22242012-005720-15
• Study Type: interventional
• Target: 115
• Locations: 3 countries
• Sites: 4

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.

Conditions

Hypertension

Keywords

LCZ696,; Hypertension,; Aortic stiffness,; Central blood pressure,; Cardiovascular MRI

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (7)

• Change From Baseline in Local Aortic Strain at 52 Weeks

  Baseline, 52 weeks

• Change From Baseline in Regional Aortic Pulse Wave Velocity at 52 Weeks

  Baseline, 52 weeks

• Change From Baseline in Central Blood Pressure at 52 Weeks

  Baseline, 52 weeks

• Change From Baseline in Augmentation Pressure at 52 Weeks

  Baseline, 52 weeks

• Change From Baseline in Augmentation Index at 52 Weeks

  Baseline, 52 weeks

Study Arms (2)

sacubitril/valsartan (LCZ696)

EXPERIMENTAL

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.

Drug: sacubitril/valsartan (LCZ696); Other: placebo to olmesartan; Drug: Amlodipine (Optional)

olmesartan

ACTIVE COMPARATOR

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.

Drug: olmesartan; Other: placebo to sacubitril/valsartan (LCZ696); Drug: Amlodipine (Optional)

Interventions

sacubitril/valsartan (LCZ696) DRUG

200 mg tablets

sacubitril/valsartan (LCZ696)

olmesartan DRUG

olmesartan

placebo to sacubitril/valsartan (LCZ696) OTHER

placebo

olmesartan

placebo to olmesartan OTHER

placebo

sacubitril/valsartan (LCZ696)

Amlodipine (Optional) DRUG

If required, open label amlodipine (2.5 mg, 5 mg, or 10 mg qd) was added to treatment regimen

olmesartan; sacubitril/valsartan (LCZ696)

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (4)

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Erlangen, 91054, Germany

Location

Novartis Investigative Site

Basel, 4031, Switzerland

Location

Novartis Investigative Site

Glasgow, Scotland, G12 8TA, United Kingdom

Location

Related Publications (2)

• Hrabak-Paar M, Kircher A, Al Sayari S, Kopp S, Santini F, Schmieder RE, Kachenoura N, Yates D, Langenickel T, Bremerich J, Heye T. Variability of MRI Aortic Stiffness Measurements in a Multicenter Clinical Trial Setting: Intraobserver, Interobserver, and Intracenter Variability of Pulse Wave Velocity and Aortic Strain Measurement. Radiol Cardiothorac Imaging. 2020 Apr 30;2(2):e190090. doi: 10.1148/ryct.2020190090. eCollection 2020 Apr.

  PMID: 33778551 DERIVED

• Santini F, Pansini M, Hrabak-Paar M, Yates D, Langenickel TH, Bremerich J, Bieri O, Schubert T. On the optimal temporal resolution for phase contrast cardiovascular magnetic resonance imaging: establishment of baseline values. J Cardiovasc Magn Reson. 2020 Oct 5;22(1):72. doi: 10.1186/s12968-020-00669-1.

  PMID: 33012283 DERIVED

Related Links

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

MeSH Terms

Conditions

Hypertension

Interventions

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

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Dihydropyridines; Pyridines

Results Point of Contact

• Title: Study Director
• 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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2013
• First Posted: June 6, 2013
• Study Start: October 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: January 5, 2021
• Results First Posted: September 1, 2016

Record last verified: 2019-03

Locations

GB (1); CH (1); DE (2)