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Differential Vascular and Endocrine Effects of Valsartan/Sacubitril in Heart Failure With Reduced Ejection Fraction (VASCEND)

Primary Purpose

Heart Failure

Status

Completed

Phase

Phase 4

Locations

Switzerland

Study Type

Interventional

Intervention

Valsartan/Sacubitril or placebo

Valsartan or placebo

About this trial

This is an interventional treatment trial for Heart Failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients ≥ 18 years of age, male or female, with a diagnosis of symptomatic heart failure (NYHA class II-IV) per ESC heart failure guidelines
LVEF ≤ 40%
Established guideline-recommended therapy with an ACEI, ARB and a beta-blocker, as clinically indicated and tolerated, at stable doses for at least 3 weeks prior to inclusion.

Exclusion Criteria:

History of hypersensitivity or allergy to any of the study drugs
History of angioedema.
Sitting systolic blood pressure <90 mmHg at Visit 1 (screening) or Visit 2 (randomization)
Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy).
Estimated GFR < 20 mL/min/1.73m2
Serum potassium > 5.5 mmol/L at Visit 1 (screening) or Visit 2 (randomization).
Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major CV surgery, percutaneous coronary intervention (PCI) or carotid angioplasty within the 3 months prior to Visit 1.
Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 3 months after Visit 1.
Implantation of a cardiac resynchronization therapy device (CRTD) within 2 months prior Visit 1 or intent to implant a CRTD within next 3 months.
History of heart transplant, on a transplant list or with ventricular assistance device (VAD).
Presence of significant endocrine diseases.
Presence of active acute infectious diseases.
Known narrow-angle glaucoma
Known epilepsy
Cimino-shunt operation on both arms
Pregnancy, intention thereof during study; lack of sufficient contraception; breastfeeding

Sites / Locations

University Heart Center Zurich

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Valsartan/Sacubitril

Valsartan

Arm Description

Valsartan-Sacubitril 50mg/100mg twice daily, titrated to 200mg twice daily p.o. Duration of product administration: 3 months

Valsartan 40mg/80mg twice daily, titrated to 160mg twice daily p.o Duration of product administration: 3 months

Outcomes

Primary Outcome Measures

Difference in flow-mediated vasodilatation (FMD)

Difference in flow-mediated vasodilatation (FMD, percent dilatation of brachial artery after blood pressure cuff occlusion) between the valsartan/sacubitril and valsartan group as assessed at the final study visit

Secondary Outcome Measures

Difference in flicker-induced vasodilatation of retinal arterioles and venules

Full Information

NCT ID

NCT03168568

First Posted

May 22, 2017

Last Updated

November 3, 2020

Sponsor

University of Zurich

Collaborators

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03168568

Brief Title

Differential Vascular and Endocrine Effects of Valsartan/Sacubitril in Heart Failure With Reduced Ejection Fraction

Acronym

VASCEND

Official Title

Differential Vascular and Endocrine Effects of Valsartan/Sacubitril in Heart Failure With Reduced Ejection Fraction: A Double-blind Randomized Controlled Phase IV Trial (VASCEND)

Study Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Completed

Study Start Date

May 4, 2017 (Actual)

Primary Completion Date

September 5, 2020 (Actual)

Study Completion Date

September 5, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Zurich

Collaborators

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

The objective of this study is to evaluate whether valsartan/sacubitril leads to a superior improvement in endothelial function and endocrine status compared to valsartan alone.

Detailed Description

Valsartan/sacubitril (Entresto®; LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) that has recently been approved for the treatment of chronic heart failure with reduced ejection fraction (HFrEF). The drug consists of a 1:1 complex of the angiotensin receptor blocker (ARB) valsartan and the neprilysin inhibitor sacubitril. In a recent randomized controlled trial in patients with heart failure and reduced ejection fraction (PARADIGM-HF), valsartan/sacubitril significantly reduced all-cause and cardiovascular mortality as well as hospitalizations for heart failure compared to enalapril. The precise reason why combined angiotensin receptor and neprilysin blockade is superior to ACE blockade is still unclear and knowledge of the mechanisms involved would provide further insight which patients with symptomatic heart failure will particularly benefit from valsartan/sacubitril. On the one hand, many of the peptides affected by neprilysin blockade act on vascular endothelial cells. On the other, neprilysin inhibition may induce significant endocrine changes with a shift to more favorable hormonal profile in HFrEF patients. Detailed studies on the vascular and endocrine effects of valsartan/sacubitril in humans are lacking so far. The investigators hypothesize that valsartan/sacubitril results in an incremental improvement of endothelial dysfunction and endocrine imbalance over valsartan in patients with heart failure with reduced ejection fraction.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Heart Failure

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

79 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Valsartan/Sacubitril

Arm Type

Experimental

Arm Description

Valsartan-Sacubitril 50mg/100mg twice daily, titrated to 200mg twice daily p.o. Duration of product administration: 3 months

Arm Title

Valsartan

Arm Type

Active Comparator

Arm Description

Valsartan 40mg/80mg twice daily, titrated to 160mg twice daily p.o Duration of product administration: 3 months

Intervention Type

Drug

Intervention Name(s)

Valsartan/Sacubitril or placebo

Other Intervention Name(s)

Entresto®; LCZ696

Intervention Description

tablet (double dummy)

Intervention Type

Drug

Intervention Name(s)

Valsartan or placebo

Other Intervention Name(s)

Diovan®

Intervention Description

tablet (double dummy)

Primary Outcome Measure Information:

Title

Difference in flow-mediated vasodilatation (FMD)

Description

Time Frame

Baseline, 3 months

Secondary Outcome Measure Information:

Title

Difference in flicker-induced vasodilatation of retinal arterioles and venules

Time Frame

Baseline, 3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients ≥ 18 years of age, male or female, with a diagnosis of symptomatic heart failure (NYHA class II-IV) per ESC heart failure guidelines LVEF ≤ 40% Established guideline-recommended therapy with an ACEI, ARB and a beta-blocker, as clinically indicated and tolerated, at stable doses for at least 3 weeks prior to inclusion. Exclusion Criteria: History of hypersensitivity or allergy to any of the study drugs History of angioedema. Sitting systolic blood pressure <90 mmHg at Visit 1 (screening) or Visit 2 (randomization) Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy). Estimated GFR < 20 mL/min/1.73m2 Serum potassium > 5.5 mmol/L at Visit 1 (screening) or Visit 2 (randomization). Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major CV surgery, percutaneous coronary intervention (PCI) or carotid angioplasty within the 3 months prior to Visit 1. Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 3 months after Visit 1. Implantation of a cardiac resynchronization therapy device (CRTD) within 2 months prior Visit 1 or intent to implant a CRTD within next 3 months. History of heart transplant, on a transplant list or with ventricular assistance device (VAD). Presence of significant endocrine diseases. Presence of active acute infectious diseases. Known narrow-angle glaucoma Known epilepsy Cimino-shunt operation on both arms Pregnancy, intention thereof during study; lack of sufficient contraception; breastfeeding

Facility Information:

Facility Name

University Heart Center Zurich

City

Zurich

ZIP/Postal Code

8091

Country

Switzerland

12. IPD Sharing Statement

Learn more about this trial

Differential Vascular and Endocrine Effects of Valsartan/Sacubitril in Heart Failure With Reduced Ejection Fraction

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