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

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ClinicalTrials.gov Identifier: NCT03168568
Recruitment Status : Recruiting
First Posted : May 30, 2017
Last Update Posted : December 4, 2018
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
University of Zurich

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.

Condition or disease Intervention/treatment Phase
Heart Failure Drug: Valsartan/Sacubitril or placebo Drug: Valsartan or placebo Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : May 4, 2017
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : June 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure
Drug Information available for: Valsartan

Arm Intervention/treatment
Experimental: Valsartan/Sacubitril
Valsartan-Sacubitril 50mg/100mg twice daily, titrated to 200mg twice daily p.o. Duration of product administration: 3 months
Drug: Valsartan/Sacubitril or placebo
tablet (double dummy)
Other Name: Entresto®; LCZ696

Active Comparator: Valsartan
Valsartan 40mg/80mg twice daily, titrated to 160mg twice daily p.o Duration of product administration: 3 months
Drug: Valsartan or placebo
tablet (double dummy)
Other Name: Diovan®




Primary Outcome Measures :
  1. Difference in flow-mediated vasodilatation (FMD) [ Time Frame: Baseline, 3 months ]
    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 :
  1. Difference in flicker-induced vasodilatation of retinal arterioles and venules [ Time Frame: Baseline, 3 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients ≥ 18 years of age, male or female, with a diagnosis of symptomatic heart failure (NYHA class II-IV) per ESC heart failure guidelines
  2. LVEF ≤ 40%
  3. 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:

  1. History of hypersensitivity or allergy to any of the study drugs
  2. History of angioedema.
  3. Sitting systolic blood pressure <90 mmHg at Visit 1 (screening) or Visit 2 (randomization)
  4. Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy).
  5. Estimated GFR < 20 mL/min/1.73m2
  6. Serum potassium > 5.5 mmol/L at Visit 1 (screening) or Visit 2 (randomization).
  7. 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.
  8. Coronary or carotid artery disease likely to require surgical or percutaneous intervention within the 3 months after Visit 1.
  9. Implantation of a cardiac resynchronization therapy device (CRTD) within 2 months prior Visit 1 or intent to implant a CRTD within next 3 months.
  10. History of heart transplant, on a transplant list or with ventricular assistance device (VAD).
  11. Presence of significant endocrine diseases.
  12. Presence of active acute infectious diseases.
  13. Known narrow-angle glaucoma
  14. Known epilepsy
  15. Cimino-shunt operation on both arms
  16. Pregnancy, intention thereof during study; lack of sufficient contraception; breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03168568


Contacts
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Contact: Frank Ruschitzka, Prof,MD +41442553353 frank.ruschitzka@usz.ch
Contact: Silviya Cantatore, RN +41442552280 silviya.cantatore@usz.ch

Locations
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Switzerland
University Heart Center Zurich Recruiting
Zurich, Switzerland, 8091
Contact: Frank Ruschitzka, MD    +41442553353    frank.ruschitzka@usz.ch   
Sponsors and Collaborators
University of Zurich
Novartis Pharmaceuticals

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Responsible Party: University of Zurich
ClinicalTrials.gov Identifier: NCT03168568     History of Changes
Other Study ID Numbers: VASCEND
First Posted: May 30, 2017    Key Record Dates
Last Update Posted: December 4, 2018
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Valsartan
LCZ 696
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action