Heart FailurePhase 4VASCENDNCT03168568
Differential Vascular and Endocrine Effects of Valsartan/Sacubitril in Heart Failure With Reduced Ejection Fraction
A Phase 4 study of Heart Failure, run by University of Zurich at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 79 participants
- Where
- 1 siteSwitzerland
- Study dates
- 4 May 2017to 5 Sep 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the 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.
- Conditions
- Heart Failure
- Being tested
- Valsartan/Sacubitril or placebo, Valsartan or placebo
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Valsartan/Sacubitril or placeboDrug
Also called Entresto®; LCZ696
tablet (double dummy)
Valsartan or placeboDrug
Also called Diovan®
tablet (double dummy)
| Study group | Role | What they receive |
|---|---|---|
| Valsartan/Sacubitril | Experimental | Valsartan-Sacubitril 50mg/100mg twice daily, titrated to 200mg twice daily p.o. Duration of product administration: 3 months Receives: Drug: Valsartan/Sacubitril or placebo |
| Valsartan | Active comparator | Valsartan 40mg/80mg twice daily, titrated to 160mg twice daily p.o Duration of product administration: 3 months Receives: Drug: Valsartan or placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline, 3 months
Secondary outcomes (1)
Difference in flicker-induced vasodilatation of retinal arterioles and venules
Measured: Baseline, 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2017
- Study start4 May 2017
- Primary completion5 Sep 2020
- Study completion5 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03168568
- Sponsor's protocol ID
- VASCEND
- Acronym
- VASCEND
- Status last verified
- Nov 2020
- First submitted
- 22 May 2017
- Last updated
- 4 Nov 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Nagele MP, Haider T, Kreysing L, Barthelmes J, Nebunu D, Rossi VA, Hebeisen M, Sudano I, Ruschitzka F, Flammer AJ. Vascular Endothelial Effects of Sacubitril/Valsartan in Heart Failure With Reduced Ejection Fraction: Randomized Controlled Trial. JACC Adv. 2024 Nov 13;3(12):101392. doi: 10.1016/j.jacadv.2024.101392. eCollection 2024 Dec.
PubMed 39606217
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03168568
- Acronym / sponsor ID
- VASCEND / VASCEND
- Conditions
- Heart Failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 4 May 2017 (actual)
- Primary completion
- 5 Sep 2020 (actual)
- Study completion
- 5 Sep 2020 (actual)
- First posted
- 30 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Valsartan/Sacubitril | Experimental | Drug: Valsartan/Sacubitril or placeboValsartan-Sacubitril 50mg/100mg twice daily, titrated to 200mg twice daily p.o. Duration of product administration: 3 months |
| Valsartan | Active comparator | Drug: Valsartan or placeboValsartan 40mg/80mg twice daily, titrated to 160mg twice daily p.o Duration of product administration: 3 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Valsartan/Sacubitril or placeboAlso: Entresto®; LCZ696tablet (double dummy) | Drug | Valsartan/Sacubitril |
| Valsartan or placeboAlso: Diovan®tablet (double dummy) | Drug | Valsartan |
Primary outcome
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
1 secondary outcome
Difference in flicker-induced vasodilatation of retinal arterioles and venules
Time frame: Baseline, 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2020.
- Derived from this study: PubMed 39606217Nagele MP, Haider T, Kreysing L, Barthelmes J, Nebunu D, Rossi VA, Hebeisen M, Sudano I, Ruschitzka F, Flammer AJ. Vascular Endothelial Effects of Sacubitril/Valsartan in Heart Failure With Reduced Ejection Fraction: Randomized Controlled Trial. JACC Adv. 2024 Nov 13;3(12):101392. doi: 10.1016/j.jacadv.2024.101392. eCollection 2024 Dec.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study of Heart Failure, run by University of Zurich at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in flow-mediated vasodilatation (FMD) (time frame: Baseline, 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03168568, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2020.