The ENVI Study: Effect of Entresto on Left Ventricular Remodelling on Cardiac MRI (ENVI)

April 20, 2023 updated by: University Hospital Southampton NHS Foundation Trust

Effect of Sacubitril/Valsartan (ENtresto) on Left Ventricular Reverse Remodelling as Demonstrated by Cardiac Magnetic Resonance (CMR) Imaging

A prospective, single centre, observational cohort study at University Hospital Southampton NHS Foundation Trust of 50 consecutive patients with Heart Failure with reduced Ejection Fraction and Ejection Fraction ≤35% who are eligible for sacubitril/valsartan (Entresto) initiation as per European Society of Cardiology guidelines.

Participants will have baseline and repeat cardiac magnetic resonance imaging (CMR) scans after 4-6 months of Entresto therapy. The CMR scans will be compared.

Clinical outcomes at 6 months including combined outcome of death and/or heart failure hospitalisation, KCCQ-12 questionnaire, 6-minute walk test, routine blood tests and NTproBNP will also be described.

This study will be the first to examine the effects of sacubitril/valsartan (Entresto) therapy on left ventricular reverse remodelling in patients with symptomatic HFrEF as demonstrated by Cardiac Magnetic Resonance Imaging.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The landmark trial PARADIGM-HF (2014) showed that a new drug sacubitril/valsartan (Entresto) was superior to a well-established drug (ACE-Inhibitors) for patients with severe heart failure. Entresto resulted in a 20% reduction in risk of death and hospitalisations, as well as improving quality of life and symptoms. This represented a major breakthrough in heart failure treatment and guidelines changed to recommend Entresto for patients in whom heart function had not improved on conventional heart failure drug treatments.

At the same point as recommending Entresto, international heart failure guidelines also recommend an Implantable Cardioverter-Defibrillator (ICD). An ICD is a device which can detect and treat potentially life-threatening heart rhythm abnormalities, which may occur in patients with persistently severe heart failure. The risk of complications associated with ICD implantation is not insignificant, up to 15%. Currently, there is a lack of consensus between clinicians regarding when best to offer ICD implantation in relation to Entresto treatment.

The exact mechanism of how Entresto achieves its beneficial effect is not fully understood. There are studies describing an improvement in heart function on Echocardiography (ultrasound). Some studies suggest a reduction in abnormal heart rhythms. There are however, no studies describing the effects of Entresto on heart tissue or function described on Cardiac Magnetic Resonance (CMR) Imaging. CMR is a specialised non-invasive scan which is excellent at looking at characteristics of heart tissue and is the gold standard for calculating heart function.

The study will enrol 50 patients who have been referred for Entresto treatment. Participants will undergo a baseline CMR to evaluate heart characteristics and function before being started on Entresto. After 6 months, participants will receive another CMR and the two scans will be compared for differences in heart size, function and tissue characteristics.

The Investigators hypothesize that there will be an improvement in a variety of CMR parameters and the findings will help better understand the mechanisms by which this is achieved e.g. reduction in fibrosis (subtle scarring) of heart tissue. The Investigators also believe a proportion of patients will avoid the need for an ICD, due to improvement in heart function.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United Kingdom
    • Hampshire
      • Southampton, Hampshire, United Kingdom, SO16 6YD
        • University Hospital Southampton NHS Foundation Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with symptomatic severe Heart Failure with reduced Ejection Fraction.

Description

Inclusion Criteria:

  • ≥18 years
  • HFrEF EF ≤35% despite optimisation of ACE-Inhibitor, Beta Blocker & Mineralocorticoid Receptor Antagonist and referred for Entresto initiation
  • Symptomatic NYHA II-III
  • Able and willing to provide informed consent
  • Able to undergo Cardiac Magnetic Resonance Imaging (CMR) scan

Exclusion Criteria:

  • Pre-existing cardiac device (i.e. pacemaker/defibrillator)
  • Symptomatic hypotension (BP <95mmHg) - [PARADIGM exclusion]
  • Severe renal failure (GFR <30)
  • Hyperkalaemia (K >5.4mmol/L)
  • History of angioedema
  • Diagnosis of amyloidosis, sarcoidosis or HCM
  • Myocardial infarction or revascularisation within the last 40 days
  • Valve disease expected to require surgery
  • Life expectancy <2 years secondary to any other cause (i.e. malignancy)
  • Pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Left Ventricular Volume quantified on Cardiac Magnetic Resonance Imaging
Time Frame: 6 months
Left ventricular Volume quantified in (ml)
6 months
Indexed Left Ventricular Volume quantified on Cardiac Magnetic Resonance Imaging
Time Frame: 6 months
Weight and Height will be combined to calculate Body Surface Area (m2). Left Ventricular Volume in (ml) will be divided by Body Surface Area to give indexed value (ml/m2)
6 months
Ejection Fraction quantified on Cardiac Magnetic Resonance Imaging
Time Frame: 6 months
Ejection Fraction quoted in (%)
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Cardiac Fibrosis quantification as measured by T1 mapping on Cardiac Magnetic Resonance Imaging
Time Frame: 6 months
6 months
Strain Analysis as measured by feature tracking on Cardiac Magnetic Resonance Imaging
Time Frame: 6 months
6 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Combined outcome of death and/or heart failure hospitalisation
Time Frame: 6 months
6 months
Quality of Life assessment: KCCQ-12 questionnaire
Time Frame: 6 months
Kansas City Cardiomyopathy Questionnaire.
6 months
Quality of Life assessment: 6 Minute Walk Test
Time Frame: 6 months
Distance walked (m) in 6 minutes
6 months
N-terminal pro B type natriuretic peptide (NTproBNP)
Time Frame: 6 months
Blood Test
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital Southampton NHS Foundation Trust

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Andrew S Flett, MBBS BSc MD, University Hospital Southampton NHS Foundation Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 9, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 23, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 23, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 5, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 26, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 27, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 21, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 20, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CAR0589

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

TBC

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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