Heart Failure With Reduced Ejection FractionENVINCT05348226
The ENVI Study: Effect of Entresto on Left Ventricular Remodelling on Cardiac MRI
An observational study of Heart Failure With Reduced Ejection Fraction, run by University Hospital Southampton NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction
- What is being tested?
- Additional Cardiac Magnetic Resonance Scan
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 9 Jun 2021to 23 Mar 2023
- Phase
- Observational
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with symptomatic severe Heart Failure with reduced Ejection Fraction.
Who may be able to join
- ≥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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospital Southampton NHS Foundation Trust
Southampton, Hampshire, SO16 6YD
About this study
Official title: 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.
Read more
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.
Read the 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.
- Being tested
- Additional Cardiac Magnetic Resonance Scan
- Keywords
- Cardiac Magnetic Resonance Imaging
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Additional Cardiac Magnetic Resonance ScanDiagnostic test
Standard of care medical treatment with sacubitril/valsartan (Entresto). Additional Cardiac Magnetic Resonance Imaging (CMR) Scan after 4-6 months of treatment.
What is being measured
The primary outcome is the main question the study is designed to answer.
Left Ventricular Volume quantified on Cardiac Magnetic Resonance Imaging
Left ventricular Volume quantified in (ml)
Measured: 6 months
Indexed Left Ventricular Volume quantified on Cardiac Magnetic Resonance Imaging
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)
Measured: 6 months
Ejection Fraction quantified on Cardiac Magnetic Resonance Imaging
Ejection Fraction quoted in (%)
Measured: 6 months
Secondary outcomes (2)
Cardiac Fibrosis quantification as measured by T1 mapping on Cardiac Magnetic Resonance Imaging
Measured: 6 months
Strain Analysis as measured by feature tracking on Cardiac Magnetic Resonance Imaging
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2022
- Study start9 Jun 2021
- Primary completion23 Mar 2023
- Study completion23 Mar 2023
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 Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Southampton NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrew S Flett, MBBS BSc MD, Principal investigator, University Hospital Southampton NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05348226
- Sponsor's protocol ID
- CAR0589
- Acronym
- ENVI
- Status last verified
- Apr 2023
- First submitted
- 5 Apr 2022
- Last updated
- 21 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: TBC
Publications
Zheng A, Adam R, Peebles C, Harden S, Shambrook J, Abbas A, Vedwan K, Adam G, Haydock P, Cowburn P, Young C, Long J, Walkden M, Smith S, Greenwood E, Olden P, Flett A. Effect of optimisation to contemporary HFrEF medical therapy with sacubitril/valsartan (Entresto) and dapaglifloziN on left Ventricular reverse remodelling as demonstrated by cardiac magnetic resonance (CMR) Imaging: the ENVI study. Open Heart. 2024 Dec 2;11(2):e002933. doi: 10.1136/openhrt-2024-002933.
PubMed 39622578
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Sacubitril/Valsartan (ENtresto) on Left Ventricular Reverse Remodelling as Demonstrated by Cardiac Magnetic Resonance (CMR) Imaging
- ClinicalTrials.gov ID
- NCT05348226
- Acronym / sponsor ID
- ENVI / CAR0589
- Keywords
- Cardiac Magnetic Resonance Imaging
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University Hospital Southampton NHS Foundation TrustUniversity, hospital or other
- Study start
- 9 Jun 2021 (actual)
- Primary completion
- 23 Mar 2023 (actual)
- Study completion
- 23 Mar 2023 (actual)
- First posted
- 27 Apr 2022 (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.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with symptomatic severe Heart Failure with reduced Ejection Fraction.
Key inclusion criteria (5 listed)
- ≥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
Key exclusion criteria (10 listed)
- 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
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 |
|---|---|---|
| Additional Cardiac Magnetic Resonance ScanStandard of care medical treatment with sacubitril/valsartan (Entresto). Additional Cardiac Magnetic Resonance Imaging (CMR) Scan after 4-6 months of treatment. | Diagnostic test | – |
Primary outcome
Left Ventricular Volume quantified on Cardiac Magnetic Resonance Imaging
Time frame: 6 months
Left ventricular Volume quantified in (ml)
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)
Ejection Fraction quantified on Cardiac Magnetic Resonance Imaging
Time frame: 6 months
Ejection Fraction quoted in (%)
2 secondary outcomes
Cardiac Fibrosis quantification as measured by T1 mapping on Cardiac Magnetic Resonance Imaging
Time frame: 6 months
Strain Analysis as measured by feature tracking on Cardiac Magnetic Resonance Imaging
Time frame: 6 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 21 Apr 2023.
- Derived from this study: PubMed 39622578Zheng A, Adam R, Peebles C, Harden S, Shambrook J, Abbas A, Vedwan K, Adam G, Haydock P, Cowburn P, Young C, Long J, Walkden M, Smith S, Greenwood E, Olden P, Flett A. Effect of optimisation to contemporary HFrEF medical therapy with sacubitril/valsartan (Entresto) and dapaglifloziN on left Ventricular reverse remodelling as demonstrated by cardiac magnetic resonance (CMR) Imaging: the ENVI study. Open Heart. 2024 Dec 2;11(2):e002933. doi: 10.1136/openhrt-2024-002933.
- Individual participant dataSharing planned: Undecided. TBC
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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.
Andrew S Flett, MBBS BSc MD principal investigator
University Hospital Southampton NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Failure With Reduced Ejection Fraction, run by University Hospital Southampton NHS Foundation Trust at 1 site in United Kingdom.
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 5 inclusion and 10 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 21 Apr 2023. 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 United Kingdom. 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.
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?
Left Ventricular Volume quantified on Cardiac Magnetic Resonance Imaging (time frame: 6 months). The study lists 3 primary outcomes in all. 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 NCT05348226, 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 21 Apr 2023.