Heart Failure With Preserved Ejection FractionPhase 4NCT06536309
Neprilysin Inhibition to Reduce Myocardial Fibrosis in Heart Failure With Preserved Ejection Fraction
A Phase 4 study testing Sacubitril-valsartan and Valsartan in people with Heart Failure With Preserved Ejection Fraction and Myocardial Fibrosis, run by Brigham and Women's Hospital.
Trial summary
Cardiac magnetic resonance imaging (MRI) measures of myocardial interstitial fibrosis (MIF) are elevated in heart failure with preserved ejection fraction (HFpEF) patients and associated with poor prognosis. Extracellular volume (ECV) is the most reproducible and best validated cardiac MRI measure of MIF. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction, Myocardial Fibrosis
- What is being tested?
- Sacubitril-valsartan and Valsartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 27 Aug 2026to 27 Aug 2026
- 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 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults aged 50 years or older
- Able to provide informed consent, as assessed by a physician investigator, and willing to comply with the study
- Clinically confirmed diagnosis of heart failure
- Left ventricular ejection fraction greater than or equal to 45% within 1 year by echocardiogram, cardiac MRI, or nuclear scan
Who cannot join
- Contraindication to MRI (metal prosthesis, implantable cardiac device, or severe claustrophobia)
- Systolic blood pressure < 100mm Hg, or <110 mm Hg for patients not taking an ACE inhibitor or angiotensin receptor blocker
- symptomatic hypotension
- eGFR < 30 mL/min/1.73m2 within 60 days of enrollment
- Serum potassium >5.2mmol/L within 60 days of enrollment, or >5.0 mmol/L for patients not taking an ACE inhibitor or angiotensin receptor blocker
- Myocardial infarction within 6 months of enrollment
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- Infiltrative or hypertrophic cardiomyopathy
- History of cirrhosis, biliary cirrhosis, or cholestasis
- History of angioedema
- Pregnancy, planning pregnancy, or breastfeeding
- Active treatment with lithium or a direct renin inhibitor
About this study
Cardiac magnetic resonance imaging (MRI) measures of myocardial interstitial fibrosis (MIF) are elevated in heart failure with preserved ejection fraction (HFpEF) patients and associated with poor prognosis. Extracellular volume (ECV) is the most reproducible and best validated cardiac MRI measure of MIF. Sacubitril/valsartan reduces histological MIF in mice and levels of some extracellular matrix regulatory proteins in humans with HFpEF. However, the effect of sacubitril/valsartan on robust measures of MIF in humans is unknown. Demonstrating reductions in ECV with sacubitril/valsartan would clarify the mechanism of this approved medication. Given the borderline reduction in heart failure hospitalizations with sacubitril/valsartan and the heterogeneity of HFpEF pathophysiology, this result would suggest that neprilysin inhibition may particularly benefit HFpEF patients with greater MIF. The investigators propose a proof-of-concept clinical trial to evaluate the effect of neprilysin inhibition (sacubitril/valsartan vs valsartan alone) on cardiac MRI measures of fibrosis (principally ECV) and circulating protein levels.
- Being tested
- Sacubitril-valsartan, Valsartan
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacubitril-valsartanDrug
Also called Entresto
Sacubitril-valsartan titrated to maximally targeted dose
ValsartanDrug
Also called Diovan
Valsartan titrated to maximally targeted dose
| Study group | Role | What they receive |
|---|---|---|
| Sacubitril/valsartan | Experimental | Patient randomized to the interventional arm will be treated with sacubitril/valsartan Receives: Drug: Sacubitril-valsartan |
| Valsartan | Active comparator | Patient randomized to the active comparator arm will be treated with valsartan Receives: Drug: Valsartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in extracellular volume by cardiac MRI
The primary outcome is to evaluate the change in extracellular volume (ECV), measured by cardiac MRI, from baseline to one year, in the sacubitril/valsartan arm compared to the valsartan arm
Measured: 1 year
Secondary outcomes (1)
Change in left ventricular native T1 time
Measured by cardiac MRI
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2024
- Study start27 Aug 2026
- Primary completion27 Aug 2026
- Study completion27 Aug 2026
Why it stopped: Due to changes in HFpEF treatment landscape, no recruitment activities were initiated and no participants were enrolled.
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 Preserved Ejection FractionStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jonathan Cunningham MD MPH, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06536309
- Sponsor's protocol ID
- 2024P001894
- Other IDs
- 1K23HL168163-01A1
- Status last verified
- Aug 2026
- First submitted
- 26 Jul 2024
- Last updated
- 31 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Deidentified participant data will be made available according to NHLBI and institutional regulations
Publications
Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, van Veldhuisen DJ, Zannad F, Zile MR, Desai AS, Claggett B, Jhund PS, Boytsov SA, Comin-Colet J, Cleland J, Dungen HD, Goncalvesova E, Katova T, Kerr Saraiva JF, Lelonek M, Merkely B, Senni M, Shah SJ, Zhou J, Rizkala AR, Gong J, Shi VC, Lefkowitz MP; PARAGON-HF Investigators and Committees. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2019 Oct 24;381(17):1609-1620. doi: 10.1056/NEJMoa1908655. Epub 2019 Sep 1.
PubMed 31475794
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neprilysin Inhibition to Reduce Myocardial Fibrosis in Heart Failure With Preserved Ejection Fraction
- ClinicalTrials.gov ID
- NCT06536309
- Acronym / sponsor ID
- 2024P001894
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Due to changes in HFpEF treatment landscape, no recruitment activities were initiated and no participants were enrolled.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 27 Aug 2026 (actual)
- Primary completion
- 27 Aug 2026 (actual)
- Study completion
- 27 Aug 2026 (actual)
- First posted
- 2 Aug 2024 (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.
Cardiac magnetic resonance imaging (MRI) measures of myocardial interstitial fibrosis (MIF) are elevated in heart failure with preserved ejection fraction (HFpEF) patients and associated with poor prognosis. Extracellular volume (ECV) is the most reproducible and best validated cardiac MRI measure of MIF. Sacubitril/valsartan reduces histological MIF in mice and levels of some extracellular matrix regulatory proteins in humans with HFpEF. However, the effect of sacubitril/valsartan on robust measures of MIF in humans is unknown. Demonstrating reductions in ECV with sacubitril/valsartan would clarify the mechanism of this approved medication. Given the borderline reduction in heart failure hospitalizations with sacubitril/valsartan and the heterogeneity of HFpEF pathophysiology, this result would suggest that neprilysin inhibition may particularly benefit HFpEF patients with greater MIF. The investigators propose a proof-of-concept clinical trial to evaluate the effect of neprilysin inhibition (sacubitril/valsartan vs valsartan alone) on cardiac MRI measures of fibrosis (principally ECV) and circulating protein levels.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sacubitril/valsartan | Experimental | Drug: Sacubitril-valsartanPatient randomized to the interventional arm will be treated with sacubitril/valsartan |
| Valsartan | Active comparator | Drug: ValsartanPatient randomized to the active comparator arm will be treated with valsartan |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adults aged 50 years or older
- Able to provide informed consent, as assessed by a physician investigator, and willing to comply with the study
- Clinically confirmed diagnosis of heart failure
- Left ventricular ejection fraction greater than or equal to 45% within 1 year by echocardiogram, cardiac MRI, or nuclear scan
Key exclusion criteria (11 listed)
- Contraindication to MRI (metal prosthesis, implantable cardiac device, or severe claustrophobia)
- Systolic blood pressure < 100mm Hg, or <110 mm Hg for patients not taking an ACE inhibitor or angiotensin receptor blocker
- symptomatic hypotension
- eGFR < 30 mL/min/1.73m2 within 60 days of enrollment
- Serum potassium >5.2mmol/L within 60 days of enrollment, or >5.0 mmol/L for patients not taking an ACE inhibitor or angiotensin receptor blocker
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 |
|---|---|---|
| Sacubitril-valsartanAlso: EntrestoSacubitril-valsartan titrated to maximally targeted dose | Drug | Sacubitril/valsartan |
| ValsartanAlso: DiovanValsartan titrated to maximally targeted dose | Drug | Valsartan |
Primary outcome
Change in extracellular volume by cardiac MRI
Time frame: 1 year
The primary outcome is to evaluate the change in extracellular volume (ECV), measured by cardiac MRI, from baseline to one year, in the sacubitril/valsartan arm compared to the valsartan arm
1 secondary outcome
Change in left ventricular native T1 time
Time frame: 1 year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
- Background: PubMed 31475794Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, van Veldhuisen DJ, Zannad F, Zile MR, Desai AS, Claggett B, Jhund PS, Boytsov SA, Comin-Colet J, Cleland J, Dungen HD, Goncalvesova E, Katova T, Kerr Saraiva JF, Lelonek M, Merkely B, Senni M, Shah SJ, Zhou J, Rizkala AR, Gong J, Shi VC, Lefkowitz MP; PARAGON-HF Investigators and Committees. Angiotensin-Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction. N Engl J Med. 2019 Oct 24;381(17):1609-1620. doi: 10.1056/NEJMoa1908655. Epub 2019 Sep 1.
- Individual participant dataSharing planned: No. Deidentified participant data will be made available according to NHLBI and institutional regulations
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sacubitril-valsartan and Valsartan in people with Heart Failure With Preserved Ejection Fraction and Myocardial Fibrosis, run by Brigham and Women's Hospital.
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 4 inclusion and 11 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: withdrawn, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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?
Change in extracellular volume by cardiac MRI (time frame: 1 year). 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 NCT06536309, 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 31 Aug 2026.