Hypertensive Heart DiseasePhase 2REVERSE-LVHNCT03553810
Role of ARNi in Ventricular Remodeling in Hypertensive LVH
A Phase 2 study testing Entresto and Valsartan in people with Hypertensive Heart Disease, run by National Heart Centre Singapore at 1 site in Singapore.
Trial summary
In Singapore, hypertension is very common in the adult population. Hypertensive heart disease is a leading cause of heart failure and cardiovascular death. Current management relies primarily on achieving blood pressure targets. Read more about this study
- Who is it for?
- Ages 21 to 99 years
- Conditions the study is for
- Hypertensive Heart Disease
- What is being tested?
- Entresto and Valsartan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteSingapore
- Study dates
- 12 Apr 2019to 28 Jun 2024
- Phase
- Phase 2
- 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 21 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Increased left ventricular mass on cardiovascular magnetic resonance (based on established local age- and sex-specific CMR ranges)
- Essential hypertension
Who cannot join
- Known secondary causes of hypertension
- Previous intolerance to angiotensin receptor blockers
- History of heart failure
- Stage IV/V chronic renal disease (eGFR < 30ml/min/1.73m2)
- Patients with serum potassium > 5.2 mmol/L (mEg/L) at Visit 1
- History of cardiovascular events (myocardial infarction, strokes and transient ischemic attacks)
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- Known atrial fibrillation
- Being unable to understand or comply with study procedures (including CMR)
- History or presence of any other disease with a life expectancy of < 3 years
- Pregnant or nursing (lactating) women
Trial locations and contacts
1 site in 1 country.
About this study
In Singapore, hypertension is very common in the adult population. Hypertensive heart disease is a leading cause of heart failure and cardiovascular death. Current management relies primarily on achieving blood pressure targets. However, the optimal blood pressure goals are controversial and there are inherent difficulties in measuring blood pressure using external devices applied to peripheral arteries. As a result of (usually longstanding) hypertension, the heart thickens (i.e. hypertrophies) to maintain function. Ultimately, HF may occur due to long standing energy deficits, muscle injury/death and diffuse interstitial fibrosis (heart muscle scarring). In an ongoing study (REMODEL, ClinicalTrial.gov Identifier NCT02670031), we have been able to undertake preliminary analyses with respect to factors associated with the development of fibrosis. In this randomize controlled trial, we will be examining a novel therapy that has the potential to induce regression cardiac hypertrophy and fibrosis.
- Conditions
- Hypertensive Heart Disease
- Being tested
- Entresto, Valsartan
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EntrestoDrug
Also called Valsartan/sacubitril
Entresto (Valsartan/sacubitril) 100mg once a day, up-titrating to 200mg or maximum 400mg to achieve target systolic blood pressure below 140 mmHg, over a duration of 52 weeks. If necessary, amlodipine and/or hydrochlorothiazide may be added to achieve target systolic blood pressure.
ValsartanDrug
Valsartan 40mg once a day, up-titrating to 80 or maximum 160 mg to achieve target systolic blood pressure below 140mmHg, over a duration of 52 weeks. If necessary, amlodipine and/or hydrochlorothiazide may be added to achieve target systolic blood pressure.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Entresto (valsartan/sacubitril) 100mg once a day Receives: Drug: Entresto |
| Controlled Arm | Active comparator | Valsartan 40mg once a day Receives: Drug: Valsartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fibrosis volume
A difference in terms of change in interstitial volume from baseline following 52 weeks of treatment. Extracellular volume fraction (ECV) will be quantified from native and post-contrast myocardial T1. Fibrosis volume is defined as ECV x myocardial volume and indexed to body surface area (ml/m2)
Measured: 52 weeks
Secondary outcomes (2)
Left ventricular mass measured on CMR
Changes from baseline in left ventricular mass, indexed to body surface area (g/m2).
Measured: 52 weeks
Biomarker/biochemistry
Identify potential markers as indicators of cardiac structural effects of ARNi and ARB
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2018
- Study start12 Apr 2019
- Primary completion28 Jun 2024
- Study completion28 Jun 2024
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 Hypertensive Heart DiseaseStudies 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Heart Centre Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- National Medical Research Council (NMRC), Singapore
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03553810
- Sponsor's protocol ID
- 2018/2182
- Acronym
- REVERSE-LVH
- Status last verified
- Jun 2025
- First submitted
- 4 Apr 2018
- Last updated
- 26 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lee V, Zheng Q, Toh DF, Pua CJ, Bryant JA, Lee CH, Cook SA, Butler J, Diez J, Richards AM, Le TT, Chin CWL. Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocol. Front Cardiovasc Med. 2023 Aug 22;10:1248468. doi: 10.3389/fcvm.2023.1248468. eCollection 2023.
PubMed 37674806
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of ARNi in Ventricular Remodeling in Hypertensive LVH
- ClinicalTrials.gov ID
- NCT03553810
- Acronym / sponsor ID
- REVERSE-LVH / 2018/2182
- Conditions
- Hypertensive Heart Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- National Heart Centre SingaporeUniversity, hospital or other
- Collaborators
- National Medical Research Council (NMRC), Singapore
- Study start
- 12 Apr 2019 (actual)
- Primary completion
- 28 Jun 2024 (actual)
- Study completion
- 28 Jun 2024 (actual)
- First posted
- 12 Jun 2018 (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.
In Singapore, hypertension is very common in the adult population. Hypertensive heart disease is a leading cause of heart failure and cardiovascular death. Current management relies primarily on achieving blood pressure targets. However, the optimal blood pressure goals are controversial and there are inherent difficulties in measuring blood pressure using external devices applied to peripheral arteries. As a result of (usually longstanding) hypertension, the heart thickens (i.e. hypertrophies) to maintain function. Ultimately, HF may occur due to long standing energy deficits, muscle injury/death and diffuse interstitial fibrosis (heart muscle scarring). In an ongoing study (REMODEL, ClinicalTrial.gov Identifier NCT02670031), we have been able to undertake preliminary analyses with respect to factors associated with the development of fibrosis. In this randomize controlled trial, we will be examining a novel therapy that has the potential to induce regression cardiac hypertrophy and fibrosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: EntrestoEntresto (valsartan/sacubitril) 100mg once a day |
| Controlled Arm | Active comparator | Drug: ValsartanValsartan 40mg once a day |
Who may qualify
- Ages
- 21 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Increased left ventricular mass on cardiovascular magnetic resonance (based on established local age- and sex-specific CMR ranges)
- Essential hypertension
Key exclusion criteria (10 listed)
- Known secondary causes of hypertension
- Previous intolerance to angiotensin receptor blockers
- History of heart failure
- Stage IV/V chronic renal disease (eGFR < 30ml/min/1.73m2)
- Patients with serum potassium > 5.2 mmol/L (mEg/L) at Visit 1
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 |
|---|---|---|
| EntrestoAlso: Valsartan/sacubitrilEntresto (Valsartan/sacubitril) 100mg once a day, up-titrating to 200mg or maximum 400mg to achieve target systolic blood pressure below 140 mmHg, over a duration of 52 weeks. If necessary, amlodipine and/or hydrochlorothiazide may be added to achieve target systolic blood pressure. | Drug | Treatment Arm |
| ValsartanValsartan 40mg once a day, up-titrating to 80 or maximum 160 mg to achieve target systolic blood pressure below 140mmHg, over a duration of 52 weeks. If necessary, amlodipine and/or hydrochlorothiazide may be added to achieve target systolic blood pressure. | Drug | Controlled Arm |
Primary outcome
Fibrosis volume
Time frame: 52 weeks
A difference in terms of change in interstitial volume from baseline following 52 weeks of treatment. Extracellular volume fraction (ECV) will be quantified from native and post-contrast myocardial T1. Fibrosis volume is defined as ECV x myocardial volume and indexed to body surface area (ml/m2)
2 secondary outcomes
Left ventricular mass measured on CMR
Time frame: 52 weeks
Biomarker/biochemistry
Time frame: 52 weeks
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 26 Jun 2025.
- Derived from this study: PubMed 37674806Lee V, Zheng Q, Toh DF, Pua CJ, Bryant JA, Lee CH, Cook SA, Butler J, Diez J, Richards AM, Le TT, Chin CWL. Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocol. Front Cardiovasc Med. 2023 Aug 22;10:1248468. doi: 10.3389/fcvm.2023.1248468. eCollection 2023.
- Individual participant dataSharing planned: No
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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 2 study testing Entresto and Valsartan in people with Hypertensive Heart Disease, run by National Heart Centre Singapore at 1 site in Singapore.
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 2 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 26 Jun 2025. 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 Singapore. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Fibrosis volume (time frame: 52 weeks). 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 NCT03553810, 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 26 Jun 2025.