Role of ARNi in Ventricular Remodeling in Hypertensive LVH

NCT03553810 | Completed Phase 2 DMC

• 1 other identifier: 2018/2182
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• 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)

  52 weeks

Secondary Outcomes (2)

• Left ventricular mass measured on CMR

  52 weeks

• Biomarker/biochemistry

  52 weeks

Study Arms (2)

Treatment Arm

EXPERIMENTAL

Entresto (valsartan/sacubitril) 100mg once a day

Drug: Entresto

Controlled Arm

ACTIVE COMPARATOR

Valsartan 40mg once a day

Drug: Valsartan

Interventions

Entresto DRUG

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.

Also known as: Valsartan/sacubitril

Treatment Arm

Valsartan DRUG

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.

Controlled Arm

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Increased left ventricular mass on cardiovascular magnetic resonance (based on established local age- and sex-specific CMR ranges)
• Essential hypertension

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• National Heart Centre Singapore: lead
• National Medical Research Council (NMRC), Singapore: collaborator

Study Sites (1)

National Heart Centre Singapore

Singapore, 169609, Singapore

Location

Related Publications (1)

• 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.

  PMID: 37674806 DERIVED

MeSH Terms

Interventions

sacubitril and valsartan sodium hydrate drug combination; Valsartan

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2018
• First Posted: June 12, 2018
• Study Start: April 12, 2019
• Primary Completion: June 28, 2024
• Study Completion: June 28, 2024
• Last Updated: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)