Role of ARNi in Ventricular Remodeling in Hypertensive LVH

Phase 2

Recruiting

• Conditions: Hypertensive Heart Disease
• Interventions: Drug: Entresto; Drug: Valsartan

• Registration Number: NCT03553810
• Lead Sponsor: National Heart Centre Singapore

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-04-04
• Study First Submitted QC: 2018-05-30
• Study First Posted: 2018-06-12
• Study Start: 2019-04-12
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-10
• Last Update Posted: 2023-05-11
• Primary Completion: 2023-12-01
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Entresto	Entresto (valsartan/sacubitril) 100mg once a day
Controlled Arm	Valsartan	Valsartan 40mg once a day

Primary Outcome Measures

Name	Time	Method
Fibrosis volume	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)

Secondary Outcome Measures

Name	Time	Method
Biomarker/biochemistry	52 weeks	Identify potential markers as indicators of cardiac structural effects of ARNi and ARB
Left ventricular mass measured on CMR	52 weeks	Changes from baseline in left ventricular mass, indexed to body surface area (g/m2).

Trial Locations

Locations (1)

National Heart Centre Singapore; 🇸🇬 Singapore, Singapore