REVERSE-LVH: Role of ARNi in Ventricular Remodeling in Hypertensive LVH

Sponsor

National Heart Centre Singapore (Other)

Overall Status

Recruiting

CT.gov ID

NCT03553810

Collaborator

National Medical Research Council (NMRC), Singapore (Other)

100

Enrollment

Location

Arms

56.6

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypertensive Heart Disease	Drug: Entresto Drug: Valsartan	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Role of ARNi in Ventricular Remodeling in Hypertensive LVH

Actual Study Start Date :

Apr 12, 2019

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm Entresto (valsartan/sacubitril) 100mg once a day	Drug: Entresto 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. Other Names: Valsartan/sacubitril
Active Comparator: Controlled Arm Valsartan 40mg once a day	Drug: Valsartan 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.

Arm

Intervention/Treatment

Experimental: Treatment Arm

Entresto (valsartan/sacubitril) 100mg once a day

Drug: Entresto

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.

Other Names:

Valsartan/sacubitril

Active Comparator: Controlled Arm

Valsartan 40mg once a day

Drug: Valsartan

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.

Outcome Measures

Primary Outcome Measures

Fibrosis volume [52 weeks]
Changes from baseline in fibrosis volume measured on CMR. 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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Heart Centre Singapore	Singapore		Singapore	169609

Sponsors and Collaborators

National Heart Centre Singapore
National Medical Research Council (NMRC), Singapore

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

National Heart Centre Singapore

ClinicalTrials.gov Identifier:

NCT03553810

Other Study ID Numbers:

2018/2182

First Posted:

Jun 12, 2018

Last Update Posted:

Apr 26, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Heart Diseases

Ventricular Remodeling

Valsartan

Sacubitril and valsartan sodium hydrate drug combination

Study Results

No Results Posted as of Apr 26, 2022