Sacubitril/Valsartan vs Lifestyle in Hypertrophic Cardiomyopathy

Summary

The overall aim of this project is to establish potential benefits of a novel lifestyle (physical activity and dietary nitrate) and pharmacological (angiotensin receptor neprilysin inhibitor) interventions in patients with hypertrophic cardiomyopathy (HCM). HCM is the most common genetic cardiovascular disease with a broad spectrum of disease severity. Angiotensin receptor neprilysin inhibitor reduces death, hospitalisation, and may improve cardiac function and exercise tolerance in heart failure. Exercise training is associated with a significant increase in exercise tolerance, but appear to have limited effect on measures of cardiac morphology or function in patients with HCM. Dietary supplementation with inorganic nitrate (i.e. concentrated nitrate-rich beetroot juice) improves exercise capacity, vasodilatation and cardiac output reserves while reduces arterial wave reflections, which are linked to left ventricular diastolic dysfunction and remodelling. Using a five-centre, open label, three-arm, pilot design, the present study will evaluate the effect of lifestyle (physical activity and dietary supplementation with inorganic nitrate) and pharmacological (angiotensin receptor neprilysin inhibitor sacubitril / valsartan) interventions in patients with HCM. The Aim is to examine whether these interventions improve functional capacity, clinical phenotypic characteristics, and quality of life in patients with HCM.

Conditions

• Hypertrophic Cardiomyopathy

Interventions

BEHAVIORAL

Lifestyle

A 4-month lifestyle intervention will consist of two integrated components i.e. physical activity and dietary supplementation with inorganic nitrate. The physical activity component aims to increase daily physical activity level by at least 2000 steps/day from baseline (e.g. walking for approximately 30 minutes), at least 5-7 days per week. The second component of the lifestyle intervention is a dietary supplementation with inorganic nitrate. A single dose of inorganic nitrate given in the form of concentrated nitrate-rich beetroot juice (NO3-, BEET IT Sport, James White Drinks Ltd., Ipswich, UK) containing 6 mmol of NO3- in 70 ml bottle.

DRUG

Sacubitril/Valsartan

Angiotensin receptor neprilysin inhibitor Sacubitril / Valsartan: The treatment period begins on day 1 with initial dosing of sacubitril/valsartan, followed by uptitration every 2 to 4 weeks to the target dose of 97/103 mg twice daily. 3 doses of sacubitril/valsartan available throughout the study are 24/26 mg, 49/51 mg, and 97/103 mg, each taken by mouth twice daily. If the patient discontinues the study medication, the patient is advised to return to the clinic for an end-of-study visit. Patients undergo treatment for 4 months.

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria Careggi

  collaborator OTHER

• University Hospital Regensburg

  collaborator OTHER

• Institute of Cardiovascular Diseases, Vojvodina

  collaborator OTHER

• University of Belgrade

  collaborator OTHER

• Newcastle University

  lead OTHER

Principal Investigators

• Dr Djordje G Jakovljevic · Newcastle University Faculty of Medical Sciences, Clinical Research Facility, Newcastle upun Tyne Hospitals NHS Foundation Trust

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-05-03

Primary Completion

2022-05-15

Completion

2022-06-30

Countries

• Germany
• Italy
• Serbia
• United Kingdom

Study Locations