Sacubitril/Valsartan vs Lifestyle in Hypertrophic Cardiomyopathy

• Status: Recruiting
• Trial end date: 2022-06-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Newcastle University
• Collaborators: Assistance Publique - Hôpitaux de Paris; Azienda Ospedaliero-Universitaria Careggi; Institute for Cardiovascular Diseases of Vojvodina; University Hospital Regensburg; University of Belgrade
• Treatments: LCZ 696; Valsartan

Criteria

Inclusion Criteria:

• Confirmed diagnosis of obstructive and/or non-obstructive hypertrophic cardiomyopathy.

• Agreement to be a participant in the study protocol and willing/able to return for follow-up.

• Able to provide written informed consent

Exclusion Criteria:

• Less than 3 months post septal reduction therapy (surgery or catheter based intervention)

• Clinical decompensation in the previous 3 months, defined as New York Heart Association class IV congestive heart failure symptoms.

• Resting blood pressure greater than 180/100 mm Hg.

• Systolic blood pressure lower than 100 mmHg

• Hypotensive response to exercise testing (≥20 mmHg decrease of systolic blood pressure from baseline blood pressure or an initial increase in systolic blood pressure followed by a decrease of systolic blood pressure ≥20 mmHg).

• Use of angiotensin converting Enzyme inhibitors or angiotensin receptor blockers.

• Resting left ventricular outflow tract gradient > 50 mm Hg.

• Left ventricular ejection fraction of less than 50% by echocardiography.

• Implanted pacemaker or cardiodefibrilator in the last 3 months or scheduled.

• Renal insufficiency with a glomerular filtration rate of less than 30 mL/min per 1.73m2.

• Present or planned pregnancy.

• Life expectancy less than 12 months.

• Body mass index >40 kg/m2.

• A history of exercise induced syncope or ventricular arrhythmias.

• Inability to exercise due to orthopaedic or other non-cardiovascular limitations.

• Use of other investigational drugs at the time of enrolment.

• Any surgical or medical condition that in the opinion of the investigator may place the patient at higher risk from his/her participation in the study or is likely to prevent the patient from complying with the requirements of the study or completing the study.

• History or presence of any other disease with a life expectancy of <3 years

• History of noncompliance to medical regimens and patients who are considered potentially unreliable.

• History or evidence of drug or alcohol abuse within the past 12 months.

• History of malignancy of any organ system (other than localized basal or squamous cell carcinoma of the skin or localized prostate cancer), treated or untreated, within the past 2 years, regardless of whether there is evidence of local recurrence or metastases.

• Life-threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and AF or atrial flutter with a resting ventricular rate >110 beats per minute.

• Participation in competitive or organized sport activities (such as football, basketball, rugby, hockey, etc), burst activity (such as sprinting, racket sports, etc) or heavy isometric exercise (such as body building or bench-pressing) or opposition of refraining from the same for the duration of the study.