Asymptomatic (New York Heart Association =2) left ventricular systolic dysfunction (defined as ejection fraction =40% measured by Simpson's biplane using transthoracic echocardiography) at least 3 months post myocardial infarction MedDRA version: 20.0 Level: LLT Classification code 10019279 Term: Heart failure System Organ Class: 10007541 - Cardiac disorders MedDRA version: 20.1 Level: LLT Classification code 10064079 Term: Heart failure NYHA class I System Organ Class: 10007541 - Cardiac dis
Conditions
Interventions
Trade Name: Entresto
Product Name: Entresto
Pharmaceutical Form: Tablet
INN or Proposed INN: Sacubitril/Valsartan
CAS Number: 149709-62-6
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
NHS Greater Glasgow and Clyde
University of Glasgow
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Acute myocardial infarction at least 3 months prior to recruitment • Left ventricular ejection fraction = 40% as measured by transthoracic echocardiography • Ability to provide written, informed consent • Age =18 years • Tolerance of a minimum dose of ACE inhibitor/ARB (ramipril 2.5mg BD or equivalent) • Treatment with a beta-blocker unless not tolerated or contraindicated. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: • Contraindication to CMR (ferrous prosthesis, implantable cardiac device or severe claustrophobia) • Clinical and/or radiological heart failure (NYHA=2) • Symptomatic hypotension and/or systolic blood pressure 5.2mmol/L • Persistent/permanent atrial fibrillation • History of AMI within last 3 months • History of hypersensitivity or allergy to ACE-inhibitors/ARB • History of angioedema • Known hypersensitivity to the active study drug substances, contrast media or any of the excipients • Obesity (where body girth exceeds MRI scanner diameter) • Pregnancy, planning pregnancy, or breast feeding • Inability to give informed consent or comply with study protocol • Evidence of hepatic disease as determined by any one of the following: AST or ALT values exceeding 2 x ULN at Visit 1, history of hepatic encephalopathy, history of oesophageal varices, or history of portacaval shunt • History of biliary cirrhosis and cholestasis • Active treatment with cholestyramine or colestipol resins • Active treatment with lithium or direct renin inhibitor • Participation in another intervention study involving a drug or device within the past 90 days (co-enrolment in observational studies is permitted)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effect of sacubitril/valsartan, compared to the current standard of care, valsartan, on heart structure and function in patients who have sustained heart muscle damage following a heart attack. ;Secondary Objective: To examine the mechanism of action of sacubitril/valsartan using blood tests which measure levels of proteins and enzymes in the blood and how they relate to heart muscle damage following a heart attack.;Primary end point(s): The primary endpoint is the change in indexed left ventricular end-systolic volume (LVESVI), from baseline to 12 months, based on cardiac magnetic resonance imaging measurements. ;Timepoint(s) of evaluation of this end point: Week 0 and week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in other cardiac magnetic resonance imaging based metrics (indexed LV end-diastolic volume, LVEF, LV mass) of LV remodelling from baseline to 12 months. • Changes in blood markers of LV remodelling (sST2, Galectin 3, TIMP-1, MMP-9, hsTnT, Type III Procollagen Peptide [PIIINP] and GDF-15) from baseline to 12 months • Changes in neurohormonal levels (N-terminal A- and B- type natriuretic peptides, C-terminal ANP, CNP, adrenomedullin, cGMP, renin, aldosterone, endothelin-1 and neprilysin activity) from baseline to 12 months. ;Timepoint(s) of evaluation of this end point: Week 0, week 26 and week 52 | — |
Countries
United Kingdom
Contacts
Public ContactMaureen Travers
NHS Greater Glasgow and Clyde
Outcome results
None listed