Studying the effect of medication (sacubitril/valsartan) on heart muscle damage after heart attacks

Phase 1

• Conditions: 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: 20.0Level: LLTClassification code 10019279Term: Heart failureSystem Organ Class: 10007541 - Cardiac disorders; MedDRA version: 20.1Level: LLTClassification code 10064079Term: Heart failure NYHA class ISystem Organ Class: 10007541 - Cardiac disorders; MedDRA version: 20.0Level: LLTClassification code 10069501Term: Left ventricular systolic dysfunctionSystem Organ Class: 10007541 - Cardiac disorders; MedDRA version: 20.0Level: PTClassification code 10000891Term: Acute myocardial infarctionSystem Organ Class: 10007541 - Cardiac disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2017-003460-13-GB
• Lead Sponsor: HS Greater Glasgow and Clyde

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-06-08
• Last Update Posted: 11 June 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 100

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

•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 <100mmHg
•eGFR < 30 mL/min/1.73m2 and/or serum potassium >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) 

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.<br>;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.<br>;Timepoint(s) of evaluation of this end point: Week 0 and week 52

Secondary Outcome Measures

Name	Time	Method
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.<br>•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<br>•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. <br>;Timepoint(s) of evaluation of this end point: Week 0, week 26 and week 52