Angiotensin-neprilysin blockage after myocardial infarctio

Phase 1

• Conditions: Diastolic dysfunction after acute myocardial infarction; MedDRA version: 20.1Level: LLTClassification code 10076396Term: Heart failure with preserved ejection fractionSystem Organ Class: 100000004849; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2017-002020-25-DK
• Lead Sponsor: Odense University Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-05-18
• Last Update Posted: 19 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Key inclusion criteria:
1. Documented ST segment or non ST segment elevation AMI,
2. Complete revascularization.
3. Age >=50 years
4. LVEF >=45% on echocardiography performed within 72 hours of the AMI.
5. Diastolic dysfunction defined as: Ratio of early diastolic peak mitral inflow velocity (E) to early mitral annulus diastolic velocity (e’) ratio > 8 and LA dilatation (LA volume
index>34 mL/m2).
6. Signed informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 66

Exclusion Criteria

1. Known history of cardiomyopathy, and or moderate/severe valvular heart disease,
2. Severe obstructive or restrictive pulmonary disease,
3. Inability to perform exercise testing/ inadequate acoustic windows on echocardiography,
4. Class I indication for an angiotensin converting enzyme inhibitor.
5. A systolic blood pressure of less than 100 mm Hg at screening
6. An estimated glomerular filtration rate (eGFR) below 30 ml per minute per 1.73 m2 of
body-surface area at any time,
7. A serum potassium level of more than 5.2 mmol per liter at screening,
8. A history of angioedema or unacceptable side effects during receipt of angiotensin
converting enzyme inhibitor or angiotensin receptor blocker
9. Inability to provide informed consent

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the effect of 6 months treatment with LCZ696 compared with<br>placebo on ratio of pulmonary capillary wedge pressure/cardiac index during exercise in patients with a recent AMI and Doppler echocardiographic signs of diastolic dysfunction and preserved systolic function.<br>;Secondary Objective: To assess the effect of 6 months treatment with LCZ696 compared<br>with placebo in patients with a recent AMI, diastolic dysfunction and preserved systolic function on:<br><br>1. Cardiac fibrosis assessed on cardiac magnetic resonance imaging,<br><br>2. The ST2 cardiac biomarker<br><br>3. Left atrial size and function<br>;Primary end point(s): Ratio of pulmonary capillary wedge pressure to cardiac index at peak<br>exercise after 6 months treatment with LCZ696 or placebo.<br>;Timepoint(s) of evaluation of this end point: After 26 weeks.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Amount of hyperenhancement on cardiac MRI using a semiquantitative assessment of late gadolinium hyperenhacement in a 17 segment model of the LV.<br>2. Biomarker ST2 concentration.<br>3. Left atrial volume and left atrial emptying fraction by echocardiography and MRI at rest.<br>;Timepoint(s) of evaluation of this end point: After 26 weeks.