Angiotensin-Neprilysin Inhibition in Diastolic Dysfunction After AMI

Myocardial Infarction Clinical Trial

— ARNiAMI  

Official title:

Angiotensin-Neprilysin Inhibition in Diastolic Dysfunction After AMI

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04149990
• Other study ID #: Version 1.4
• Status: Recruiting
• Phase: Phase 2
• Start date: October 12, 2018
• Est. completion date: May 2023

Study information

• Verified date: October 2021
• Source: Odense University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study examines the effect of Entresto on central hemodynamic parameters during exercise in patients with diastolic dysfunction following acute myocardial infarction. Half of the patients will receive Entresto and the other half will receive placebo.

Description:

In patients with acute myocardial infraction (AMI) only 25-33% have entirely normal left ventricular (LV) systolic and diastolic function. Studies have show that echocardiographic signs of increased LV filling pressure (diastolic dysfunction) are associated with poor outcome after AMI. The optimal management of this group of patients is currently not known. LCZ696 is a novel combination drug consisting of two antihypertensives, sacubitril and valsartan. LCZ696 have demonstrated to reduce mortality in patients with systolic heart failure. In patients with heart failure with preserved ejection fraction a positive effect has been demonstrated on natriuretic peptides and left atrial remodelling when treated with LCZ696, further, experimental data suggest inhibition of cardiac fibrosis.

Hypothesis:

LCZ696 compared with placebo will improve central hemodynamics (reduce pulmonary capillary wedge pressure (PCWP)), and increase cardiac index (CI) during exercise in patients with diastolic dysfunction following AMI. A beneficial effect that is attributed to improved cardiac remodelling (attenuation of cardiac fibrosis).

Primary objective To asses the effect of 6 months treatment with LCZ696 compared with placebo on ratio of PCWP/CI during exercise in patients with a recent AMI and Doppler echocardiographic signs of diastolic dysfunction and preserved systolic function.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: May 2023
• Est. primary completion date: October 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

1. Documented ST segment elevation or non ST- myocardial infarction according to current guidelines

2. Complete revascularization

3. Age =50 years

4. LVEF =45% on echocardiography performed within 72 hours of the MI.

5. Diastolic dysfunction defined as: Ratio of early diastolic peak mitral inflow velocity (E) to early mitral annulus diastolic velocity (e') ratio > 8 and at least moderate LA dilatation (LA volume index>34 mL/m2).

6. Signed informed consent

Exclusion Criteria:

1. Intolerance towards study medication

2. Permanent atrial fibrillation,

3. Known history of cardiomyopathy,

4. More than mild valvular heart disease,

5. Severe obstructive or restrictive pulmonary disease,

6. Inability to perform exercise testing,

7. Inadequate acoustic windows on echocardiography,

8. Ongoing treatment with an angiotensin converting enzyme inhibitor at randomization.

9. Class I indication for an angiotensin converting enzyme inhibitor

10. Symptomatic hypotension, a systolic blood pressure of less than 100 mm Hg at screening

11. An estimated glomerular filtration rate (eGFR) below 30 ml per minute per 1.73 m2 of body-surface area at any time,

12. A serum potassium level of more than 5.2 mmol per liter at screening,

13. A history of hereditary or idiopathic angioedema or unacceptable side effects during receipt of angiotensin converting enzyme inhibitor or angiotensin receptor blocker

14. Inability to provide informed consent

15. Concomitant use of drugs containing aliskiren in patients with diabetes mellitus.

16. Severe reduced liver function, biliary cirrhosis or cholestasis (Child-Pugh class C)

17. Pregnant or nursing(lactating) women(see section 8.2.1 for details)

18. Fertile women unless they are using a highly effective method of contraception(see section 8.2.2 for details)

Related Conditions & MeSH terms

• Diastolic Dysfunction
• Infarction
• Myocardial Infarction

Intervention

Drug:
• Valsartan+ sacubitril
Treatment with Entresto(valsartan+sacubitril)
• Placebo Oral Tablet
Matching placebo treatment

Locations

Country	Name	City	State
Denmark	Department of Cardiology, Rigshospitalet	Copenhagen
Denmark	Department of Cardiology, Odense Universityhospital	Odense

Sponsors (4)

Lead Sponsor	Collaborator
Jacob Moller	Danish Heart Foundation, Odense University Hospital, Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Central hemodynamics	The primary endpoint will be the ratio of mean PCWP at peak exercise divided by cardiac index at peak exercise.	26 weeks
Secondary	cardiac MRI	Amount of hyperenhancement on cardiac MRI using a semiquantitative assessment of late gadolinium hyperenhancement in a 17 segment model of the LV.	26 weeks
Secondary	Biomarker	ST2 concentration at rest.	26 weeks
Secondary	Biomarker	MR-proANP at rest.	26 weeks
Secondary	Biomarker	NT-proBNP at rest.	26 weeks
Secondary	Echocardiographic	Left atrial volume by echocardiography and left atrial emptying fraction by echocardiography at rest.	26 weeks
Secondary	Echocardiographic	Proportion of patients with moderate or severe diastolic dysfunction at rest.echocardiography at rest.	26 weeks