Angiotensin-Neprilysin Inhibition in Diastolic Dysfunction After AMI (ARNiAMI)

October 6, 2021 updated by: Jacob Moller
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.

Study Overview

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Entresto
Combination of valsartan and sacubitril titrated to 103+97 mg B.I.D. for 26 weeks
Treatment with Entresto(valsartan+sacubitril)
Other Names:
  • Entresto
Placebo Comparator: Placebo
Matching placebo B.I.D. for 26 weeks
Matching placebo treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Central hemodynamics
Time Frame: 26 weeks
The primary endpoint will be the ratio of mean PCWP at peak exercise divided by cardiac index at peak exercise.
26 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
cardiac MRI
Time Frame: 26 weeks
Amount of hyperenhancement on cardiac MRI using a semiquantitative assessment of late gadolinium hyperenhancement in a 17 segment model of the LV.
26 weeks
Biomarker
Time Frame: 26 weeks
ST2 concentration at rest.
26 weeks
Biomarker
Time Frame: 26 weeks
MR-proANP at rest.
26 weeks
Biomarker
Time Frame: 26 weeks
NT-proBNP at rest.
26 weeks
Echocardiographic
Time Frame: 26 weeks
Left atrial volume by echocardiography and left atrial emptying fraction by echocardiography at rest.
26 weeks
Echocardiographic
Time Frame: 26 weeks
Proportion of patients with moderate or severe diastolic dysfunction at rest.echocardiography at rest.
26 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 12, 2018

Primary Completion (Anticipated)

October 1, 2022

Study Completion (Anticipated)

May 1, 2023

Study Registration Dates

First Submitted

October 31, 2019

First Submitted That Met QC Criteria

October 31, 2019

First Posted (Actual)

November 4, 2019

Study Record Updates

Last Update Posted (Actual)

October 14, 2021

Last Update Submitted That Met QC Criteria

October 6, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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