- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04149990
Angiotensin-Neprilysin Inhibition in Diastolic Dysfunction After AMI (ARNiAMI)
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
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Copenhagen, Denmark, 2100
- Not yet recruiting
- Department of Cardiology, Rigshospitalet
-
Contact:
- Finn Gustafsson
- Email: Finn Gustafsson <Finn.Gustafsson@regionh.dk>
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Odense, Denmark, 5000
- Recruiting
- Department of Cardiology, Odense Universityhospital
-
Contact:
- Peter Frederiksen, MD
- Phone Number: +4524672970
- Email: peter.hartmund.frederiksen@rsyd.dk
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Documented ST segment elevation or non ST- myocardial infarction according to current guidelines
- Complete revascularization
- Age ≥50 years
- LVEF ≥45% on echocardiography performed within 72 hours of the MI.
- 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).
- Signed informed consent
Exclusion Criteria:
- Intolerance towards study medication
- Permanent atrial fibrillation,
- Known history of cardiomyopathy,
- More than mild valvular heart disease,
- Severe obstructive or restrictive pulmonary disease,
- Inability to perform exercise testing,
- Inadequate acoustic windows on echocardiography,
- Ongoing treatment with an angiotensin converting enzyme inhibitor at randomization.
- Class I indication for an angiotensin converting enzyme inhibitor
- Symptomatic hypotension, a systolic blood pressure of less than 100 mm Hg at screening
- An estimated glomerular filtration rate (eGFR) below 30 ml per minute per 1.73 m2 of body-surface area at any time,
- A serum potassium level of more than 5.2 mmol per liter at screening,
- A history of hereditary or idiopathic angioedema or unacceptable side effects during receipt of angiotensin converting enzyme inhibitor or angiotensin receptor blocker
- Inability to provide informed consent
- Concomitant use of drugs containing aliskiren in patients with diabetes mellitus.
- Severe reduced liver function, biliary cirrhosis or cholestasis (Child-Pugh class C)
- Pregnant or nursing(lactating) women(see section 8.2.1 for details)
- Fertile women unless they are using a highly effective method of contraception(see section 8.2.2 for details)
Study Plan
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:
|
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
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Ischemia
- Pathologic Processes
- Necrosis
- Myocardial Ischemia
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Myocardial Infarction
- Infarction
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Angiotensin II Type 1 Receptor Blockers
- Angiotensin Receptor Antagonists
- Valsartan
- Sacubitril and valsartan sodium hydrate drug combination
Other Study ID Numbers
- Version 1.4
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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