Myocardial InfarctionPhase 2ARNiAMINCT04149990
Angiotensin-Neprilysin Inhibition in Diastolic Dysfunction After AMI
A Phase 2 study testing Entresto Pill in people with Myocardial Infarction and Diastolic Dysfunction, run by Jacob Moller at 2 sites in Denmark.
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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Myocardial Infarction, Diastolic Dysfunction
- What is being tested?
- Entresto Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 2 sitesDenmark
- Study dates
- 12 Oct 2018to 6 Jun 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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,
Show all 18Show fewer
- 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)
Trial locations and contacts
2 sites in 1 country.
Denmark2 sites
Department of Cardiology, Rigshospitalet
Copenhagen, 2100
Department of Cardiology, Odense Universityhospital
Odense, 5000
About this study
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.
Read the 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.
- Conditions
- Myocardial Infarction, Diastolic Dysfunction
- Being tested
- Entresto Pill
- Medical subject headings
- Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Entresto PillDrug
Also called Valsartan+ sacubitril
NO other interventions
| Study group | Role | What they receive |
|---|---|---|
| Entresto | Active comparator | Combination of valsartan and sacubitril titrated to 103+97 mg B.I.D. for 26 weeks Receives: Drug: Entresto Pill |
| Placebo | Placebo comparator | Matching placebo B.I.D. for 26 weeks Receives: Drug: Entresto Pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
Central hemodynamics
The primary endpoint will be the ratio of mean PCWP at peak exercise divided by cardiac index at peak exercise.
Measured: 26 weeks
Secondary outcomes (6)
cardiac MRI
Amount of hyperenhancement on cardiac MRI using a semiquantitative assessment of late gadolinium hyperenhancement in a 17 segment model of the LV.
Measured: 26 weeks
Biomarker 1
ST2 concentration at rest.
Measured: 26 weeks
Biomarker 2
MR-proANP at rest.
Measured: 26 weeks
Biomarker 3
NT-proBNP at rest.
Measured: 26 weeks
Echocardiographic 1
Left atrial volume by echocardiography and left atrial emptying fraction by echocardiography at rest.
Measured: 26 weeks
Echocardiographic 2
Proportion of patients with moderate or severe diastolic dysfunction at rest.echocardiography at rest.
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2019
- Study start12 Oct 2018
- Primary completion6 Jul 2022
- Study completion6 Jun 2023
Why it stopped: Low recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myocardial InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jacob Moller
- Sponsor type
- University, hospital or other
- Collaborators
- Danish Heart Foundation, Odense University Hospital, Copenhagen University Hospital, Rigshospitalet
- Responsible party
- Sponsor-investigator, Jacob Moller, Odense University Hospital
- Investigators
- Peter Hartmund Frederiksen, DMSC, Principal investigator, Odense University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04149990
- Sponsor's protocol ID
- Version 1.4
- Acronym
- ARNiAMI
- Status last verified
- Jan 2025
- First submitted
- 31 Oct 2019
- Last updated
- 29 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Angiotensin-Neprilysin Inhibition in Diastolic Dysfunction After AMI
- ClinicalTrials.gov ID
- NCT04149990
- Acronym / sponsor ID
- ARNiAMI / Version 1.4
- Conditions
- Myocardial Infarction, Diastolic Dysfunction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Jacob MollerUniversity, hospital or other
- Collaborators
- Danish Heart Foundation, Odense University Hospital, Copenhagen University Hospital, Rigshospitalet
- Study start
- 12 Oct 2018 (actual)
- Primary completion
- 6 Jul 2022 (actual)
- Study completion
- 6 Jun 2023 (actual)
- First posted
- 4 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Entresto | Active comparator | Drug: Entresto PillCombination of valsartan and sacubitril titrated to 103+97 mg B.I.D. for 26 weeks |
| Placebo | Placebo comparator | Drug: Entresto PillMatching placebo B.I.D. for 26 weeks |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (18 listed)
- Intolerance towards study medication
- Permanent atrial fibrillation,
- Known history of cardiomyopathy,
- More than mild valvular heart disease,
- Severe obstructive or restrictive pulmonary disease,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Entresto PillAlso: Valsartan+ sacubitrilNO other interventions | Drug | Entresto, Placebo |
Primary outcome
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.
6 secondary outcomes
cardiac MRI
Time frame: 26 weeks
Biomarker 1
Time frame: 26 weeks
Biomarker 2
Time frame: 26 weeks
Biomarker 3
Time frame: 26 weeks
Echocardiographic 1
Time frame: 26 weeks
Echocardiographic 2
Time frame: 26 weeks
Results and safety
The study was stopped early (reason given: Low recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Hartmund Frederiksen, DMSC principal investigator
Odense University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Entresto Pill in people with Myocardial Infarction and Diastolic Dysfunction, run by Jacob Moller at 2 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Central hemodynamics (time frame: 26 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2025.