The Role of Sacubitril/Valsartan in Post-acute Myocardial Infarction

Study Overview
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Brief Summary
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Sacubitril/Valsartan (SAC/VAL) is a new treatment of congestive heart failure (CHF) recently indicated as class I, level of evidence B in the recent European Society of Cardiology (ESC) guidelines 2016 of CHF. PARADIGM-HF trial demonstrated a significant improvement of morbidity and mortality with SAC/VAL in comparison to enalapril. So far, no data available about the effect of usage of SAC/VAL post-acute myocardial infarction (AMI) except in animal experimental models. The purpose of the research is evaluation of the effects of SAC/VAL in post-AMI in comparison to the traditional Angiotensin Converting Enzyme inhibitors (ACEs inhibitors) or Angiotensin II Receptor Blockers (ARBs) in a real-life clinical trial in treatment of post-AMI patients with reduced left ventricular (LV) systolic function.

Detailed Description
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Background and study rationale: Sacubitril/Valsartan (SAC/VAL) is now approved by the U.S. Food and Drug Administration (FDA) for heart failure with reduced ejection fraction (HFrEF) and also, recently indicated as class I indication, level of evidence B in the European Society of Cardiology (ESC) guidelines 2016 on congestive heart failure (CHF).(1) PARADIGM-HF trial demonstrated that morbidity and mortality can be improved with SAC/VAL In comparison to enalapril, it reduced the occurrence of cardiovascular death or hospitalization for CHF by 20% with a 16% reduction in all-cause mortality.(2) So far, no available data about the effect of usage of SAC/VAL in post-AMI except in animal experimental models that proved efficacy of SAC/VAL in preventing AMI-induced LV dysfunction compared with SAC/VAL, also significantly attenuated LV scar size following AMI compared with placebo .(3) Aim of the work: This study aims to investigate the effects of SAC/VAL in post-AMI through using it instead of conventional Angiotensin Converting enzyme inhibitors (ACEs inhibitors) or Angiotensin II Receptor Blockers (ARBs) in treatment of post-AMI patients with reduced left ventricular (LV) systolic function. Design: Randomized open label interventional clinical trial.

Official Title
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The Role of Sacubitril/Valsartan in Post-acute Myocardial Infarction: The RSVP-AMI Trial

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Drug: Sacubitril / Valsartan Oral Tablet [Entresto]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Post-AMI patients who underwent successful PPCI and LVEF ≤40%. Exclusion Criteria: Post-AMI patients who underwent successful PPCI and LVEF >40%. History of hypersensitivity or allergy to any of the study drugs, as well as known or suspected contraindications to the study drugs. Symptomatic hypotension and/or an SBP < 100 mmHg. Estimated GFR < 30 mL/min/1.73m2 as measured by the simplified MDRD formula or serum potassium > 5.2 mmol/L.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sacubitril/Valsartan<br>In successfully revascularized post-AMI patients with LVEF ≤40% Sacubitril/Valsartan with the recommended starting dose: 24 mg/26 mg PO BID. After 2-4 weeks, the dose will be doubled to the target maintenance dose of 97 mg/103 mg PO BID (if tolerated) for 6 months. | Drug: Sacubitril / Valsartan Oral Tablet [Entresto]<br>* Sacubitril/Valsartan with the recommended starting dose: 24 mg/26 mg PO BID. After 2-4 weeks, the dose will be doubled to the target maintenance dose of 97 mg/103 mg PO BID (if tolerated) for 6 months.<br>* Other names: ARNI;|
| Active Comparator: Valsartan<br>In successfully revascularized post-AMI patients with LVEF ≤40% Valsartan with an initial dose of 40 mg PO BID, with subsequent titrations to target maintenance dose of 160 mg BID as tolerated. | Drug: Sacubitril / Valsartan Oral Tablet [Entresto]<br>* Sacubitril/Valsartan with the recommended starting dose: 24 mg/26 mg PO BID. After 2-4 weeks, the dose will be doubled to the target maintenance dose of 97 mg/103 mg PO BID (if tolerated) for 6 months.<br>* Other names: ARNI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One week major adverse cerebrovascular and cardiovascular events (MACCE) | Major adverse cerebrovascular and cardiovascular events (MACCE) will be assessed 1 week after AMI | 1 week after AMI | 
| Twenty four weeks major adverse cerebrovascular and cardiovascular events (MACCE) | Major adverse cerebrovascular and cardiovascular events (MACCE) will be assessed 24 weeks after AMI | 24 weeks after AMI | 
| Change in the ejection fraction during hospital stay, 3 months and 6 months after AMI. | Change in the ejection fraction assessed by transthoracic echocardiography assessment (TTE) during hospital stay, 3 months and 6 months after AMI. | In hospital, 3 months and 6 months after AMI |