The Role of Sacubitril/Valsartan in Post-acute Myocardial Infarction (RSVP-AMI)

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Myocardial Infarction
• Intervention / Treatment: Drug: Sacubitril / Valsartan Oral Tablet [Entresto]

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 192
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt, 21524
    • Andalusia Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sacubitril/Valsartan; 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]; 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.; Other Names: ARNI
Active Comparator: Valsartan; 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]; 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.; Other Names: ARNI

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The Young Investigator Group of Cardiovascular Research
• Investigators: Study Director: Sherif S Elbeltagui, MD, Assisstant Professor of Cardiology, University of Alexandria, Egypt

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): October 1, 2022

Study Registration Dates

• First Submitted: March 10, 2019
• First Submitted That Met QC Criteria: March 25, 2019
• First Posted (Actual): March 28, 2019

Study Record Updates

• Last Update Posted (Actual): October 6, 2022
• Last Update Submitted That Met QC Criteria: October 4, 2022
• Last Verified: October 1, 2022

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: YIG01201902

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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