Early Treatment of ARNI on Myocardial Remodeling and Progress

Early Treatment of ARNI on Myocardial Remodeling and Progress in Patients With Post-AMI (EARLYmyo-CRPⅠ)

Myocardial remodeling following myocardial infarction (MI) is an important prognostic factor for heart function and adverse cardiovascular events, especially are intimately linked with heart failure. MI often causes deleterious changes in ventricular size, shape, and function. This adverse remodeling and progress is mediated by neurohormonal and hemodynamic alterations. The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan was shown to be superior to an ACE inhibitor in patients with heart failure with reduced ejection fraction (HF-REF), reduce the risk of both death (from cardiovascular and all-causes) and heart failure hospitalization, may be a new approach to the treatment of heart failure. However, the impact of early treatment of ARNI on myocardial remodeling and progress, and aerobic exercise capacity in patients with prior MI has yet to be assessed. The aim of this study is to evaluate the efficacy and the safety of early treatment of ARNI on myocardial remodeling and progress, and aerobic exercise capacity in patients following MI.

Study Overview

• Status: Unknown
• Conditions: Myocardial Infarction
• Intervention / Treatment: Drug: sacubitril/valsartan; Other: Cardiopulmonary Exercise Test; Other: Echocardiogram; Drug: perindopril

Detailed Description

Myocardial remodeling following myocardial infarction (MI) is an important prognostic factor for heart function and adverse cardiovascular events. The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan was shown to reduce the risk of both death (from cardiovascular and all-causes) and heart failure hospitalization. However, whether early treatment of ARNI following post-MI could alter myocardial remodeling or aerobic exercise capacity has yet to be assessed. The patients with MI within one month were enrolled in the treatment of ARNI group or ACEI group. The study proposes to perform serial Cardiopulmonary Exercise Tests (CPET) to prospectively measure changes in aerobic exercise capacity in patients with prior myocardial infarction (MI), echocardiographic measures of LV end-diastolic/ systolic volumes, LV ejection fraction (LVEF), BNP and protein plasma levels, symptomatic heart failure, and life quality.

• Study Type: Interventional
• Enrollment (Anticipated): 280
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Qin Shao, M.D,Ph.D; Phone Number: 86-21-68385225; Email: shaoqindr@126.com
• Study Contact Backup: Name: Jun Ma, M.D,Ph.D; Phone Number: 86-21-68383164; Email: drjunma@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Renji Hospital, Shanghai Jiaotong University, School of Medicine
      • Contact: Qin Shao, M.D,Ph.D; Phone Number: 86-21-68385225; Email: shaoqindr@126.com
      • Contact: Jun Ma, M.D,Ph.D; Phone Number: 86-21-68383164; Email: drjunma@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Acute myocardial infarction (AMI) within 1 months prior to recruitment;
2. Aged 18 years or over and under 80 years;
3. Randomized patients will have been hemodynamically stable, SBP ≥100mmHg, no symptomatic hypotension;
4. NYHA Class Ⅱ-Ⅳ, HFrEF or HFpEF;
5. Elevated NT-proBNP or BNP at the time of screening;
6. Peak VO2/kg<16 ml/kg/min by CPET

Exclusion Criteria:

1. Inability to complete a CPET;
2. Symptomatic hypotension and/or systolic blood pressure <100mmHg;
3. eGFR < 30 mL/min/1.73m2 and/or serum potassium >5.2mmol/L;
4. History of hypersensitivity or allergy to ACE-inhibitors/ARB
5. History of angioedema;
6. Pregnancy, planning pregnancy, or breast feeding;
7. Life-threatening diseases with limited life expectancy <1 year

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: sacubitril/valsartan; sacubitril/valsartan will be applied from 25mg b.i.d to 100mg b.i.d. for 3 months	Drug: sacubitril/valsartan; sacubitril/valsartan will be applied from 25mg/b.i.d for 1-2 weeks,50mg b.i.d for 2 weeks, to target dosage 100mg b.i.d for 3 months unless severe safety outcome occurs; Other: Cardiopulmonary Exercise Test; All patients will undergo a first CPET prior to initiation of treatment, a second one after 3 months, and a third one after 6 months of treatment.; Other Names: CPET; Other: Echocardiogram; An echocardiogram (ultrasound of the heart) will be performed prior to initiation of treatment and then again 3 months, 6 months later.; Other Names: ECHO
Active Comparator: Active Comparator: perindopril; perindopril will be applied from 2mg q.d, to 8mg q.d for 3 months	Other: Cardiopulmonary Exercise Test; All patients will undergo a first CPET prior to initiation of treatment, a second one after 3 months, and a third one after 6 months of treatment.; Other Names: CPET; Other: Echocardiogram; An echocardiogram (ultrasound of the heart) will be performed prior to initiation of treatment and then again 3 months, 6 months later.; Other Names: ECHO; Drug: perindopril; Drug: perindopril will be applied from 2mg for q.d for 1-2 weeks, 4mg q.d 2 weeks, to target dosage 8mg q.d for 3 months unless severe safety outcome occur

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak oxygen consumption (VO2)/kg	Difference in the interval change from baseline in peak VO2/kg at 3 months following sacubitril/valsartan from 25mg/b.i.d, 50mg b.i.d, to target dosage 100mg b.i.d for 3 months, when compared with the interval change in perindopril from 2mg q.d, 4mg q.d, to target dosage 8mg q.d for 3 months.	3 months
Peak Oxygen Pulse (O2-Pulse)	Difference in the interval change from baseline in peak O2-Pulse at 3 months following sacubitril/valsartan or perindopril.	3 months
LVEF	Difference in the interval changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV) by echocardiography assessment at 3 months, comparing sacubitril/valsartan with perindopril.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak VO2/kg change	Difference in the interval changes from baseline and 6 months in peak VO2 comparing sacubitril/valsartan with perindopril.	6 months
Peak Oxygen Pulse change	Difference in the interval changes from baseline and 6 months in peak O2-Pulse comparing sacubitril/valsartan with perindopril.	6 months
Ventilatory efficiency (VE/VCO2 slope) change	Difference in the interval changes from baseline and 6 months in the VE/VCO2 slope comparing sacubitril/valsartan with perindopril.	6 months
LVEF change	Difference in the interval changes from baseline in LVEF, LVESV, and left LVEDV at 6 months, comparing sacubitril/valsartan with perindopril.	6 months
N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) change	Change in concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to 3 months , 6 months.	Baseline, 3, 6 months
The MOS item short form health survey, SF-36	A 36-item short-form (SF-36) was constructed to survey health status in the Medical Outcomes Study. The SF-36 was designed for use in clinical practice and research, health policy evaluations, and general population surveys. The SF-36 includes one multi-item scale that assesses eight health concepts. The higher scores mean a better outcome.	baseline and 6 months

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Study Chair: Qin Shao, M.D,Ph.D, Renji Hospital; Study Director: Jun Ma, M.D,Ph.D, Renji Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2020
• Primary Completion (Anticipated): May 1, 2021
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: April 8, 2020
• First Submitted That Met QC Criteria: April 8, 2020
• First Posted (Actual): April 13, 2020

Study Record Updates

• Last Update Posted (Actual): April 14, 2020
• Last Update Submitted That Met QC Criteria: April 12, 2020
• Last Verified: March 1, 2020

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; Enzyme Inhibitors; Protease Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Valsartan; Sacubitril and valsartan sodium hydrate drug combination; Perindopril
• Other Study ID Numbers: CRP

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