Early Treatment of ARNI on Myocardial Remodeling and Progress in Patients With Post-AMI (EARLYmyo-CRPⅠ)
Trial Snapshot
- Phase
- Phase 4
- Sponsor
- RenJi Hospital
- Enrollment
- 280
- Locations
- 1
- Primary Endpoint
- Peak Oxygen Pulse (O2-Pulse)
Study Overview
Brief Summary
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.
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Acute myocardial infarction (AMI) within 1 months prior to recruitment;
- •Aged 18 years or over and under 80 years;
- •Randomized patients will have been hemodynamically stable, SBP ≥100mmHg, no symptomatic hypotension;
- •NYHA Class Ⅱ-Ⅳ, HFrEF or HFpEF;
- •Elevated NT-proBNP or BNP at the time of screening;
- •Peak VO2/kg<16 ml/kg/min by CPET
Exclusion Criteria
- •Inability to complete a CPET;
- •Symptomatic hypotension and/or systolic blood pressure <100mmHg;
- •eGFR < 30 mL/min/1.73m2 and/or serum potassium >5.2mmol/L;
- •History of hypersensitivity or allergy to ACE-inhibitors/ARB
- •History of angioedema;
- •Pregnancy, planning pregnancy, or breast feeding;
- •Life-threatening diseases with limited life expectancy <1 year
Arms & Interventions
Experimental: sacubitril/valsartan
sacubitril/valsartan will be applied from 25mg b.i.d to 100mg b.i.d. for 3 months
Intervention: sacubitril/valsartan (Drug)
Experimental: sacubitril/valsartan
sacubitril/valsartan will be applied from 25mg b.i.d to 100mg b.i.d. for 3 months
Intervention: Cardiopulmonary Exercise Test (Other)
Experimental: sacubitril/valsartan
sacubitril/valsartan will be applied from 25mg b.i.d to 100mg b.i.d. for 3 months
Intervention: Echocardiogram (Other)
Active Comparator: perindopril
perindopril will be applied from 2mg q.d, to 8mg q.d for 3 months
Intervention: perindopril (Drug)
Active Comparator: perindopril
perindopril will be applied from 2mg q.d, to 8mg q.d for 3 months
Intervention: Cardiopulmonary Exercise Test (Other)
Active Comparator: perindopril
perindopril will be applied from 2mg q.d, to 8mg q.d for 3 months
Intervention: Echocardiogram (Other)
Outcomes
Primary Outcomes
Peak Oxygen Pulse (O2-Pulse)
Time Frame: 3 months
Difference in the interval change from baseline in peak O2-Pulse at 3 months following sacubitril/valsartan or perindopril.
LVEF
Time Frame: 3 months
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.
Peak oxygen consumption (VO2)/kg
Time Frame: 3 months
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.
Secondary Outcomes
- Peak VO2/kg change(6 months)
- Ventilatory efficiency (VE/VCO2 slope) change(6 months)
- N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) change(Baseline, 3, 6 months)
- Peak Oxygen Pulse change(6 months)
- LVEF change(6 months)
- The MOS item short form health survey, SF-36(baseline and 6 months)