Early Treatment of ARNI on Myocardial Remodeling and Progress

Myocardial Infarction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04342351
• Other study ID #: CRP
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: May 1, 2020
• Est. completion date: December 30, 2021

Study information

• Verified date: March 2020
• Source: RenJi Hospital
• Contact: Qin Shao, M.D,Ph.D
• Phone: 86-21-68385225
• Email: shaoqindr[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 280
• Est. completion date: December 30, 2021
• Est. primary completion date: May 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 ?-?, 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

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

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
• 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

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.
• Echocardiogram
An echocardiogram (ultrasound of the heart) will be performed prior to initiation of treatment and then again 3 months, 6 months later.

Locations

Country	Name	City	State
China	RenJi Hospital, Shanghai JiaoTong University, School of Medicine	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
RenJi Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Peak VO2/kg change	Difference in the interval changes from baseline and 6 months in peak VO2 comparing sacubitril/valsartan with perindopril.	6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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