Early Treatment of ARNI on Myocardial Remodeling and Progress
Primary Purpose
Myocardial Infarction
Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
sacubitril/valsartan
perindopril
Cardiopulmonary Exercise Test
Echocardiogram
Sponsored by

About this trial
This is an interventional treatment trial for Myocardial Infarction
Eligibility Criteria
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
Sites / Locations
- RenJi Hospital, Shanghai JiaoTong University, School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Experimental: sacubitril/valsartan
Active Comparator: perindopril
Arm Description
sacubitril/valsartan will be applied from 25mg b.i.d to 100mg b.i.d. for 3 months
perindopril will be applied from 2mg q.d, to 8mg q.d for 3 months
Outcomes
Primary Outcome Measures
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.
Peak Oxygen Pulse (O2-Pulse)
Difference in the interval change from baseline in peak O2-Pulse at 3 months following sacubitril/valsartan or perindopril.
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.
Secondary Outcome Measures
Peak VO2/kg change
Difference in the interval changes from baseline and 6 months in peak VO2 comparing sacubitril/valsartan with perindopril.
Peak Oxygen Pulse change
Difference in the interval changes from baseline and 6 months in peak O2-Pulse comparing sacubitril/valsartan with perindopril.
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.
LVEF change
Difference in the interval changes from baseline in LVEF, LVESV, and left LVEDV at 6 months, comparing sacubitril/valsartan with perindopril.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04342351
Brief Title
Early Treatment of ARNI on Myocardial Remodeling and Progress
Official Title
Early Treatment of ARNI on Myocardial Remodeling and Progress in Patients With Post-AMI (EARLYmyo-CRPⅠ)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Unknown status
Study Start Date
May 1, 2020 (Anticipated)
Primary Completion Date
May 1, 2021 (Anticipated)
Study Completion Date
December 30, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RenJi Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Infarction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
280 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental: sacubitril/valsartan
Arm Type
Experimental
Arm Description
sacubitril/valsartan will be applied from 25mg b.i.d to 100mg b.i.d. for 3 months
Arm Title
Active Comparator: perindopril
Arm Type
Active Comparator
Arm Description
perindopril will be applied from 2mg q.d, to 8mg q.d for 3 months
Intervention Type
Drug
Intervention Name(s)
sacubitril/valsartan
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
perindopril
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Cardiopulmonary Exercise Test
Other Intervention Name(s)
CPET
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Echocardiogram
Other Intervention Name(s)
ECHO
Intervention Description
An echocardiogram (ultrasound of the heart) will be performed prior to initiation of treatment and then again 3 months, 6 months later.
Primary Outcome Measure Information:
Title
Peak oxygen consumption (VO2)/kg
Description
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.
Time Frame
3 months
Title
Peak Oxygen Pulse (O2-Pulse)
Description
Difference in the interval change from baseline in peak O2-Pulse at 3 months following sacubitril/valsartan or perindopril.
Time Frame
3 months
Title
LVEF
Description
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.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Peak VO2/kg change
Description
Difference in the interval changes from baseline and 6 months in peak VO2 comparing sacubitril/valsartan with perindopril.
Time Frame
6 months
Title
Peak Oxygen Pulse change
Description
Difference in the interval changes from baseline and 6 months in peak O2-Pulse comparing sacubitril/valsartan with perindopril.
Time Frame
6 months
Title
Ventilatory efficiency (VE/VCO2 slope) change
Description
Difference in the interval changes from baseline and 6 months in the VE/VCO2 slope comparing sacubitril/valsartan with perindopril.
Time Frame
6 months
Title
LVEF change
Description
Difference in the interval changes from baseline in LVEF, LVESV, and left LVEDV at 6 months, comparing sacubitril/valsartan with perindopril.
Time Frame
6 months
Title
N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) change
Description
Change in concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to 3 months , 6 months.
Time Frame
Baseline, 3, 6 months
Title
The MOS item short form health survey, SF-36
Description
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.
Time Frame
baseline and 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qin Shao, M.D,Ph.D
Phone
86-21-68385225
Email
shaoqindr@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jun Ma, M.D,Ph.D
Phone
86-21-68383164
Email
drjunma@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qin Shao, M.D,Ph.D
Organizational Affiliation
RenJi Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jun Ma, M.D,Ph.D
Organizational Affiliation
RenJi Hospital
Official's Role
Study Director
Facility Information:
Facility Name
RenJi Hospital, Shanghai JiaoTong University, School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200127
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qin Shao, M.D,Ph.D
Phone
86-21-68385225
Email
shaoqindr@126.com
First Name & Middle Initial & Last Name & Degree
Jun Ma, M.D,Ph.D
Phone
86-21-68383164
Email
drjunma@126.com
12. IPD Sharing Statement
Plan to Share IPD
No
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Early Treatment of ARNI on Myocardial Remodeling and Progress
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