NCT04342351

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
280

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started May 2020

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 8, 2020

Completed
5 days until next milestone

First Posted

Study publicly available on registry

April 13, 2020

Completed
18 days until next milestone

Study Start

First participant enrolled

May 1, 2020

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2021

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 30, 2021

Completed
Last Updated

April 14, 2020

Status Verified

March 1, 2020

Enrollment Period

1 year

First QC Date

April 8, 2020

Last Update Submit

April 12, 2020

Conditions

Outcome Measures

Primary Outcomes (3)

  • 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 Outcomes (6)

  • Peak VO2/kg change

    6 months

  • Peak Oxygen Pulse change

    6 months

  • Ventilatory efficiency (VE/VCO2 slope) change

    6 months

  • LVEF change

    6 months

  • N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) change

    Baseline, 3, 6 months

  • +1 more secondary outcomes

Study Arms (2)

Experimental: sacubitril/valsartan

EXPERIMENTAL

sacubitril/valsartan will be applied from 25mg b.i.d to 100mg b.i.d. for 3 months

Drug: sacubitril/valsartanOther: Cardiopulmonary Exercise TestOther: Echocardiogram

Active Comparator: perindopril

ACTIVE COMPARATOR

perindopril will be applied from 2mg q.d, to 8mg q.d for 3 months

Drug: perindoprilOther: Cardiopulmonary Exercise TestOther: Echocardiogram

Interventions

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

Experimental: sacubitril/valsartan

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

Active Comparator: perindopril

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.

Also known as: CPET
Active Comparator: perindoprilExperimental: sacubitril/valsartan

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

Also known as: ECHO
Active Comparator: perindoprilExperimental: sacubitril/valsartan

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

RenJi Hospital, Shanghai JiaoTong University, School of Medicine

Shanghai, Shanghai Municipality, 200127, China

Location

MeSH Terms

Conditions

Myocardial Infarction

Interventions

sacubitril and valsartan sodium hydrate drug combinationPerindoprilExercise TestClostridium perfringens epsilon-toxin

Condition Hierarchy (Ancestors)

Myocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular DiseasesInfarctionIschemiaPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosis

Intervention Hierarchy (Ancestors)

IndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsHeart Function TestsDiagnostic Techniques, CardiovascularDiagnostic Techniques and ProceduresDiagnosisRespiratory Function TestsDiagnostic Techniques, Respiratory SystemErgometryInvestigative Techniques

Study Officials

  • Qin Shao, M.D,Ph.D

    RenJi Hospital

    STUDY CHAIR
  • Jun Ma, M.D,Ph.D

    RenJi Hospital

    STUDY DIRECTOR

Central Study Contacts

Qin Shao, M.D,Ph.D

CONTACT

Jun Ma, M.D,Ph.D

CONTACT

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 8, 2020

First Posted

April 13, 2020

Study Start

May 1, 2020

Primary Completion

May 1, 2021

Study Completion

December 30, 2021

Last Updated

April 14, 2020

Record last verified: 2020-03

Data Sharing

IPD Sharing
Will not share

Locations