PERI-STEMI: The Effects of Sacubitril-Valsartan vs Enalapril on Left Ventricular Remodeling in ST-elevation Myocardial Infarction

Sponsor

West China Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04912167

Collaborator

(none)

376

Enrollment

Location

Arms

Anticipated Duration (Months)

6.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of the PERI-STEMI trial is to assess whether sacubitril-valsartan is more effective in preventing adverse LV remodeling for patients with ST-elevation myocardial infarction (STEMI) than enalapril.

Condition or Disease	Intervention/Treatment	Phase
STEMI	Drug: Sacubitril-Valsartan Drug: Enalapril Drug: Valsartan	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

376 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Multi-center, Prospective Randomized Controlled Trial on the Effects of Sacubitril-Valsartan vs Enalapril on Left Ventricular Remodeling in ST-elevation Myocardial Infarction

Anticipated Study Start Date :

Nov 1, 2021

Anticipated Primary Completion Date :

Mar 1, 2022

Anticipated Study Completion Date :

Jun 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ARNI-Sacubitril-Valsartan patients randomized to angiotensin receptor neprilysin inhibitor (ARNI) group will receive 2 doses of angiotensin receptor blocker (ARB) to ensure a minimum 36-hour washout period prior to initiation of ARNI therapy, and then be started with the first dose or sacubitril-valsartan.	Drug: Sacubitril-Valsartan After initiation of the treatment of sacubitril/valsartan, the dose of the medicine will be titrated to a target level based on the systolic blood pressure of the patients. (24/26 mg, 49/51 mg and 97/103 mg, twice daily) Drug: Valsartan For patients who were previously treated with ACEI and receiving the last dose of that agent during the last 36 hours prior to randomization, Valsartan (VAL489) 40 mg and 80 mg tablets, two doses for 1 day was used.
Active Comparator: ACEI-Enalapril patients randomized to angiotensin-converting enzyme inhibitor (ACEI) group will directly start with the first dose of enalapril	Drug: Enalapril After initiation of the treatment of enalapril, the dose of the medicine will be titrated to a target level based on the systolic blood pressure of the patients. (2.5 mg, 5 mg, and 10 mg,twice daily)

Arm

Intervention/Treatment

Experimental: ARNI-Sacubitril-Valsartan

patients randomized to angiotensin receptor neprilysin inhibitor (ARNI) group will receive 2 doses of angiotensin receptor blocker (ARB) to ensure a minimum 36-hour washout period prior to initiation of ARNI therapy, and then be started with the first dose or sacubitril-valsartan.

Drug: Sacubitril-Valsartan

After initiation of the treatment of sacubitril/valsartan, the dose of the medicine will be titrated to a target level based on the systolic blood pressure of the patients. (24/26 mg, 49/51 mg and 97/103 mg, twice daily)

Drug: Valsartan

For patients who were previously treated with ACEI and receiving the last dose of that agent during the last 36 hours prior to randomization, Valsartan (VAL489) 40 mg and 80 mg tablets, two doses for 1 day was used.

Active Comparator: ACEI-Enalapril

patients randomized to angiotensin-converting enzyme inhibitor (ACEI) group will directly start with the first dose of enalapril

Drug: Enalapril

After initiation of the treatment of enalapril, the dose of the medicine will be titrated to a target level based on the systolic blood pressure of the patients. (2.5 mg, 5 mg, and 10 mg,twice daily)

Outcome Measures

Primary Outcome Measures

LV remodeling index on CMR [6 months]
change of the indexed LV mass (Δ LVmassi) from baseline to 6-month follow-up on CMR

Secondary Outcome Measures

left ventricular (LV) ejection fraction [6 months]
left ventricular ejection fraction indexes at the 6-month CMR.
global peak LV longitudinal strain [6 months]
global peak LV longitudinal strain at the 6-month CMR.
myocardial fibrosis [6 months]
extracelluar volume measured through T1 mapping sequence at the 6-month CMR.
Time to the first occurrence of a composite endpoint of adverse clinical events [up to approximately 60 months]
including all deaths (cardiac death vs non-cardiac death), non-fatal myocardial re-infarction, hospitalization for worsening heart failure or need for advanced HF therapies (hospital stay > 24 hours)(e.g., intravenous use of inotropes, left ventricular assist device placement, or cardiac transplantation)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Aged between 18 - 75 years old
First-time ST-segment elevation myocardial infarction based on the newest ESC guidelines
Timely primary percutaneous coronary intervention within 12 hours from onset
Written informed consent acquired

Exclusion Criteria:

Known history of or persistent clinical chronic heart failure prior to randomization
Previous use of ARNI, or intolerance or contraindications to study drugs including ARNI or ACEI
History of significant chronic coronary obstruction and adverse ventricular remodeling
History of any cardiomyopathy, valvular heart disease, congenital heart disease, stent or CABG, or planned open-heart surgery within 3 months
History of hepatic impairment or history of cirrhosis with evidence of portal hypertension
History of chronic renal dysfunction, or eGFR < 30 ml/min/1.73 m2
History of malignancy and with a life span less than one year
Patients with a known history of angioedema related to previous ACEIs/ARB therapy.
With contraindication to MRI examination (pacemaker and claustrophobia) or cannot finish breath-holding when lying on the examination bed
Pregnancy or nursing women