Firibastat or Ramipril After Acute Myocardial Infarction for Prevention of Left Ventricular Dysfunction

Phase 2

Completed

• Conditions: Myocardial Infarction
• Interventions: Drug: Firibastat; Drug: Ramipril

• Registration Number: NCT03715998
• Lead Sponsor: Quantum Genomics SA

Brief Summary

This is a multicenter, randomized, double-blind, active-controlled, dose-titrating phase 2 study to evaluate the safety and efficacy of firibastat administered orally BID (2 daily doses) versus ramipril administered orally BID over 12 weeks after acute anterior MI.

Subjects will be followed for 12 weeks (over 4 study visits). A total of 294 male and female subjects with a diagnosis of first acute anterior MI will be randomized. The subjects will need to have a primary percutaneous coronary intervention (PCI) of the index MI related artery within 24 hours after MI.

Detailed Description

At Inclusion Visit (Visit 2 \[within 72 hours after acute MI\]), subjects will be randomly assigned to 1 of the following 3 treatment groups in a 1:1:1 ratio:

* Group 1: Subjects will receive 50 mg firibastat BID for 2 weeks and then 100 mg BID for 10 weeks

* Group 2: Subjects will receive 250 mg firibastat BID for 2 weeks and then 500 mg BID for 10 weeks

* Group 3: Subjects will receive 2.5 mg ramipril BID for 2 weeks and then 5 mg BID for 10 weeks

Then subjects will undergo study procedures at Titration Visit (Visit 3 \[Day 14\]), Treatment Visit (Visit 4 Day 42\]) and End-of-Treatment Visit (Visit 5 \[Day 84\]).

Study Timeline

• Study First Submitted: 2018-10-19
• Study First Submitted QC: 2018-10-19
• Study First Posted: 2018-10-23
• Study Start: 2019-06-04
• Status Verified: 2020-12
• Primary Completion: 2021-07-08
• Study Completion: 2021-07-08
• Results First Submitted: 2022-05-23
• Results First Submitted QC: 2022-05-23
• Last Update Submitted: 2022-05-23
• Results First Posted: 2023-02-27
• Last Update Posted: 2023-02-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 295

Inclusion Criteria

• Diagnosis of first acute anterior MI (ST-elevation myocardial infarction) defined as chest pain >30 minutes and ST elevation ≥0.2 mV in at least 2 consecutive electrocardiogram (ECG) leads in the anterior area (DI, aVL, V1 V6).
• Primary PCI of the index-MI-related artery within 24 hours after the MI.

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Exclusion Criteria

• Body mass index >45 kg/m².
• Subject is hemodynamically unstable or has cardiogenic shock.
• Subjects with clinical signs of HF (Kilipp III and IV).
• Systolic blood pressure <100 mmHg at inclusion visit
• Early primary PCI of the index-MI-related artery performed within 3 hours after MI.
• Subjects treated with angiotensin-converting-enzyme inhibitor (ACE I), angiotensin receptor blocker (ARB) or sacubitril/valsartan prior to the index magnetic resonance imaging. Note: if treatment was for HTN, ACE I/ARB should be stopped, and, if necessary, another therapeutic class can be prescribed for HTN. If the ACE I/ARB was prescribed for congestive HF, the subject is not considered eligible; if the ACE I/ARB prescribed for another reason cannot be stopped, the subject is not eligible for study inclusion.
• Subjects scheduled for implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy, or pacemaker within the next 3 months. If an ICD is indicated for ventricular arrhythmia during the course of the study, a life vest, when possible, should be prescribed and the ICD scheduled after study completion.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: firibastat 100 mg	Firibastat	Subjects will receive 50 mg firibastat BID for 2 weeks and then 100 mg BID for 10 weeks.
Group 2: firibastat 500 mg	Firibastat	Subjects will receive 250 mg firibastat BID for 2 weeks and then 500 mg BID for 10 weeks.
Group 3: ramipril 5 mg	Ramipril	Subjects will receive 2.5 mg ramipril BID for 2 weeks and then 5 mg BID for 10 weeks.

Primary Outcome Measures

Name	Time	Method
Left Ventricular Ejection Fraction Assessed by Cardiac Magnetic Resonance Imaging (CMRI)	84 days	Comparison of the effects of BID oral administration of 2 doses of firibastat to those of BID oral administration of ramipril on the change from Baseline in LVEF on Day 84

Secondary Outcome Measures

Name	Time	Method
N-terminal Pro B-type Natriuretic Peptide (NT proBNP)	84 days	Comparison of the effects of BID administration of firibastat and ramipril on the change from Baseline to Day 84 in N-terminal pro b-type natriuretic peptide (NT proBNP)
Left-ventricle End-systolic Volume Assessed by CMRI	84 days	Comparison of the effects of BID administration of firibastat and ramipril on the change from Baseline to Day 84 in left-ventricle end-systolic volume
Major Cardiac Event (MACE): Combined Clinical Endpoint of Cardiovascular Death, MI, and Cardiac Hospitalization	84 days	Comparison of the effects of BID administration of firibastat and ramipril on major cardiac event (MACE) over 84 days
Left-ventricle End-diastolic Volume Assessed by CMRI	84 days	Comparison of the effects of BID administration of firibastat and ramipril on the change from Baseline to Day 84 in left-ventricle end-diastolic volume

Trial Locations

Locations (7)

Central Hospital of Hungarian Army; 🇭🇺 Budapest, Hungary

Krakowski Szpital Specjalistyczny im. Jana Pawła II; 🇵🇱 Kraków, Poland

NUSCH Bratislava Dpt. of Acute Cardiology; 🇸🇰 Bratislava, Slovakia

Hospital La Paz,; 🇪🇸 Madrid, Spain

UKSH Kiel; 🇩🇪 Kiel, Germany

Freeman Hospital Newcastle upon Tyne; 🇬🇧 Newcastle, United Kingdom

Groupe Hospitalier Pitie-Salpêtrière - Institut de Cardiologie; 🇫🇷 Paris, France