Clinical trial NCT03715998: Firibastat or Ramipril After Acute Myocardial Infarction for Prevention of Left Ventricular Dysfunction
Official title: A Phase 2, Double-blind, Active-controlled, Dose-titrating Efficacy and Safety Study of Firibastat Compared to Ramipril Administered Orally, Twice Daily, Over 12 Weeks to Prevent Left Ventricular Dysfunction After Acute MI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myocardial Infarction
Lead sponsor: Quantum Genomics SA
Sponsor class: INDUSTRY
First posted: 2018-10-23
Enrollment: 295
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 \[Day 84\]).

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Left Ventricular Ejection Fraction Assessed by Cardiac Magnetic Resonance Imaging (CMRI)
timeFrame: 84 days
Secondary outcomes:
measure: Left-ventricle End-diastolic Volume Assessed by CMRI
timeFrame: 84 days
measure: Left-ventricle End-systolic Volume Assessed by CMRI
timeFrame: 84 days
measure: Major Cardiac Event (MACE): Combined Clinical Endpoint of Cardiovascular Death, MI, and Cardiac Hospitalization
timeFrame: 84 days
measure: N-terminal Pro B-type Natriuretic Peptide (NT proBNP)
timeFrame: 84 days
Other outcomes:
Locations:
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpêtrière - Institut de Cardiologie
city: Kiel
country: Germany
facility: UKSH Kiel
city: Budapest
country: Hungary
facility: Central Hospital of Hungarian Army
city: Kraków
country: Poland
facility: Krakowski Szpital Specjalistyczny im. Jana Pawła II
city: Bratislava
country: Slovakia
facility: NUSCH Bratislava Dpt. of Acute Cardiology
city: Madrid
country: Spain
facility: Hospital La Paz,
city: Newcastle
country: United Kingdom
facility: Freeman Hospital Newcastle upon Tyne
Study officials:
affiliation: Groupe Hospitalier Pitié-Salpêtrière - Paris
name: Gilles Montalescot, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Khosla J, Aronow WS, Frishman WH. Firibastat: An Oral First-in-Class Brain Aminopeptidase A Inhibitor for Systemic Hypertension. Cardiol Rev. 2022 Jan-Feb 01;30(1):50-55. doi: 10.1097/CRD.0000000000000360.