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

Myocardial Infarction Clinical Trial

— QUORUM  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03715998
• Other study ID #: QGC001-2QG4
• Status: Completed
• Phase: Phase 2
• Start date: June 4, 2019
• Est. completion date: July 8, 2021

Study information

• Verified date: December 2020
• Source: Quantum Genomics SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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]).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 295
• Est. completion date: July 8, 2021
• Est. primary completion date: July 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• Ventricular Dysfunction
• Ventricular Dysfunction, Left

Intervention

Drug:
• Ramipril
1 or 2 capsules administered orally, twice daily
• Firibastat
1 or 2 capsules administered orally, twice daily

Locations

Country	Name	City	State
France	Groupe Hospitalier Pitie-Salpêtrière - Institut de Cardiologie	Paris
Germany	UKSH Kiel	Kiel
Hungary	Central Hospital of Hungarian Army	Budapest
Poland	Krakowski Szpital Specjalistyczny im. Jana Pawla II	Kraków
Slovakia	NUSCH Bratislava Dpt. of Acute Cardiology	Bratislava
Spain	Hospital La Paz,	Madrid
United Kingdom	Freeman Hospital Newcastle upon Tyne	Newcastle

Sponsors (1)

Lead Sponsor	Collaborator
Quantum Genomics SA

Countries where clinical trial is conducted

France,  Germany,  Hungary,  Poland,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Left Ventricular Ejection Fraction Assessed by Cardiac Magnetic Resonance Imaging (CMRI)	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	84 days
Secondary	Left-ventricle End-diastolic Volume Assessed by CMRI	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	84 days
Secondary	Left-ventricle End-systolic Volume Assessed by CMRI	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	84 days
Secondary	Major Cardiac Event (MACE): Combined Clinical Endpoint of Cardiovascular Death, MI, and Cardiac Hospitalization	Comparison of the effects of BID administration of firibastat and ramipril on major cardiac event (MACE) over 84 days	84 days
Secondary	N-terminal Pro B-type Natriuretic Peptide (NT proBNP)	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)	84 days