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

Quantum Genomics

Status and phase: Completed; Phase 2

Conditions: Myocardial Infarction

Treatments: Drug: Firibastat; Drug: Ramipril

Study type: Interventional

Funder types: Industry

Identifiers

NCT03715998

QGC001-2QG4

Details and patient eligibility

About

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.

Full 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]).

Enrollment: 295 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

295 participants in 3 patient groups

Group 1: firibastat 100 mg

Experimental group

Description:

Subjects will receive 50 mg firibastat BID for 2 weeks and then 100 mg BID for 10 weeks.

Treatment:

Drug: Firibastat

Group 2: firibastat 500 mg

Experimental group

Description:

Subjects will receive 250 mg firibastat BID for 2 weeks and then 500 mg BID for 10 weeks.

Treatment:

Drug: Firibastat

Group 3: ramipril 5 mg

Active Comparator group

Description:

Subjects will receive 2.5 mg ramipril BID for 2 weeks and then 5 mg BID for 10 weeks.

Treatment:

Drug: Ramipril