Back to resultsFiribastat or Ramipril After Acute Myocardial Infarction for Prevention of Left Ventricular Dysfunction (QUORUM)
Primary Purpose
Myocardial Infarction
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ramipril
Firibastat
Sponsored by
About this trial
This is an interventional treatment trial for Myocardial Infarction
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.
Sites / Locations
- Groupe Hospitalier Pitie-Salpêtrière - Institut de Cardiologie
- UKSH Kiel
- Central Hospital of Hungarian Army
- Krakowski Szpital Specjalistyczny im. Jana Pawła II
- NUSCH Bratislava Dpt. of Acute Cardiology
- Hospital La Paz,
- Freeman Hospital Newcastle upon Tyne
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Group 1: firibastat 100 mg
Group 2: firibastat 500 mg
Group 3: ramipril 5 mg
Arm Description
Subjects will receive 50 mg firibastat BID for 2 weeks and then 100 mg BID for 10 weeks.
Subjects will receive 250 mg firibastat BID for 2 weeks and then 500 mg BID for 10 weeks.
Subjects will receive 2.5 mg ramipril BID for 2 weeks and then 5 mg BID for 10 weeks.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
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
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)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03715998
Brief Title
Firibastat or Ramipril After Acute Myocardial Infarction for Prevention of Left Ventricular Dysfunction
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
June 4, 2019 (Actual)
Primary Completion Date
July 8, 2021 (Actual)
Study Completion Date
July 8, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Quantum Genomics SA
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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]).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Infarction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
295 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1: firibastat 100 mg
Arm Type
Experimental
Arm Description
Subjects will receive 50 mg firibastat BID for 2 weeks and then 100 mg BID for 10 weeks.
Arm Title
Group 2: firibastat 500 mg
Arm Type
Experimental
Arm Description
Subjects will receive 250 mg firibastat BID for 2 weeks and then 500 mg BID for 10 weeks.
Arm Title
Group 3: ramipril 5 mg
Arm Type
Active Comparator
Arm Description
Subjects will receive 2.5 mg ramipril BID for 2 weeks and then 5 mg BID for 10 weeks.
Intervention Type
Drug
Intervention Name(s)
Ramipril
Intervention Description
1 or 2 capsules administered orally, twice daily
Intervention Type
Drug
Intervention Name(s)
Firibastat
Other Intervention Name(s)
QGC001
Intervention Description
1 or 2 capsules administered orally, twice daily
Primary Outcome Measure Information:
Title
Left Ventricular Ejection Fraction Assessed by Cardiac Magnetic Resonance Imaging (CMRI)
Description
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
Time Frame
84 days
Secondary Outcome Measure Information:
Title
Left-ventricle End-diastolic Volume Assessed by CMRI
Description
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
Time Frame
84 days
Title
Left-ventricle End-systolic Volume Assessed by CMRI
Description
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
Time Frame
84 days
Title
Major Cardiac Event (MACE): Combined Clinical Endpoint of Cardiovascular Death, MI, and Cardiac Hospitalization
Description
Comparison of the effects of BID administration of firibastat and ramipril on major cardiac event (MACE) over 84 days
Time Frame
84 days
Title
N-terminal Pro B-type Natriuretic Peptide (NT proBNP)
Description
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)
Time Frame
84 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilles Montalescot, MD, PhD
Organizational Affiliation
Groupe Hospitalier Pitié-Salpêtrière - Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Groupe Hospitalier Pitie-Salpêtrière - Institut de Cardiologie
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
UKSH Kiel
City
Kiel
Country
Germany
Facility Name
Central Hospital of Hungarian Army
City
Budapest
Country
Hungary
Facility Name
Krakowski Szpital Specjalistyczny im. Jana Pawła II
City
Kraków
Country
Poland
Facility Name
NUSCH Bratislava Dpt. of Acute Cardiology
City
Bratislava
Country
Slovakia
Facility Name
Hospital La Paz,
City
Madrid
Country
Spain
Facility Name
Freeman Hospital Newcastle upon Tyne
City
Newcastle
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33027067
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.
Results Reference
derived
Learn more about this trial
Firibastat or Ramipril After Acute Myocardial Infarction for Prevention of Left Ventricular Dysfunction
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