A Double-blind Study to Investigate Efficacy, Safety and Tolerability of BAY 1142524 in Patients After Acute Myocardial Infarction With Left-ventricular Dysfunction

NCT ID: NCT02976467

Last Updated: 2019-09-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-30
• Study Completion Date: 2018-09-04

Brief Summary

The purpose of the trial is the analysis of safety and efficacy of the chymase inhibitor BAY1142524 at a dose of 25 mg BID in comparison to placebo using a 6 months treatment period in patients with left-ventricular (LV) dysfunction after myocardial infarction (MI). BAY1142524 or placebo will be given on top of evidence-based standard of care for left-ventricular dysfunction after myocardial infarction. Primary objective is the analysis of first signs of efficacy as determined by favourable changes in functional parameters of adverse cardiac remodelling (i.e. endsystolic and enddiastolic volume index, ejection fraction). Secondary objective is the analysis of safety and tolerability as evidenced by the incidence and severity of adverse events. 30 patients have to complete treatment with verum and 30 patients have to complete treatment with placebo.

Conditions

Myocardial Infarction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Fulacimstat (BAY1142524)

30 patients with left-ventricular dysfunction after acute myocardial infarction

Group Type: EXPERIMENTAL

Fulacimstat (BAY1142524)

Intervention Type: DRUG

25 mg BAY 1142524 are given twice daily over a treatment period of 6 months

Placebo

30 patients with left-ventricular dysfunction after acute myocardial infarction

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo tablets are given twice daily over a treatment period of 6 months

Interventions

Fulacimstat (BAY1142524)

25 mg BAY 1142524 are given twice daily over a treatment period of 6 months

Intervention Type: DRUG

Placebo

Matching placebo tablets are given twice daily over a treatment period of 6 months

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with first ST elevation myocardial infarction (STEMI) treated with primary percutaneous intervention (PCI) or thrombolysis within 24 hours after symptom onset
• Diagnosis of STEMI requires the presence of the following three criteria:

• Typical clinical symptoms such as chest pain, shortness of breath for more than 20 minutes related to the myocardial infarction
• New ST elevation indicating myocardial infarction
• Significant elevation in troponin T or I with at least one value above the 99th percentile upper reference limit (URL) and/or elevation creatine kinase (CK) and creatine kinase MB (6-10% of total CK)
• At the screening period, on day 5 to 9 after MI, patients have to have a LVEF ≤ 45% and an infarct size >10% LV mass (as measured by LGE-MRI, central-blinded evaluation)

Exclusion Criteria

• Contraindication to perform contrast-enhanced cardiac MRI
• LVEF < 20%
• History of heart failure or LVEF < 50% before occurrence of the first STEMI
• Infarct size > 45% (g/g; LV mass) between 5 and 9 days after myocardial infarction
• NYHA (New York Heart Association) class IV at randomization
• Any planned cardiac intervention after baseline MRI or any other planned operations
• Non-ischemic causes for cardiomyopathy
• Diagnosis of atrial fibrillation
• Systolic blood pressure < 100 mm Hg or > 180 mm Hg; diastolic blood pressure < 50 mm Hg or >110 mm Hg, heart rate < 50 or >100 beat/minute; mean of triplicate values at randomization
• Clinically relevant hepatic dysfunction

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Kladno, , Czechia

Prague, , Czechia

Prague, , Czechia

Prague, , Czechia

Prague, , Czechia

Hanover, Lower Saxony, Germany

Dortmund, North Rhine-Westphalia, Germany

Erfurt, Thuringia, Germany

Berlin, , Germany

Beersheba, , Israel

Haifa, , Israel

Jerusalem, , Israel

Jerusalem, , Israel

Petah Tikva, , Israel

Tel Aviv, , Israel

Bergamo, Lombardy, Italy

Brescia, Lombardy, Italy

Milan, Lombardy, Italy

Milan, Lombardy, Italy

Monza-Brianza, Lombardy, Italy

Babio - Beade, Pontevedra, Spain

Barcelona, , Spain

Madrid, , Spain

Madrid, , Spain

Valencia, , Spain

Countries

Czechia; Germany; Israel; Italy; Spain

References

Duengen HD, Kim RJ, Zahger D, Orvin K, Kornowski R, Admon D, Kettner J, Shimony A, Otto C, Becka M, Kanefendt F, Romo AI, Hasin T, Ostadal P, Rojas GC, Senni M; GROUP investigators of the CHIARA MIA 2 trial. Effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute myocardial infarction-Results of the Chymase Inhibitor in Adverse Remodeling after Myocardial Infarction (CHIARA MIA) 2 trial. Am Heart J. 2020 Jun;224:129-137. doi: 10.1016/j.ahj.2020.01.012. Epub 2020 Jan 25.

Reference Type: DERIVED

PMID: 32375104 (View on PubMed)

Other Identifiers

2016-002167-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

16673

Identifier Type: -

Identifier Source: org_study_id