Clinical trial NCT02976467: A Double-blind Study to Investigate Efficacy, Safety and Tolerability of BAY 1142524 in Patients After Acute Myocardial Infarction With Left-ventricular Dysfunction
Official title: A Randomized, Double-blind, Multicenter Study to Assess the Safety and Efficacy of a 6 Month Oral Treatment With the Chymase Inhibitor BAY 1142524 at a Dose of 25 mg BID in Comparison to Placebo on Top of Standard of Care in Patients With Reduced Left-ventricular Ejection Fraction (LVEF≤ 45%) After Acute Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myocardial Infarction
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2016-11-29
Enrollment: 107
Sex: ALL
Minimum age (years): 40
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in left-ventricular ejection fraction (LVEF)
timeFrame: At 6 months
measure: Change in end diastolic volume index (EDVI)
timeFrame: At 6 months
measure: Change in end systolic volume index (ESVI)
timeFrame: At 6 months
Secondary outcomes:
measure: Number of patients with adverse events
timeFrame: Up to 7 months
measure: Number of patients with serious adverse events
timeFrame: Up to 7 months
Other outcomes:
Locations:
city: Kladno
country: Czechia
city: Praha 10
country: Czechia
city: Praha 4
country: Czechia
city: Praha 5
country: Czechia
city: Praha 5
country: Czechia
city: Hannover
country: Germany
state: Niedersachsen
city: Dortmund
country: Germany
state: Nordrhein-Westfalen
city: Erfurt
country: Germany
state: Thüringen
city: Berlin
country: Germany
city: Beer Sheva
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Jerusalem
country: Israel
city: Petah Tikva
country: Israel
city: Tel Aviv
country: Israel
city: Bergamo
country: Italy
state: Lombardia
city: Brescia
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Monza-Brianza
country: Italy
state: Lombardia
city: Babio - Beade
country: Spain
state: Pontevedra
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: 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.