Evaluation of Myocardial Effects of Bendavia for Reducing Reperfusion Injury in Patients With Acute Coronary Events (EMBRACE)
The purpose of this research study is to assess the effectiveness, safety and tolerability of an investigational drug, called Bendavia, on reducing the area of heart muscle affected by a myocardial infarction (heart attack) in participants who have undergone successful coronary intervention (heart treatment) and stenting.
Participation in the study is due to last for approximately 7 months. It is planned that up to 300 participants will take part in the study from centers in the United States and around the world.
|Reperfusion Injury STEMI||Drug: Bendavia (MTP-131) Drug: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
|Official Title:||A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety, Tolerability and Efficacy of Intravenous Bendavia (MTP-131) on Reperfusion Injury in Patients Treated With Standard Therapy Including Primary PCI and Stenting for ST-segment Elevation Myocardial Infarction|
- Comparison between treatment groups of the infarct size measured by the area under the creatine kinase-MB (CK-MB)enzyme curve. [ Time Frame: Immediately after the PCI procedure and then at 6, 12, 24, 36, 48, 60, and 72 hours after the PCI. ]Comparison is calculated from measurements from the central clinical chemistry laboratory obtained over the initial 72 hours following the initial PCI procedure from samples drawn.
- Comparison between treatment groups of the measurement of the cardiac infarct size calculated by the area under the troponin I enzyme curve. [ Time Frame: Immediately after the PCI procedure and then at 6, 12, 24, 36, 48, 60, and 72 hours after the PCI. ]Comparison between treatment groups of the measurement of the cardiac infarct size calculated by the area under the troponin I enzyme curve calculated from measurements from the central clinical chemistry laboratory obtained over the initial 72 hours following the initial PCI procedure from samples drawn.
- Comparison between treatment groups of the measurement of the cardiac infarct size calculated by the volume of infarcted myocardium. [ Time Frame: Day 4±1 ]Comparison between treatment groups of the measurement of the cardiac infarct size calculated by the volume of infarcted myocardium (late contrast gadolinium enhancement) on the day 4±1 cardiac MRI using a 1.5-Tesla body MRI scanner. The gadolinium enhancement will be defined quantitatively by the amount of tissue exhibiting an intensity of the myocardial post-contrast signal that is more than 2 standard deviations above that in a reference region of remote, non-infarcted myocardium within the same slice.
- Comparison between treatment groups of the infarct size as measured by the ratio of the volume of infarcted myocardium to the volume of edematous myocardium. [ Time Frame: Day 4±1 ]The volume of infarcted myocardium will be measured as the volume of tissue exhibiting late contrast gadolinium enhancement. This will be defined quantitatively by an intensity of the myocardial post-contrast signal that is more than 2 standard deviations above that in a reference region of remote, non-infarcted myocardium within the same slice. Standard extracellular gadolinium-based contrast agents will be used at a dose of 0.2 mmol/kg. The 2D inversion recovery prepared fast gradient echo sequences will be used.
- Comparison between treatment groups of the degree and incidence of "no-reflow". [ Time Frame: Day 4±1 and 30+7 ]Ranked in the order of priority by: The size of microvascular dysfunction, the ratio of the volume of microvascular dysfunction to the volume of ischemia, the incidence of patients with TIMI perfusion grade 3 flow after completion of the PCI, the corrected TIMI frame count at completion of the PCI, and the relative amount of ST-segment elevation resolution from the pre-PCI electrocardiogram (ECG) to the immediately post-PCI and 24-hour post-PCI ECGs.
- Comparison between treatment groups of the myocardial function and structure. [ Time Frame: Day 4±1 and Day 30+7 ]
Cardiac MRI by:
- The left ventricular (LV) ejection fraction,
- The LV end diastolic volume,
- The LV end systolic volume,
- The modified Hochman Choo expansion index is calculated, in which wall thicknesses are measured at the midpoint of the infarct and the septum and the sections with the thinnest infarct and most marked cavity dilation will be used for each patient. Total heart area is the cross-sectional area of the heart with left ventricle included; this ratio of dilation was used to correct for variations in patient and heart sizes.
- Comparison between treatment groups of the incidence of immediate myocardial complications. [ Time Frame: 24 hours post-PCI ]
- Sustained ventricular tachycardia or ventricular fibrillation requiring medical intervention.
- Q waves on ECG at 24 hours post-PCI.
- Mechanical complications including Free wall rupture, Ventricular septal defect and Ischemic mitral regurgitation.
- Emergency use of nitroprusside, calcium channel blocker or adenosine administration during the PCI procedure.
- The pharmacokinetics of Bendavia in acute STEMI. [ Time Frame: 1, 3, 6, 12, 24, 36, 48 and 60 hours after completion of the PCI. ]Bendavia levels will be obtained.
- Comparison between treatment groups of the myocardial infarct size [ Time Frame: Day 30+7 ]The volume of infarcted myocardium will be calculated using late contrast gadolinium enhancement. The ratio of the volume of infarcted myocardium (late contrast gadolinium enhancement) to the volume of edematous myocardium (the ischemic volume determined by T-2 weighted images using triple inversion recovery fast spin echo sequences) will be determined. Ischemic volume will be measured by the edematous volume using T2-weighted images and a triple inversion recovery fast spin echo sequences protocol on the day 4±1 cardiac MRI.
- Comparison between treatment groups of the laboratory markers of congestive heart failure and systemic inflammation. [ Time Frame: Pre-PCI, 24 hours after PCI, 30 + 7 days after PCI, 90 ± 14 days after PCI, 6 + 1.5 months after PCI. ]
- N-terminal pro-B-Type natriuretic protein (NT-proBNP) levels measured at the central laboratory from samples obtained at various timepoints.
- High sensitivity C-reactive protein (hsCRP) levels measured at the central laboratory from samples obtained at
- Comparison between treatment groups of the comparative impact of Bendavia through 30 days and 6 months on the incidence of the composite endpoint. [ Time Frame: Through 30 days and 6 months ]
Comparison includes the following events:
- Death (all causes).
- New onset CHF beginning >24 hours after PCI but within the duration of the index hospitalization.
- CHF re-hospitalization after discharge from index hospitalization to 6 months later.
- Comparison between treatment groups of renal function. [ Time Frame: Through 30 days and through 6 months ]
- Serial determinations of serum creatinine, estimated GFR (using the Modified Diet Renal Disease formula), cystatin C, and BUN through 30 days.
- Serial calculations of estimated GFR (using the Modified Diet Renal Disease formula) through 30 days and through 6 months.
- Incidence of at least a grade 1 episode of contrast-induced nephropathy post-PCI, defined as an increase in serum creatinine of ≥25% of the baseline value and/or an increase in serum creatinine of 0.5 mg/dl occurring within 48 hours of receiving a radiographic contrast agent through 30 days and through 6 months.
|Study Start Date:||April 2012|
|Study Completion Date:||February 2015|
|Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
|Active Comparator: Bendavia™||
Drug: Bendavia (MTP-131)
|Placebo Comparator: Placebo||
Identically appearing placebo
Please refer to this study by its ClinicalTrials.gov identifier: NCT01572909
|United States, Florida|
|Advanced Medical Research Center|
|Port Orange, Florida, United States, 32127|
|United States, Michigan|
|Henry Ford Hospital|
|Detroit, Michigan, United States, 48202|
|United States, Nebraska|
|Creighton Cardiac Center|
|Omaha, Nebraska, United States, 68131|
|Universitätsmedizin Berlin, Charité Campus Benjamin Franklin|
|Berlin, Germany, 12203|
|Staedtische Kliniken Bielefeld|
|Bielefeld, Germany, 33604|
|Marienhaus Klinikum Eifel|
|Bitburg, Germany, 54634|
|Freiburg, Germany, 79095|
|Herford, Germany, 32049|
|Stuttgart, Germany, 70376|
|Helios Klinikum Wuppertal, Herzzentrum Elberfeld|
|Wuppertal, Germany, 42117|
|Gottsegen Gyorgy Orszagos Kardiologiai Intezet|
|Budapest, Hungary, 1096|
|Semmelweis Egyetem Kardiológiai Központ, Városmajor u. 68|
|Budapest, Hungary, 1122|
|Honvédkórház-Állami Egészségügyi Központ|
|Budapest, Hungary, 1134|
|PTE Klinikai Központ Szívgyógyászati Klinika|
|Pecs, Hungary, H-7624|
|Szent György Kórház, II. Belgyógyászati Osztály|
|Szekesfehervar, Hungary, H-8000|
|Zala Megyei Kórház, Kardiológiai Osztály, Zrínyi Miklós út 1.|
|Zalaegerszeg, Hungary, H-8900|
|Krakowski Szpital Specjalistyczny im. Jana Pwla II, Centrum Interwencyjnego Leczenia Chorob Serca i Naczyn z Pododdzialem Kariologii Interwencyjnej|
|ul. Pradnicka 80, Krakow, Poland, 31-202|
|Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, Pracownia Kardiologii Inwazyjnej|
|ul. Banacha 1A, Warsaw, Poland, 02-097|
|Medical University of Bialystok|
|Bialystok, Poland, 15-276|
|SPSK Nr 7 Klaskiego Uniwersytetu Medycznego w Katowicach, Gornoslaskie Centrum Medyczne im. Prof. Leszka Gieca, III Oddzial Kardiologii, Zklad Kardiologii Inwazjnejul, Ziolowa 45-47|
|Katowice, Poland, 40-635|
|SPSK Nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach, Gornoslaskie Centrum Medyczne im. Prof. Leszaka Gieca, I Oddzial Kardiologii, ul. Ziolowa 45-47|
|Katowice, Poland, 40-635|
|Wojewodzki Szpital Zespolony w Kielcach, Swietokrzyskie Centrum Kardiologii|
|Kielce, Poland, 25-736|
|Wojewodzki Specjalistyczny Szpital im WI. Bieganskiego, II Katedra i Klinika Kardiologii Uniwersytetu Medycznego w Lodzi, Pracownia Kardiologii Inwazyinej, ul. Kniaziewicza 1/5|
|Lodz, Poland, 91-347|
|SP ZOZ Wojewodzkie Centrum Medyczne, Zaklad Diagnostyki Obrazowej, AI. W. Witosa 26|
|Opole, Poland, 45-418|
|Centrum Kardiologii Inwazyjnej, Elektroterapii i Angiologii|
|Oswiecim, Poland, 32-600|
|Szpital Bielanski im. ks. Jerzego Popieluszki|
|Warsaw, Poland, 01-809|
|Instytut Kardiologii im. Prymasa Tysiaclecia Stefana Kardynala Wyszynskiego|
|Warsaw, Poland, 04-628|
|Dolnoslaski Szpital Specjalistyczny im. T. Marciniaka, Centrum Medycyny Ratunkowe|
|Wroclaw, Poland, 50-420|
|Wojewodzki Szpital Specjalistyczny we Wroclawiu, Oddzial Kardiologiczny, ul. H. Kamieskiego 73a|
|Wroclaw, Poland, 51-124|
|Samodzielny Publiczny Szpital Wojewodzki im. Papieza Jana Pawla II w Zamosciu, Oddzial Kardiologii z Pododdzialem Intensywnej Terapil Kardiologicznej, ul. Aleje Jana Pawta II 10|
|Zamosc, Poland, 22-400|
|Principal Investigator:||Anjan Chakrabarti, MD||Beth Israel Deaconess Medical Center, Interventional Cardiology, 185 Pilgrim Rd, Baker 4, Boston, MA 02215|
|Study Chair:||C. M. Gibson, MD||Beth Israel Deaconess Medical Center, Interventional Cardiology, 185 Pilgrim Rd, Baer 4, Boston, MA 02215|