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.
Drug: Bendavia (MTP-131)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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. ] [ Designated as safety issue: No ]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. ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
- 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. ] [ Designated as safety issue: No ]Bendavia levels will be obtained.
- Comparison between treatment groups of the myocardial infarct size [ Time Frame: Day 30+7 ] [ Designated as safety issue: Yes ]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. ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
- 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|
|Estimated Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
|Active Comparator: Bendavia™||
Drug: Bendavia (MTP-131)
|Placebo Comparator: Placebo||
Identically appearing placebo
|Contact: Tom Wytrzymalski, MD||847-235-5226|
|United States, Florida|
|Advanced Medical Research Center||Withdrawn|
|Port Orange, Florida, United States, 32127|
|United States, Michigan|
|Henry Ford Hospital||Recruiting|
|Detroit, Michigan, United States, 48202|
|Principal Investigator: Akshay Khandelwal|
|United States, Nebraska|
|Creighton Cardiac Center||Recruiting|
|Omaha, Nebraska, United States, 68131|
|Contact: Sandy Byers 402-280-4934 Sandybyers@creighton.edu|
|Principal Investigator: Michael Del Core|
|Universitätsmedizin Berlin, Charité Campus Benjamin Franklin||Recruiting|
|Berlin, Germany, 12203|
|Principal Investigator: Bernhard Witzenbichler|
|Staedtische Kliniken Bielefeld||Recruiting|
|Bielefeld, Germany, 33604|
|Principal Investigator: Christoph Stellbrink|
|Marienhaus Klinikum Eifel||Recruiting|
|Bitburg, Germany, 54634|
|Principal Investigator: Rainer Zotz|
|Freiburg, Germany, 79095|
|Principal Investigator: Ingo Ahrens|
|Herford, Germany, 32049|
|Principal Investigator: Jan Kaehler|
|Stuttgart, Germany, 70376|
|Principal Investigator: Tim Schaeufele|
|Helios Klinikum Wuppertal, Herzzentrum Elberfeld||Recruiting|
|Wuppertal, Germany, 42117|
|Principal Investigator: Klaus Tiroch|
|Semmelweis Egyetem Kardiológiai Központ, Városmajor u. 68||Recruiting|
|Budapest, Hungary, 1122|
|Contact: György Bárczi 0036 1 4586840|
|Principal Investigator: Bela Merkely|
|Honvédkórház-Állami Egészségügyi Központ||Recruiting|
|Budapest, Hungary, 1134|
|Principal Investigator: Robert Kiss|
|Gottsegen Gyorgy Orszagos Kardiologiai Intezet||Recruiting|
|Budapest, Hungary, 1096|
|Principal Investigator: Zsolt Piroth|
|PTE Klinikai Központ Szívgyógyászati Klinika||Recruiting|
|Pecs, Hungary, H-7624|
|Principal Investigator: Tamas Simor|
|Szent György Kórház, II. Belgyógyászati Osztály||Recruiting|
|Szekesfehervar, Hungary, H-8000|
|Principal Investigator: Laszlo Toth|
|Zala Megyei Kórház, Kardiológiai Osztály, Zrínyi Miklós út 1.||Recruiting|
|Zalaegerszeg, Hungary, H-8900|
|Contact: Gyöngyi Nagy 0036 92 507 500 ext 1436 email@example.com|
|Principal Investigator: Geza Lupkovics|
|Krakowski Szpital Specjalistyczny im. Jana Pwla II, Centrum Interwencyjnego Leczenia Chorob Serca i Naczyn z Pododdzialem Kariologii Interwencyjnej||Recruiting|
|ul. Pradnicka 80, Krakow, Poland, 31-202|
|Contact: Jacek Godlewski 0048 12 614 35 01 firstname.lastname@example.org|
|Principal Investigator: Jacek Godlewski|
|Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, Pracownia Kardiologii Inwazyjnej||Recruiting|
|ul. Banacha 1A, Warsaw, Poland, 02-097|
|Contact: Adam Rdzanek 0048 22 599 18 08|
|Principal Investigator: Janusz Kochman|
|Medical University of Bialystok||Not yet recruiting|
|Bialystok, Poland, 15-276|
|Principal Investigator: Slawomir Dobrzycki, MD|
|SPSK Nr 7 Klaskiego Uniwersytetu Medycznego w Katowicach, Gornoslaskie Centrum Medyczne im. Prof. Leszka Gieca, III Oddzial Kardiologii, Zklad Kardiologii Inwazjnejul, Ziolowa 45-47||Recruiting|
|Katowice, Poland, 40-635|
|Contact: Sebastian Dworowy email@example.com|
|Principal Investigator: Ochala Andrzej|
|SPSK Nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach, Gornoslaskie Centrum Medyczne im. Prof. Leszaka Gieca, I Oddzial Kardiologii, ul. Ziolowa 45-47||Recruiting|
|Katowice, Poland, 40-635|
|Contact: Grazyna Wachala 0048 32 359 88 90|
|Principal Investigator: Krystian Wita|
|Wojewodzki Szpital Zespolony w Kielcach, Swietokrzyskie Centrum Kardiologii||Recruiting|
|Kielce, Poland, 25-736|
|Principal Investigator: Marianna Janion|
|Wojewodzki Specjalistyczny Szpital im WI. Bieganskiego, II Katedra i Klinika Kardiologii Uniwersytetu Medycznego w Lodzi, Pracownia Kardiologii Inwazyinej, ul. Kniaziewicza 1/5||Recruiting|
|Lodz, Poland, 91-347|
|Contact: Tomasz Jezewski 0048 601 142 625 firstname.lastname@example.org|
|Principal Investigator: Jan Peruga|
|SP ZOZ Wojewodzkie Centrum Medyczne, Zaklad Diagnostyki Obrazowej, AI. W. Witosa 26||Recruiting|
|Opole, Poland, 45-418|
|Contact: Elbieta Gola 0048 77 4520 344 email@example.com|
|Principal Investigator: Wladyslaw Pluta|
|Centrum Kardiologii Inwazyjnej, Elektroterapii i Angiologii||Recruiting|
|Oswiecim, Poland, 32-600|
|Principal Investigator: Stanislaw Bartus|
|Szpital Bielanski im. ks. Jerzego Popieluszki||Recruiting|
|Warsaw, Poland, 01-809|
|Principal Investigator: Marek Dabrowski|
|Instytut Kardiologii im. Prymasa Tysiaclecia Stefana Kardynala Wyszynskiego||Recruiting|
|Warsaw, Poland, 04-628|
|Principal Investigator: Zbigniew Chmielak|
|Wojewodzki Szpital Specjalistyczny we Wroclawiu, Oddzial Kardiologiczny, ul. H. Kamieskiego 73a||Recruiting|
|Wroclaw, Poland, 51-124|
|Contact: Lucyna Lenartowska 0048 71 327 05 30 ext 328 firstname.lastname@example.org|
|Principal Investigator: Jerzy Lewczuk|
|Dolnoslaski Szpital Specjalistyczny im. T. Marciniaka, Centrum Medycyny Ratunkowe||Recruiting|
|Wroclaw, Poland, 50-420|
|Principal Investigator: Krystyna Loboz-Grudzien|
|Samodzielny Publiczny Szpital Wojewodzki im. Papieza Jana Pawla II w Zamosciu, Oddzial Kardiologii z Pododdzialem Intensywnej Terapil Kardiologicznej, ul. Aleje Jana Pawta II 10||Recruiting|
|Zamosc, Poland, 22-400|
|Contact: Tomasz Smyk 0048 84 677 38 90|
|Principal Investigator: Andrzej Kleinrok|
|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|