Evaluation of Myocardial Effects of Bendavia for Reducing Reperfusion Injury in Patients With Acute Coronary Events (EMBRACE)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
ICON Clinical Research
Information provided by (Responsible Party):
Stealth Peptides, Inc.
ClinicalTrials.gov Identifier:
NCT01572909
First received: March 28, 2012
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Reperfusion Injury
STEMI
Drug: Bendavia (MTP-131)
Drug: Placebo
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Stealth Peptides, Inc.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

    Defined as:

    • 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 ]

    Determined by:

    • 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.


Estimated Enrollment: 300
Study Start Date: April 2012
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Bendavia™ Drug: Bendavia (MTP-131)
0.05 mg/kg/hr
Placebo Comparator: Placebo Drug: Placebo
Identically appearing placebo

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 and <85 years
  • The patient presents with first-time acute, anterior wall STEMI scheduled to undergo primary PCI and stenting.
  • The patient has symptoms of cardiac ischemia of ≥10 minutes.
  • The patient must demonstrate an anterior wall STEMI with >0.1 mV ST-segment elevation in at least two contiguous precordial leads (i.e., V1-V4) or presumed new left bundle branch block.
  • The time from onset of symptoms of cardiac ischemia to the anticipated time of initial PCI balloon inflation does not exceed four (4) hours and it is anticipated that the door-to-balloon time will be <2 hours.
  • For female patients of child-bearing potential, an adequate form of contraception must be adhered to prior to entry into the study and for a further 3 months after the follow-up visit. Female patients of childbearing potential must have a negative serum pregnancy test prior to entry into the study.
  • Female patients not of childbearing potential (i.e. female patients who are postmenopausal since last regular menses, or have been surgically sterilized at least 1 year prior to screening visit) are eligible to enter the study.
  • For male patients with female partners of child-bearing potential, an adequate form of contraception must be adhered to prior to entry into the study and for a further 3 months after the post-study medical.
  • Written informed consent obtained that strictly adheres to the written guidelines from the local Institutional Review Board (IRB)/ Ethical Committee (EC).

Exclusion Criteria

  • Cardiogenic shock or maximal systolic blood pressure (BP) <80 mm Hg after fluid and/or vasopressor resuscitation on at least two consecutive readings.
  • Ongoing vasopressor support.
  • Uncontrolled hypertension defined as a systolic BP >180 mm Hg or a diastolic BP >110 mm Hg on at least two consecutive readings.
  • Cardiac arrest or arrhythmia requiring prolonged (>5 minutes) chest compressions/ cardiopulmonary resuscitation (CPR).
  • Prior coronary artery bypass graft surgery (CABG).
  • Prior myocardial infarction (MI).
  • Implantable cardioverter-defibrillator (ICD) or permanent pacemaker (PPM) unless known to be MRI safe. The presence of an MRI-compatible pacemaker or other MRI-compatible hardware will not be a contraindication to participation in this trial.
  • Known left ventricular ejection fraction <30% prior to the qualifying infarct.
  • History of clinically significant hepatic disturbance or chronic renal impairment at the time of admission.
  • Cerebrovascular accident (CVA) or transient ischemic attack (TIA) within the last 30 days.
  • Any known disorder that is associated with immunologic dysfunction (e.g., cancer, lymphoma, a positive serologic test for the human immunodeficiency virus, or hepatitis) more recently than 6 months before presentation or the administration of immunosuppressive drugs within 10 days of the STEMI at doses expected to be associated with immunosuppression including high dose steroids (>2.5 mg/d hydrocortisone or equal potency of synthetic steroids), TNF-α blockers or methotrexate/azathioprine.
  • Any condition that, in the Investigator's opinion, would prevent adherence to the requirements of the protocol including language barrier or current alcohol or drug abuse.
  • Contraindications (including claustrophobia) to cardiac MRI at study entry.
  • Participation in an investigational drug or device study within the 30 days prior to enrollment into the EMBRACE-STEMI Trial or anticipated within the next 4 days.
  • Female patients who are pregnant or breastfeeding during the study or intend to within 30 days of receiving study drug.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01572909

Locations
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
Germany
Universitätsmedizin Berlin, Charité Campus Benjamin Franklin
Berlin, Germany, 12203
Staedtische Kliniken Bielefeld
Bielefeld, Germany, 33604
Marienhaus Klinikum Eifel
Bitburg, Germany, 54634
Universitaetsklinikum Freiburg
Freiburg, Germany, 79095
Klinikum Herford
Herford, Germany, 32049
Robert-Bosch-Krankenhaus Kardiologie
Stuttgart, Germany, 70376
Helios Klinikum Wuppertal, Herzzentrum Elberfeld
Wuppertal, Germany, 42117
Hungary
Semmelweis Egyetem Kardiológiai Központ, Városmajor u. 68
Budapest, Hungary, 1122
Honvédkórház-Állami Egészségügyi Központ
Budapest, Hungary, 1134
Gottsegen Gyorgy Orszagos Kardiologiai Intezet
Budapest, Hungary, 1096
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
Poland
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
Wojewodzki Szpital Specjalistyczny we Wroclawiu, Oddzial Kardiologiczny, ul. H. Kamieskiego 73a
Wroclaw, Poland, 51-124
Dolnoslaski Szpital Specjalistyczny im. T. Marciniaka, Centrum Medycyny Ratunkowe
Wroclaw, Poland, 50-420
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
Sponsors and Collaborators
Stealth Peptides, Inc.
ICON Clinical Research
Investigators
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
  More Information

No publications provided by Stealth Peptides, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Stealth Peptides, Inc.
ClinicalTrials.gov Identifier: NCT01572909     History of Changes
Other Study ID Numbers: SPIRI-201
Study First Received: March 28, 2012
Last Updated: March 31, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Stealth Peptides, Inc.:
Myocardial Reperfusion
Primary PCI
Stenting for ST-segment Elevation Myocardial Infarction

Additional relevant MeSH terms:
Myocardial Infarction
Reperfusion Injury
Wounds and Injuries
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Postoperative Complications
Pathologic Processes

ClinicalTrials.gov processed this record on July 10, 2014