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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01572909
Recruitment Status : Completed
First Posted : April 6, 2012
Last Update Posted : December 10, 2015
Sponsor:
Collaborator:
ICON Clinical Research
Information provided by (Responsible Party):
Stealth BioTherapeutics Inc.

Tracking Information
First Submitted Date  ICMJE March 28, 2012
First Posted Date  ICMJE April 6, 2012
Last Update Posted Date December 10, 2015
Study Start Date  ICMJE April 2012
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 4, 2012)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2012)
  • 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 ]
    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. ]
    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. ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Myocardial Effects of Bendavia for Reducing Reperfusion Injury in Patients With Acute Coronary Events
Official Title  ICMJE 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
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Reperfusion Injury
  • STEMI
Intervention  ICMJE
  • Drug: Bendavia (MTP-131)
    0.05 mg/kg/hr
  • Drug: Placebo
    Identically appearing placebo
Study Arms  ICMJE
  • Active Comparator: Bendavia™
    Intervention: Drug: Bendavia (MTP-131)
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 31, 2014)
300
Original Estimated Enrollment  ICMJE
 (submitted: April 4, 2012)
200
Actual Study Completion Date  ICMJE February 2015
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Hungary,   Poland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01572909
Other Study ID Numbers  ICMJE SPIRI-201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Stealth BioTherapeutics Inc.
Study Sponsor  ICMJE Stealth BioTherapeutics Inc.
Collaborators  ICMJE ICON Clinical Research
Investigators  ICMJE
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
PRS Account Stealth BioTherapeutics Inc.
Verification Date November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP