Evaluation of Myocardial Effects of MTP-131 for Reducing Reperfusion Injury in Patients With Acute Coronary Events

NCT01572909 | Completed Phase 2 Results DMC

• 1 other identifier: SPIRI-201
• Study Type: interventional
• Target: 300
• Locations: 4 countries
• Sites: 30

Brief Summary

The EMBRACE-STEMI trial was a Phase 2a prospective, multicenter, multinational randomized, double-blind, placebo-controlled study designed to assess the safety, tolerability, and efficacy of IV administered elamipretide (also known as MTP-131, or Bendavia) on a background of standard-of-care therapy for reduction of reperfusion injury in patients with first time acute, anterior wall ST-segment elevation myocardial infarction (STEMI).

Conditions

Reperfusion Injury; STEMI

Keywords

Myocardial Reperfusion; Primary PCI; Stenting for ST-segment Elevation Myocardial Infarction

Outcome Measures

Primary Outcomes (1)

• Area Under the Curve (AUC) of Serum Creatine Kinase Isoenzyme Type Muscle-brain (CK-MB)

  Infarct size as measured by the AUC of serum CK-MB at 24 and 72 hours post-PCI

  The initial 24 and 72 hours post-percutaneous coronary intervention (PCI)

Secondary Outcomes (19)

• AUC of Troponin 1 Enzyme

  Initial 24 and 72 hours post-PCI

• Ratio of Volume of Infarcted Myocardium to Left Ventricular Mass

  Day 30 + 7

• Thrombosis in Myocardial Infarction (TIMI) Perfusion Grade Flow at Completion of PCI

  Initiation to Completion of PCI, no longer than 4 hours

• Corrected TIMI Frame Count

  Completion of PCI, no longer than 4 hours

• ST-Segmented Elevation From Pre-PCI to 24 Hours Post-PCI and Presence of ST-Segmented Resolution

  pre-PCI to 24 hours post-PCI

Study Arms (2)

Bendavia™

ACTIVE COMPARATOR

Bendavia™ administered intravenously at 0.05 mg/kg/hr at least 15, but no more than 60 minutes, prior to the anticipated time of the PCI, and continued for 1 hour after re-establishment of blood flow through the culprit vessel.

Drug: Bendavia (MTP-131)

Placebo

PLACEBO COMPARATOR

Placebo administered intravenously at 60 mL/hr at least 15, but no more than 60 minutes, prior to the anticipated time of the PCI, and continued for 1 hour after re-establishment of blood flow through the culprit vessel.

Drug: Placebo

Interventions

Bendavia (MTP-131) DRUG

0.05 mg/kg/hr

Also known as: MTP-131, Elamipretide

Bendavia™

Placebo DRUG

Identically appearing placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 millivolt (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).

You may not qualify if:

• 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), tumor necrosis factor-alpha (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.

Sponsors & Collaborators

• Stealth BioTherapeutics Inc.: lead
• ICON Clinical Research: collaborator

Study Sites (30)

Advanced Medical Research Center

Port Orange, Florida, 32127, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Creighton Cardiac Center

Omaha, Nebraska, 68131, United States

Location

Universitätsmedizin Berlin, Charité Campus Benjamin Franklin

Berlin, 12203, Germany

Location

Staedtische Kliniken Bielefeld

Bielefeld, 33604, Germany

Location

Marienhaus Klinikum Eifel

Bitburg, 54634, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, 79095, Germany

Location

Klinikum Herford

Herford, 32049, Germany

Location

Robert-Bosch-Krankenhaus Kardiologie

Stuttgart, 70376, Germany

Location

Helios Klinikum Wuppertal, Herzzentrum Elberfeld

Wuppertal, 42117, Germany

Location

Gottsegen Gyorgy Orszagos Kardiologiai Intezet

Budapest, 1096, Hungary

Location

Semmelweis Egyetem Kardiológiai Központ, Városmajor u. 68

Budapest, 1122, Hungary

Location

Honvédkórház-Állami Egészségügyi Központ

Budapest, 1134, Hungary

Location

PTE Klinikai Központ Szívgyógyászati Klinika

Pécs, H-7624, Hungary

Location

Szent György Kórház, II. Belgyógyászati Osztály

Székesfehérvár, H-8000, Hungary

Location

Zala Megyei Kórház, Kardiológiai Osztály, Zrínyi Miklós út 1.

Zalaegerszeg, H-8900, Hungary

Location

Medical University of Bialystok

Bialystok, 15-276, Poland

Location

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, 40-635, Poland

Location

SPSK Nr 7 Slaskiego Uniwersytetu Medycznego w Katowicach, Gornoslaskie Centrum Medyczne im. Prof. Leszaka Gieca, I Oddzial Kardiologii, ul. Ziolowa 45-47

Katowice, 40-635, Poland

Location

Wojewodzki Szpital Zespolony w Kielcach, Swietokrzyskie Centrum Kardiologii

Kielce, 25-736, Poland

Location

Krakowski Szpital Specjalistyczny im. Jana Pwla II, Centrum Interwencyjnego Leczenia Chorob Serca i Naczyn z Pododdzialem Kariologii Interwencyjnej

Krakow, 31-202, Poland

Location

Wojewodzki Specjalistyczny Szpital im WI. Bieganskiego, II Katedra i Klinika Kardiologii Uniwersytetu Medycznego w Lodzi, Pracownia Kardiologii Inwazyinej, ul. Kniaziewicza 1/5

Lodz, 91-347, Poland

Location

SP ZOZ Wojewodzkie Centrum Medyczne, Zaklad Diagnostyki Obrazowej, AI. W. Witosa 26

Opole, 45-418, Poland

Location

Centrum Kardiologii Inwazyjnej, Elektroterapii i Angiologii

Oświęcim, 32-600, Poland

Location

Szpital Bielanski im. ks. Jerzego Popieluszki

Warsaw, 01-809, Poland

Location

Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, Pracownia Kardiologii Inwazyjnej

Warsaw, 02-097, Poland

Location

Instytut Kardiologii im. Prymasa Tysiaclecia Stefana Kardynala Wyszynskiego

Warsaw, 04-628, Poland

Location

Dolnoslaski Szpital Specjalistyczny im. T. Marciniaka, Centrum Medycyny Ratunkowe

Wroclaw, 50-420, Poland

Location

Wojewodzki Szpital Specjalistyczny we Wroclawiu, Oddzial Kardiologiczny, ul. H. Kamieskiego 73a

Wroclaw, 51-124, Poland

Location

Samodzielny Publiczny Szpital Wojewodzki im. Papieza Jana Pawla II w Zamosciu, Oddzial Kardiologii z Pododdzialem Intensywnej Terapil Kardiologicznej, ul. Aleje Jana Pawta II 10

Zamość, 22-400, Poland

Location

Related Publications (2)

• Daaboul Y, Korjian S, Weaver WD, Kloner RA, Giugliano RP, Carr J, Neal BJ, Chi G, Cochet M, Goodell L, Michalak N, Rusowicz-Orazem L, Alkathery T, Allaham H, Routray S, Szlosek D, Jain P, Gibson CM. Relation of Left Ventricular Mass and Infarct Size in Anterior Wall ST-Segment Elevation Acute Myocardial Infarction (from the EMBRACE STEMI Clinical Trial). Am J Cardiol. 2016 Sep 1;118(5):625-31. doi: 10.1016/j.amjcard.2016.06.025. Epub 2016 Jun 15.

  PMID: 27392509 DERIVED

• Chakrabarti AK, Feeney K, Abueg C, Brown DA, Czyz E, Tendera M, Janosi A, Giugliano RP, Kloner RA, Weaver WD, Bode C, Godlewski J, Merkely B, Gibson CM. Rationale and design of the EMBRACE STEMI study: a phase 2a, randomized, double-blind, placebo-controlled trial to evaluate the safety, tolerability and efficacy of intravenous Bendavia on reperfusion injury in patients treated with standard therapy including primary percutaneous coronary intervention and stenting for ST-segment elevation myocardial infarction. Am Heart J. 2013 Apr;165(4):509-514.e7. doi: 10.1016/j.ahj.2012.12.008. Epub 2013 Feb 15.

  PMID: 23537966 DERIVED

MeSH Terms

Conditions

Reperfusion Injury; ST Elevation Myocardial Infarction

Interventions

arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Infarction; Ischemia; Necrosis

Results Point of Contact

• Title: Jim Carr, Pharm.D. Chief Clinical Development Officer
• Organization: Stealth BioTherapeutics, Inc

jim.carr@stealthbt.com

1-617-600-6888

Study Officials

• Anjan Chakrabarti, MD

  Beth Israel Deaconess Medical Center, Interventional Cardiology, 185 Pilgrim Rd, Baker 4, Boston, MA 02215

  PRINCIPAL INVESTIGATOR

• C. M. Gibson, MD

  Beth Israel Deaconess Medical Center, Interventional Cardiology, 185 Pilgrim Rd, Baer 4, Boston, MA 02215

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2012
• First Posted: April 6, 2012
• Study Start: April 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: February 1, 2015
• Last Updated: June 11, 2020
• Results First Posted: June 11, 2020

Record last verified: 2020-05

Locations

HU (6); PL (14); DE (7); US (3)