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

NCT ID: NCT01572909

Last Updated: 2020-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2015-02-28

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).

Detailed Description

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 on a background of standard-of-care therapy for reduction of reperfusion injury in patients with first time acute, anterior wall STEMI.

Patients were randomized to receive either an infusion of elamipretide at 0.05 mg/kg/hr or an identically appearing placebo administered as an IV infusion at 60 mL/hr. The infusion began at least 15 minutes but no more than 1 hour prior to the anticipated reperfusion event and continued through approximately 1 hour following re-establishment of blood flow through the culprit vessel.

The reduction of reperfusion injury, or infarct size, was estimated using the area under the curve (AUC) of the serum creatine kinase (CK) isoenzyme, as well as using magnetic resonance imaging (MRI) performed on the Day 4±1 and on Day 30±7 (both MRI assessments measured infarct size and the ratio of infarct size to myocardial mass). The analyses of cardiac MRI data were performed for both the primary endpoint population and also in all patients who had adequate Day 4/Day 30 cardiac MRI studies.

After completion of the percutaneous coronary intervention (PCI) and stenting, patients received standard medical treatment.

Conditions

Reperfusion Injury; STEMI

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Bendavia™

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.

Group Type: ACTIVE_COMPARATOR

Bendavia (MTP-131)

Intervention Type: DRUG

0.05 mg/kg/hr

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Identically appearing placebo

Interventions

Bendavia (MTP-131)

0.05 mg/kg/hr

Intervention Type: DRUG

Placebo

Identically appearing placebo

Intervention Type: DRUG

Other Intervention Names

MTP-131; Elamipretide

Eligibility 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 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).

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), 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ICON Clinical Research

INDUSTRY

Sponsor Role: collaborator

Stealth BioTherapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anjan Chakrabarti, MD

Role: PRINCIPAL_INVESTIGATOR

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

C. M. Gibson, MD

Role: STUDY_CHAIR

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

Locations

Staedtische Kliniken Bielefeld

Bielefeld, , Germany

Marienhaus Klinikum Eifel

Bitburg, , Germany

Advanced Medical Research Center

Port Orange, Florida, United States

Henry Ford Hospital

Detroit, Michigan, United States

Creighton Cardiac Center

Omaha, Nebraska, United States

Universitätsmedizin Berlin, Charité Campus Benjamin Franklin

Berlin, , Germany

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Klinikum Herford

Herford, , Germany

Robert-Bosch-Krankenhaus Kardiologie

Stuttgart, , Germany

Helios Klinikum Wuppertal, Herzzentrum Elberfeld

Wuppertal, , Germany

Gottsegen Gyorgy Orszagos Kardiologiai Intezet

Budapest, , Hungary

Semmelweis Egyetem Kardiológiai Központ, Városmajor u. 68

Budapest, , Hungary

Honvédkórház-Állami Egészségügyi Központ

Budapest, , Hungary

PTE Klinikai Központ Szívgyógyászati Klinika

Pécs, , Hungary

Szent György Kórház, II. Belgyógyászati Osztály

Székesfehérvár, , Hungary

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

Zalaegerszeg, , Hungary

Medical University of Bialystok

Bialystok, , Poland

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

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

Katowice, , Poland

Wojewodzki Szpital Zespolony w Kielcach, Swietokrzyskie Centrum Kardiologii

Kielce, , Poland

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

Krakow, , Poland

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

Lodz, , Poland

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

Opole, , Poland

Centrum Kardiologii Inwazyjnej, Elektroterapii i Angiologii

Oświęcim, , Poland

Szpital Bielanski im. ks. Jerzego Popieluszki

Warsaw, , Poland

Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, Pracownia Kardiologii Inwazyjnej

Warsaw, , Poland

Instytut Kardiologii im. Prymasa Tysiaclecia Stefana Kardynala Wyszynskiego

Warsaw, , Poland

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

Wroclaw, , Poland

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

Wroclaw, , Poland

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, , Poland

Countries

United States; Germany; Hungary; Poland

References

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.

Reference Type: DERIVED

PMID: 27392509 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23537966 (View on PubMed)

Other Identifiers

SPIRI-201

Identifier Type: -

Identifier Source: org_study_id