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Reperfusion InjuryPhase 2EMBRACENCT01572909

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

A Phase 2 study testing Bendavia (MTP-131) in people with Reperfusion Injury and STEMI, run by Stealth BioTherapeutics Inc. at 30 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Reperfusion Injury, STEMI
What is being tested?
Bendavia (MTP-131)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
300 participants
Where
30 sitesin 4 countries
Study dates
Apr 2012to Feb 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

30 sites in 4 countries.

30 sites in 4 countries

Poland14 sites

  • Medical University of Bialystok

    Bialystok, 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, 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, 40-635

  • Wojewodzki Szpital Zespolony w Kielcach, Swietokrzyskie Centrum Kardiologii

    Kielce, 25-736

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

    Krakow, 31-202

  • 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

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

    Opole, 45-418

  • Centrum Kardiologii Inwazyjnej, Elektroterapii i Angiologii

    Oświęcim, 32-600

  • Szpital Bielanski im. ks. Jerzego Popieluszki

    Warsaw, 01-809

  • Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie, Pracownia Kardiologii Inwazyjnej

    Warsaw, 02-097

  • Instytut Kardiologii im. Prymasa Tysiaclecia Stefana Kardynala Wyszynskiego

    Warsaw, 04-628

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

    Wroclaw, 50-420

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

    Wroclaw, 51-124

  • 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

Other trials in Poland

Germany7 sites

  • Universitätsmedizin Berlin, Charité Campus Benjamin Franklin

    Berlin, 12203

  • Staedtische Kliniken Bielefeld

    Bielefeld, 33604

  • Marienhaus Klinikum Eifel

    Bitburg, 54634

  • Universitaetsklinikum Freiburg

    Freiburg im Breisgau, 79095

  • Klinikum Herford

    Herford, 32049

  • Robert-Bosch-Krankenhaus Kardiologie

    Stuttgart, 70376

  • Helios Klinikum Wuppertal, Herzzentrum Elberfeld

    Wuppertal, 42117

Other trials in Germany

Hungary6 sites

  • Gottsegen Gyorgy Orszagos Kardiologiai Intezet

    Budapest, 1096

  • Semmelweis Egyetem Kardiológiai Központ, Városmajor u. 68

    Budapest, 1122

  • Honvédkórház-Állami Egészségügyi Központ

    Budapest, 1134

  • PTE Klinikai Központ Szívgyógyászati Klinika

    Pécs, H-7624

  • Szent György Kórház, II. Belgyógyászati Osztály

    Székesfehérvár, H-8000

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

    Zalaegerszeg, H-8900

Other trials in Hungary

United States3 sites

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Creighton Cardiac Center

    Omaha, Nebraska, 68131

  • Advanced Medical Research Center

    Port Orange, Florida, 32127

Other trials in United States

About this study

Official title: A Phase 2a Trial to Evaluate the Safety, Tolerability and Efficacy of Intravenous MTP-131 on Reperfusion Injury in Patients Undergoing Primary Percutaneous Coronary Intervention and Stenting for ST-segment Elevation Myocardial Infarction Infarction

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).

Read the 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.

Being tested
Bendavia (MTP-131), Placebo
Keywords
Myocardial Reperfusion, Primary PCI, Stenting for ST-segment Elevation Myocardial Infarction
Medical subject headings
Reperfusion Injury, ST Elevation Myocardial Infarction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bendavia (MTP-131)Drug

    Also called MTP-131, Elamipretide

    0.05 mg/kg/hr

  • PlaceboDrug

    Identically appearing placebo

Study groups in NCT01572909
Study groupRoleWhat they receive
Bendavia™Active comparatorBendavia™ 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.
Receives: Drug: Bendavia (MTP-131)
PlaceboPlacebo comparatorPlacebo 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

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

Secondary outcomes (19)

  1. AUC of Troponin 1 Enzyme

    Infarct size as calculated by the AUC of Troponin I Enzyme over the initial 24 and 72 hours post-PCI

    Measured: Initial 24 and 72 hours post-PCI

  2. Ratio of Volume of Infarcted Myocardium to Left Ventricular Mass

    Cardiac infarct size calculated as the ratio of volume of infarcted myocardium to left ventricular mass at Day 30 as measured by MRI.

    Measured: Day 30 + 7

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

    TIMI perfusion grade flow at completion of PCI will be categorized as 0,1, or 1.5, 2 or 2.5, 3, and treated as ordinal data, where higher score means better perfusion and lower score means worse perfusion and worse outcome.

    Measured: Initiation to Completion of PCI, no longer than 4 hours

  4. Corrected TIMI Frame Count

    Corrected TIMI Frame Count at Completion of PCI as captured by angiogram and analyzed as a continuous variable.

    Measured: Completion of PCI, no longer than 4 hours

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

    ST-Segmented Elevation from pre-PCI to 24 hours post-PCI and Presence of ST-Segmented Resolution by ECG

    Measured: pre-PCI to 24 hours post-PCI

  6. Change in Serum Creatinine From Baseline

    Change in serum creatinine, from baseline (prior to study drug administration) to Day 30 +7 post-PCI

    Measured: Day 30 +7

  7. Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline

    Change in eGFR from baseline (prior to study drug administration) to Day 30 +7 post-PCI

    Measured: Day 30 +/- 7

  8. Cystatin C Change From Baseline

    Change in Cystatin C from baseline (prior to study drug administration) to Day 30 +7 post-PCI

    Measured: Day 30 + 7

  9. Blood Urea Nitrogen (BUN) Change From Baseline

    Blood Urea Nitrogen (BUN) Change from baseline (prior to study drug administration) to Day 30 + 7 post-PCI

    Measured: Baseline to Day 30

  10. Number and Percent of Grade 1 Episode of Contrast-Induced Nephropathy Post-PCI

    Number of Participants with Grade 1 Episode of Contrast-Induced Nephropathy within 48 hours of initial PCI or MRI, based on lab data.

    Measured: Baseline to 48 hours post PCI or MRI

  11. Immediate Myocardial Complications: Ventricular Tachycardia or Fibrillation

    Number and percent of participants with Immediate Myocardial Complications: Ventricular Tachycardia or Fibrillation Requiring Medical Intervention

    Measured: Baseline up to 1 hour post-PCI

  12. Immediate Myocardial Complications: Mechanical Complications

    Number and Percent of Participants with Immediate Myocardial Complications: Mechanical Complications: (Free wall Rupture, Ventricular Septal Defect, Ischemic Mitral Regurgitation)

    Measured: Baseline up to 1 hour post-PCI

  13. Emergency Use of Medications During PCI Procedure

    Emergency Use of Nitroprusside, Calcium Channel Blocker, Adenosine Administration During the PCI Procedure

    Measured: Initiation to Completion of PCI, no longer than 4 hours

  14. ProB-type Natriuretic Peptide (NT-proBNP) Change From Baseline to Day 30

    NT-proBNP: Change from baseline to Day 30 +7 (Laboratory marker for chronic heart failure (CHF) and systemic inflammation.)

    Measured: Baseline to Day 30

  15. High Sensitivity C-Reactive Protein (hsCRP): Change From Baseline to Day 30

    High Sensitivity C-Reactive Protein (hsCRP): Change from baseline to Day 30 +7 (Laboratory Marker for CHF and Systemic Inflammation)

    Measured: Baseline to Day 30

  16. Left Ventricular (LV) Ejection Fraction (%)

    Difference in Left Ventricular (LV) Ejection Fraction (%) from Day 4 To Day 30

    Measured: Day 4 to Day 30

  17. Difference Between Left Ventricular End Diastolic Volume, Corrected

    Difference between Left Ventricular End Diastolic Volume Corrected for Body Surface Area between Day 4 and Day 30

    Measured: Day 4 and Day 30

  18. Difference Between Left Ventricular End Systolic Volume, Corrected

    Difference between Left Ventricular End Systolic Volume Corrected for Body Surface Area from Day 4 and Day 30

    Measured: Day 4 and Day 30

  19. Chronic Heart Failure

    Number and Percentage of Patients with Clinical Events: Chronic Heart Failure beginning within 24 hours after PCI but within the duration of the index hospitalization (Subjects with CHF started within 24 hours after the last balloon deflation while the patient was still in the hospital {including patients who had missing discharge date}).

    Measured: Within 24 hours after PCI

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Apr 2012 (estimated)
  2. Study startApr 2012
  3. Primary completionNov 2014
  4. Study completionFeb 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
300 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01572909
Sponsor's protocol ID
SPIRI-201
Acronym
EMBRACE
Status last verified
May 2020
First submitted
28 Mar 2012
Last updated
11 Jun 2020
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 27392509

  • 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.

    PubMed 23537966

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bendavia (MTP-131) in people with Reperfusion Injury and STEMI, run by Stealth BioTherapeutics Inc. at 30 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in Poland, Germany, Hungary, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Curve (AUC) of Serum Creatine Kinase Isoenzyme Type Muscle-brain (CK-MB) (time frame: The initial 24 and 72 hours post-percutaneous coronary intervention (PCI)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01572909, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2020.

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