ETAMI-Study: Early Thienopyridine Treatment to Improve Primary Percutaneous Coronary Intervention (PCI) in Patients With Acute Myocardial Infarction

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Daiichi Sankyo Inc.
Information provided by (Responsible Party):
Stiftung Institut fuer Herzinfarktforschung
ClinicalTrials.gov Identifier:
NCT01327534
First received: March 29, 2011
Last updated: April 11, 2013
Last verified: April 2013
  Purpose

Acute myocardial infarction is generally caused by a thrombotic occlusion of coronary arteries. Primary aim of early therapy is a fast and complete reperfusion of the infarcted myocardium. This could be achieved by either thrombolytic therapy or primary Percutaneous coronary intervention (PCI).

Comparison of the different therapies in randomized trials shows an advantage of primary PCI regarding rates of recanalisation of the infarct vessel, preservation of left ventricular (LV) function, and reduction in the rate of reinfarctions. In addition, the in-hospital mortality is lower in patients undergoing primary PCI. Nevertheless, primary PCI does not always result in a successful reperfusion despite of successful restoration of blood flow in the epicardial infarct related artery.

Effective platelet inhibition is a cornerstone of therapy in patients with STEMI. In the ISIS-2 study acetylsalicylic acid (ASA) has been shown to improve short- and long-term clinical outcome in the same extent as fibrinolysis with streptokinase. Dual platelet inhibition with ASA and a thienopyridine has been repeatedly demonstrated to be more effective than ASA alone. Clopidogrel on top of ASA improved outcome in patients with acute coronary syndromes with and without PCI in the CURE study. Furthermore, a loading dose of 300 mg clopidogrel was advantageous in elective PCI in the CREDO trial and the addition of clopidogrel to ASA improved the patency rate of the infarct related artery in patients with STEMI undergoing fibrinolysis. In the BRAVE 3 study, the addition of abciximab to a background therapy of a high loading dose of 600 mg clopidogrel plus ASA did not result in an additional clinical benefit in terms of prevention of ischemic complications in primary elective PCI, suggesting a near optimal platelet inhibition with this treatment in primary PCI. The advantage of a 600 mg loading dose seems mainly related to the more rapid onset of the full antiplatelet effect within 2-4 hours as compared to 6-8 hours after 300 mg.

However, in patients with STEMI scheduled for primary PCI an earlier effective inhibition of ADP-induced platelet aggregation, preferably within 60-90 min after administration of the drug, is needed.

The new thienopyridine prasugrel has been shown to achieve a more complete and even more rapid platelet inhibition compared to clopidogrel. This might be especially important in patients with STEMI scheduled for primary PCI. In these patients activation of platelets is more pronounced compared to patients undergoing PCI for stable CAD.

In a small substudy of the TRITON-TIMI 38 trial inhibition of platelet aggregation measured with the VASP assay was more effective with prasugrel than with clopidogrel. However, this substudy was done predominantly in patients with unstable angina and NSTEMI. In addition, none of these patients were treated in the pre-hospital phase. Therefore it is necessary to determine if in patients with acute STEMI an early administration of a high loading dose of prasugrel in comparison with clopidogrel before planned primary PCI improves the inhibition of platelet aggregation, therefore facilitates this procedure and results in an improved myocardial reperfusion before and after PCI.


Condition Intervention Phase
Myocardial Infarction (STEMI) <= 12 Hours
Drug: prasugrel
Drug: Clopidogrel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: ETAMI-Study: Early Thienopyridine Treatment to Improve Primary PCI in Patients With Acute Myocardial Infarction

Resource links provided by NLM:


Further study details as provided by Stiftung Institut fuer Herzinfarktforschung:

Primary Outcome Measures:
  • platelet reactivity index (PRI) measured by VASP phosphorylation [ Time Frame: 2 hours after initiation of therapy ] [ Designated as safety issue: No ]
    The primary endpoint is the platelet reactivity index (PRI) measured by VASP phosphorylation 2 hours after the initiation of the therapy. The VASP assay was chosen because it is not influenced by the concomitant administration of GP IIb/IIIa inhibitors, which are expected to be given in 50-60% of STEMI patients.


Secondary Outcome Measures:
  • platelet reactivity index 4 hours after initiation of therapy [ Time Frame: 4 hours after initiation of therapy ] [ Designated as safety issue: No ]
  • rate of complete (> 70%) ST segment resolution 60 minutes after PCI as assessed by an ECG core laboratory which is blinded to the treatment group [ Time Frame: 60 min after PCI ] [ Designated as safety issue: No ]
  • TIMI 2/3 patency of the infarct-related artery immediately prior to PCI done by an angiography core reading centre which is blinded to treatment group [ Time Frame: 1 hour after initiation of therapy ] [ Designated as safety issue: No ]
    Time frame: expected average. In general: "immediately prior to PCI"

  • TIMI 3 patency before PCI [ Time Frame: 1 hour after initiation of therapy ] [ Designated as safety issue: No ]
    Time frame: expected average. In general: "before PCI"

  • TIMI 3 patency after PCI [ Time Frame: 2 hours after initiation of therapy ] [ Designated as safety issue: No ]
    Time frame: expected average. In general: "after PCI"

  • ST resolution immediately before angiography [ Time Frame: 1 hour after initiation of therapy ] [ Designated as safety issue: No ]
    Time frame: expected average. In general: "immediately before angiography"

  • partial or no ST resolution 60 minutes after PCI [ Time Frame: 60 minutes after PCI ] [ Designated as safety issue: No ]
  • ST segment deviation 60 minutes after PCI [ Time Frame: 60 minutes after PCI ] [ Designated as safety issue: No ]
  • death, re-MI, stent thrombosis and urgent revascularisation until 48 hours, day 7 and 30 days [ Time Frame: 48 hours, day 7, day 30 ] [ Designated as safety issue: Yes ]
  • stroke (hemorrhagic, non-hemorrhagic) [ Time Frame: day 30 ] [ Designated as safety issue: Yes ]
  • severe bleeding complications according to the TIMI and GUSTO classifications [ Time Frame: day 30 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 70
Study Start Date: May 2011
Estimated Study Completion Date: June 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: prasugrel
treatment with a 60 mg loading dose prasugrel, followed by a maintenance dose of 10 mg for 30 days
Drug: prasugrel
treatment with a 60 mg loading dose prasugrel, followed by a maintenance dose of 10 mg for 30 days
Active Comparator: clopidogrel
treatment with a 600 mg loading dose clopidogrel, followed by a maintenance dose of 75 mg for 30 days
Drug: Clopidogrel
treatment with a 600 mg loading dose clopidogrel, followed by a maintenance dose of 75 mg for 30 days

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years and < 75 years
  • Acute STEMI ≤ 12 h defined as 1. Angina or equivalent symptoms > 30 min and 2. ST elevation ≥ 2 leads (≥ 2 mm precordial leads, ≥ 1 mm limb leads) or ST depression ≥ 1 mm precordial leads in posterior MI
  • planned percutaneous coronary intervention
  • legal capacity
  • informed consent
  • first medical contact in the prehospital setting or in a non-PCI hospital (this criterion was changed by a protocol amendment in autumn 2012 to "first medical contact in the prehospital setting, in a non-PCI hospital, or in a PCI-hospital, if the expected time until the start of the scheduled PCI is at least 20 minutes")

Exclusion Criteria:

  • Age ≥ 75 years
  • Body weight < 60 kg
  • Thrombolytic therapy within 24 hours before randomization
  • Oral anticoagulation
  • Known hemorrhagic diathesis
  • History of Stroke or TIA
  • Cardiogenic shock
  • Evidence of an active gastrointestinal or urogenital bleeding
  • Major surgery within 6 weeks
  • Contraindication to prasugrel or clopidogrel
  • Severe renal or hepatic insufficiency
  • Contraindication to coronary angiography
  • Planned administration of a GP IIb/IIIa-Inhibitor before angiography
  • Pregnant or nursing (lactating) women
  • Patients currently (within the last 10 days) treated with clopidogrel, prasugrel, ticlopidine, or ticagrelor
  • Uncontrollable hypertension (blood pressure ≥ 200/110 mmHg in repeated measurements)
  • Treatment with NSAIDs
  • Participation in another clinical or device trial within the previous 30 days
  • First medical contact in a PCI-hospital (this criterion was changed by a protocol amendment in autumn 2012 to "Expected time between administration of loading dose and start of PCI is < 20 minutes")
  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: NCT01327534

Locations
France
Hospital Pitie-Salpetriere
Paris, France, 75013
Germany
Charité Campus Benjamin Franklin, Med. Klinik II
Berlin, Germany, 12203
Klinikum Ludwigshafen, Med. Klinik B
Ludwigshafen, Germany, 67063
Sponsors and Collaborators
Stiftung Institut fuer Herzinfarktforschung
Daiichi Sankyo Inc.
Investigators
Principal Investigator: Uwe Zeymer, MD Klinikum Ludwigshafen
  More Information

No publications provided

Responsible Party: Stiftung Institut fuer Herzinfarktforschung
ClinicalTrials.gov Identifier: NCT01327534     History of Changes
Other Study ID Numbers: ETAMI
Study First Received: March 29, 2011
Last Updated: April 11, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Stiftung Institut fuer Herzinfarktforschung:
STEMI
clopidogrel
prasugrel
platelet reactivity index
ST resolution

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Clopidogrel
Prasugrel
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 21, 2014