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Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting (ALPHEUS)

This study is currently recruiting participants.
Verified July 2017 by Assistance Publique - Hôpitaux de Paris
Sponsor:
ClinicalTrials.gov Identifier:
NCT02617290
First Posted: November 30, 2015
Last Update Posted: August 1, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Action Research Group
AstraZeneca
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
  Purpose

The new P2Y12 inhibitors prasugrel (Efient®-Effient®) and ticagrelor (Brilique®-Brilinta®) have shown promising results in the respective TRITON and PLATO trials making of prasugrel and ticagrelor recommended first line treatments for acute coronary syndrome ACS (ESC Guidelines: Class 1 LOE B). These two drugs showed superiority over clopidogrel in ACS patients undergoing percutaneous coronary intervention (PCI), by the dramatic diminution of stent thrombosis, the reduction in death or Myocardial Infarction (MI) as well as the reduction in death in a meta-analysis.

The field of elective PCI (stable patients) has not been studied with these 2 new drugs and clopidogrel remains the standard of care. However, off-label use of prasugrel and ticagrelor is increasing in patients undergoing high risk elective PCI (left main, diabetics, multiple stenting, high risk of stent thrombosis, no clopidogrel pretreatment…) but is not supported by scientific evidence. More than half of PCI patients undergo elective stenting for proven ischemia and/or stable angina, a relatively safe procedure with the use of the latest generation of stents. However complications remain either frequent when considering PCI-related myonecrosis/myocardial injury that have been linked to the prognosis of patients or rare but serious when considering stent thrombosis, Q wave MI or stroke, leaving room for improvement with these two newest drugs.

The investigators propose to perform a multicenter international study in stable patients undergoing elective PCI with a randomization between clopidogrel and ticagrelor. The investigators hypothesize that this study will show superiority of the new P2Y12 inhibitor over clopidogrel in elective PCI on the primary ischemic endpoint (peri-procedural MI and myocardial injury) without significant excess bleeding (BARC definition).


Condition Intervention Phase
Coronary Artery Disease Myocardial Ischemia Myocardial Infarction Stent Thrombosis Cardiovascular Diseases Drug: Ticagrelor Drug: Clopidogrel Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting: The ALPHEUS Study

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Ischemic Episode [ Time Frame: 48 hours (hospital discharge if earlier) ]
    The rate of PCI-related myocardial infarction (MI type 4) or injury (I) within 48 hours (or at hospital discharge if earlier) of elective PCI/stent


Secondary Outcome Measures:
  • Bleeding Episode [ Time Frame: 48 hours (or discharge if it occurs earlier) ]
    The rate of major bleeding events as assessed by the BARC criteria (BARC type 3 or 5) at 48 hours (or discharge if it occurs earlier)


Estimated Enrollment: 1900
Actual Study Start Date: January 9, 2017
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ticagrelor Arm
Ticagrelor is an oral antiplatelet agent which was approved for use in the European Union by the European Commission on December 3, 2010. The drug was approved by the US Food and Drug Administration on July 20, 2011. It is available as round, yellow tablets (90 mg). The standard dose is 90 mg twice a day during the maintenance phase and 180 mg once for the loading dose. It is approved for duration of 12 month in ACS patients and will be used for duration of one month in the ALPHEUS Study.
Drug: Ticagrelor
Ticagrelor Loading dose of 180mg given after angiography and before PCI , followed by a 30 days treatment with the maintenance dose of 90mg bid.
Other Name: Brilique, Brilinta
Active Comparator: Clopidogrel Arm
Clopidoprel is an oral antiplatelet agent which was approved for use in the European Union by the European Commission in 1997 and available as generic since 2007. The standard dose of clopidogrel is one 75 mg tablet once a day. The dosage for the loading dose is normally 300 mg but 600 mg is also used. Clopidogrel is the standard of care for PCI at the moment.
Drug: Clopidogrel
Clopidogrel Loading dose of 300 or 600mg given after angiography and before PCI , followed by a 30 days treatment with the maintenance dose of 75mg per day.
Other Name: Plavix

  Eligibility

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female ≥18 years of age
  • Having at least one high-risk feature (Age > 75, Renal insufficiency (Clearance below 60ml/min calculated with Cockcroft-Gault formula), Diabetes Mellitus, Overweight (BMI >30), History of ACS (in the past 12 months) including UA/NSTEMI and STEMI, LVEF < 40% and/or prior episode of heart failure, Multivessel disease (2 or 3 V), Multiple stents needed defined as i) more than one stent implanted in one vessel or ii) more than 2 stents in 2 or more vessels, or iii) total stent length envisioned > 30mm, Left main stenting, Bifurcation stenting (whatever the technique), ACC/AHA type B2 or C lesion , Stenting of venous or arterial coronary graft).
  • Undergoing non-emergent single or multiple sites/vessels PCI during the same procedure)
  • Negative troponin before enrolment (according to local measurement - hsTn preferably)
  • Informed consent obtained in writing at enrolment into the study

Exclusion Criteria:

  • Women of child-bearing potential (ie, those who are not chemically or surgically sterilised or who are not post-menopause) who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator OR women who have a positive pregnancy test at randomisation OR women who are breast-feeding
  • Thrombolytic therapy within the previous 24 hours
  • Undergoing primary PCI for ongoing STEMI
  • Undergoing rescue PCI after failed thrombolysis
  • Any other elective PCI scheduled within the following 30 days after the index PCI
  • History of intracranial haemorrhage at any time
  • Increased bleeding risk: intracranial tumor or aneurysm; recent trauma or major surgery (< 1 month) (including bypass surgery), active gastrointestinal, active bleeding
  • Uncontrolled arterial hypertension (defined as a systolic BP ≥180 mmHg and/or diastolic BP ≥100 mmHg)
  • Recent (<48 hours) or planned spinal/epidural anesthesia or puncture
  • Impaired haemostasis such as known International Normalized Ratio (INR) >1.5; past or present bleeding disorder (including congenital bleeding disorders such as von Willebrand's disease or hemophilia, acquired bleeding disorders, and unexplained clinically significant bleeding disorders), thrombocytopenia (platelet count <100,000/μL)
  • Known severe and moderated hepatic impairment
  • Treatment with oral anticoagulant therapy within 72 hours prior to inclusion or current need for oral anticoagulant therapy in the next month.
  • Use of abciximab within the previous 7 days or, tirofiban or eptifibatide within the past 12 hours of index PCI
  • Prohibited treatments (see section 8.3)
  • Inability to give informed consent or high likelihood of being unavailable for follow-up
  • Participation in another clinical research protocol with other investigational agents or devices within the previous 30 days, planned use of investigational drugs or devices, or previous enrolment in this trial (routine care authorized)
  • Known intolerance to clopidogrel or ticagrelor
  • Hypersensitivity to ticagrelor or its excipients
  • Hypersensitivity to clopidogrel or its excipients
  • Patient on prasugrel or ticagrelor before the procedure
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02617290


Contacts
Contact: Johanne SILVAIN, MD-PhD +33 1 42 16 30 07 johanne.silvain@aphp.fr
Contact: Gilles MONTALESCOT, MD-PhD +33 1 42 16 30 07 gilles.montalescot@aphp.fr

Locations
France
Institut de Cardiologie - USIC - Hôpital Pitié-Salpêtrière Recruiting
Paris, France, 75013
Contact: Johanne SILVAIN, MD    33 1 42 16 30 01    johanne.silvain@aphp.fr   
Contact: Gilles MONTALESCOT, MD, PhD    33 1 42 16 30 07    gilles.montalescot@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Action Research Group
AstraZeneca
Investigators
Principal Investigator: Johanne SILVAIN, MD-PhD Assistance Publique - Hôpitaux de Paris
  More Information

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02617290     History of Changes
Other Study ID Numbers: P141103
First Submitted: September 15, 2015
First Posted: November 30, 2015
Last Update Posted: August 1, 2017
Last Verified: July 2017

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Coronary Artery Disease (CAD)
Percutaneous Coronary Intervention (PCI)

Additional relevant MeSH terms:
Infarction
Cardiovascular Diseases
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Myocardial Infarction
Ischemia
Thrombosis
Pathologic Processes
Necrosis
Heart Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Embolism and Thrombosis
Clopidogrel
Ticlopidine
Ticagrelor
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 Enzyme Inhibitors