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Randomized Comparison of Cangrelor, Tirofiban and Prasugrel in Patients With STEMI Referred for Primary PCI. (FABOLUS-FASTER)

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ClinicalTrials.gov Identifier: NCT02978040
Recruitment Status : Recruiting
First Posted : November 30, 2016
Last Update Posted : October 24, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

Brief Summary:

Primary percutaneous coronary intervention (PCI) is the main reperfusion therapy in patients with ST-elevation myocardial infarction (STEMI). The optimal platelet inhibition at the time of PCI is fundamental, however, the comparative speed of action of cangrelor as opposed to tirofiban and to chewed or integer loading dose of prasugrel is unknown.

The purpose of this trial is to assess the inhibition of platelet aggregation with different regimens on platelet inhibition (tirofiban bolus+infusion, cangrelor bolus+infusion, prasugrel chewed loading dose, prasugrel integer loading dose) in the early phase of primary PCI.


Condition or disease Intervention/treatment Phase
Coronary Artery Disease STEMI - ST Elevation Myocardial Infarction Drug: Cangrelor Drug: Tirofiban Drug: Prasugrel Phase 4

Detailed Description:
Primary percutaneous coronary intervention (PCI) is the main reperfusion therapy in patients with ST-elevation myocardial infarction (STEMI). Ancillary pharmacological therapy includes dual antiplatelet therapy with aspirin and an inhibitor of P2Y12 receptor, responsible of adenosine diphosphate(ADP)-mediated platelet activation.Prasugrel and ticagrelor are the most recent and efficient oral P2Y12 inhibitors available to date. However, in STEMI even prasugrel and ticagrelor could have a significant delay of onset of action. Early in-ambulance administration can increase the inhibition of P2Y12 receptor, however, the benefits versus risks balance remain uncertain. Recently, small-scale independent studies suggested that chewed or crushed loading dose of ticagrelor or prasugrel can achieve more pronounced platelet inhibition compared with standard whole tablets soon after drug administration. Yet, the delay in platelet inhibition remains considerable even after chewed or crushed loading dose of newer oral P2Y12 inhibitors and suboptimal modulation of platelet reactivity at the time of primary intervention may persist. Tirofiban and cangrelor are intravenous drugs with a more rapid onset and offset of action compared with oral agents. Both agents have been extensively tested in clinical trials including patients with STEMI. However, the comparative speed of action of cangrelor as opposed to tirofiban and to chewed or integer loading dose of prasugrel is unknown. The proposed investigation will have a prospective, randomized, design in which STEMI patients undergoing primary PCI will be randomized to receive Cangrelor or Tirofiban or Prasugrel (these patients will be further randomized to receive chewed or integer tablets). Pharmacodynamic testing will be performed at several time points to test the investigators' study hypotheses: 1) Cangrelor will have similar inhibitory effect to Tirofiban (non-inferiority of Cangrelor compared with Tirofiban); 2) Compared with Prasugrel, Cangrelor and Tirofiban will achieve more prompt and enhanced platelet inhibitory effects (superiority of both Tirofiban and Cangrelor to integer Prasugrel); 3) Compared with integer loading dose of Prasugrel, chewed Prasugrel regimen will achieve more prompt and enhanced platelet inhibitory effects (superiority of chewed Prasugrel to integer Prasugrel). This study will provide insights on the pharmacodynamic effects of these drugs and will help clinicians choose the most appropriate treatment to avoid complications related to inadequate platelet inhibition in the early phase of patients with STEMI undergoing primary PCI.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description: The study is open label. Participant and Investigators will be not masked to randomly assigned treatments. An independent blinded committee will assess clinical adverse events.
Primary Purpose: Treatment
Official Title: Facilitation Through Aggrastat or Cangrelor Bolus and Infusion Over prasugreL: a mUlticenter Randomized Open-label Trial in patientS With ST-elevation Myocardial inFarction Referred for primAry percutaneouS inTERvention.FABOLUS FASTER Trial
Actual Study Start Date : July 4, 2017
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : April 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack

Arm Intervention/treatment
Experimental: Cangrelor
Cangrelor bolus of 30 µg/Kg followed by infusion at 4 µg/Kg/min for 2 h (or to the end of PCI).
Drug: Cangrelor
Cangrelor will be administered as bolus of 30 µg/Kg followed by infusion at 4 µg/Kg/min for 2 h (or to the end of PCI); at the end of infusion, oral prasugrel at loading dose of 60 mg will be administrated, then 10 mg daily (5 mg daily if body weight < 60 kg or age > 75 years old).
Other Names:
  • Kengreal
  • Kengrexal

Active Comparator: Tirofiban
Tirofiban bolus of 25 µg/Kg bolus followed by infusion at 0.15 µg/Kg/min for 2 h (or to the end of PCI) (infusion rate of 0.075 µg/Kg/min for patients with creatinine clearance < 60 ml/min).
Drug: Tirofiban
Tirofiban will be administrated as 25 µg/Kg bolus followed by infusion at 0.15 µg/Kg/min for 2 h (or to the end of PCI) (infusion rate of 0.075 µg/Kg/min for patients with creatinine clearance < 60 ml/min); at the end of infusion, oral prasugrel at loading dose of 60 mg will be administrated, then 10 mg daily (5 mg daily if body weight < 60 kg or age > 75 years old) .
Other Name: Aggrastat

Active Comparator: Prasugrel
Prasugrel oral integer or chewed at an identical loading dose of 60 mg
Drug: Prasugrel
In the prasugrel arm no intravenous anti-platelet drug will be administered. Patients will be randomized to oral integer prasugrel or chewed oral prasugrel at an identical loading dose of 60 mg, then 10 mg daily (5 mg daily if body weight < 60 kg or age > 75 years old).
Other Name: Efient




Primary Outcome Measures :
  1. Inhibition of platelet activity (IPA, %) with LTA-ADP 20 µmol/l [ Time Frame: 30 minutes ]
    Primary outcome is platelet inhibition assessed with light transmission aggregometry (LTA) in platelet rich plasma with the addition of adenosine diphosphate (ADP) 20 µmol/l at 30 minutes from drug administration


Secondary Outcome Measures :
  1. Inhibition of platelet activity (IPA, %) with LTA-ADP 20 µmol/l [ Time Frame: 15 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours ]
    Platelet inhibition assessed with light transmission aggregometry (LTA) in platelet rich plasma with the addition of ADP 20 µmol/l at 15 minutes, 1h, 2h, 3h and 4-6h from drug administration

  2. Inhibition of platelet activity (IPA, %) with LTA-ADP 5 µmol/l [ Time Frame: 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours ]
    Platelet inhibition assessed with light transmission aggregometry (LTA) in platelet rich plasma with the addition of ADP 5 µmol/l at 15 minutes, 30 minutes, 1h, 2h, 3h and 4-6h from drug administration

  3. Inhibition of platelet activity (IPA, %) with LTA-TRAP 5 µmol/l [ Time Frame: 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours ]
    Platelet inhibition assessed with light transmission aggregometry (LTA) in platelet rich plasma with the addition of thrombin receptor-activating peptides (TRAP) 5 µmol/l at 15 minutes, 30 minutes, 1h, 2h, 3h and 4-6h from drug administration

  4. Inhibition of platelet activity (IPA, %) with LTA-TRAP 15 µmol/l [ Time Frame: 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours ]
    Platelet inhibition assessed with light transmission aggregometry (LTA) in platelet rich plasma with the addition of TRAP 15 µmol/l at 15 minutes, 30 minutes, 1h, 2h, 3h and 4-6h from drug administration

  5. Area under the curve (AUC) at Multiplate with ADP test [ Time Frame: 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours ]
    Platelet inhibition assessed with Multiplate ADP test at 15 minutes, 30 minutes, 1h, 2h, 3h and 4-6h from drug administration

  6. Area under the curve (AUC) at Multiplate with TRAP test [ Time Frame: 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours ]
    Platelet inhibition assessed with Multiplate TRAP test at 15 minutes, 30 minutes, 1h, 2h, 3h and 4-6h from drug administration

  7. Angiographic result [ Time Frame: immediately after PCI procedure ]
    Final angiographic result evaluated by proportion of patients with TIMI flow<3

  8. Electrocardiographic result [ Time Frame: immediately after PCI procedure and 90 minutes after PCI ]
    ST resolution at ECG recorded after PCI

  9. Infarct size at Cardiac Magnetic Resonance Imaging (MRI) [ Time Frame: 3 days and 4-6 months after PCI ]
    Infarct size assessed at cardiac MRI

  10. Intramyocardial haemorrhage at Cardiac Magnetic Resonance Imaging (MRI) [ Time Frame: 3 days and 4-6 months after PCI ]
    Intramyocardial haemorrhage assessed at cardiac MRI

  11. Major adverse ischemic clinical events [ Time Frame: 48 h and 30 days after PCI ]
    Major adverse ischemic clinical events (including death, cardiac death, myocardial infarction, stroke, urgent target vessel revascularization, definite/probable stent thrombosis and their combinations in composite endpoints) will be evaluated 48 hours and 30 days from primary PCI.

  12. Bleeding events [ Time Frame: 48 h and 30 days after PCI ]
    Bleeding events according to Bleeding Academic Research Consortium (BARC), Thrombolysis in Myocardial Infarction (TIMI), Global Use of Strategies To Open occluded arteries (GUSTO) bleeding scales as well as Net adverse clinical events (NACE; defined as the composite of death, non-fatal myocardial infarction, definite/probable stent thrombosis, non-fatal stroke, and BARC 2, 3, or 5 bleeding) will be evaluated at 48 hours and 30 days from primary PCI



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

Inclusion Criteria:

  • Age greater than 18 years old
  • ST-segment elevation myocardial infarction
  • Referred for primary PCI either within 12 h of symptom onset or between 12 and 24 h after onset with evidence of continuing ischemia

Exclusion Criteria:

  • Unconsciousness
  • Other conditions that make the patient incapable receiving integer loading dose of prasugrel
  • Any contraindication and/or known hypersensitivity or allergy to aspirin, prasugrel, intravenous unfractionated heparin, cangrelor, tirofiban
  • Any contraindication to primary PCI
  • Administration of glycoprotein IIb/IIIa inhibitors (GPI) or P2Y12-inhibitors or cangrelor < 7 days
  • Chronic dialysis
  • Recent (< 15 days) or current major bleeding
  • Recent (< 15 days) major surgery
  • Administration of fibrinolytics < 30 days
  • Current use or indication to oral anticoagulant
  • Previous stroke or transient ischemic attack (TIA)
  • Inability to follow the procedures of the study (language problems, psychological disorders, dementia) or comorbidities associated with less than 6 months survival (active malignancies drug or alcohol abuse, etc.)
  • Women who are pregnant or breast feeding or with potential to become pregnant during the course of the study (age < 55 years and last menstruation within the last 12 months) and did not undergo tubal ligation, ovariectomy or hysterectomy
  • Participation in another study with investigational drug within the 30 days preceding and during the present study
  • Enrolment of the investigator, his/her family members, employees and other dependent persons

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): NCT02978040


Contacts
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Contact: Marco Valgimigli, Prof +41 316329653 marco.valgimigli@insel.ch
Contact: Giuseppe Gargiulo, MD +41 3163227205 giuseppe.gargiulo@insel.ch

Locations
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France
Group Hospitalier Pitié-Salpetrière Not yet recruiting
Paris, France, 75013
Contact: Jean-Philippe Collet, Prof       jean-philippe.collet@aphp.fr   
Italy
University of Ferrara Not yet recruiting
Ferrara, Italy, 44124
Contact: Gianluca Campo, Prof       cmpglc@unife.it   
University of Naples Federico II Recruiting
Naples, Italy, 80131
Contact: Giovanni Esposito, Prof       espogiov@unina.it   
University of Sassari Not yet recruiting
Sassari, Italy, 07100
Contact: Guido Parodi, Prof       parodiguido@gmail.com   
Principal Investigator: Pierfranco Terrosu, MD         
Switzerland
Bern University Hospital Recruiting
Bern, Switzerland, 3010
Contact: Marco Valgimigli, Prof    +41 316329653    marco.valgimigli@insel.ch   
Contact: Giuseppe Gargiulo, MD    +41 316327205    giuseppe.gargiulo@insel.ch   
Sponsors and Collaborators
University Hospital Inselspital, Berne
Investigators
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Study Chair: Marco Valgimigli, Prof Department of Cardiology, Bern University Hospital
Principal Investigator: Giuseppe Gargiulo, MD Department of Cardiology, Bern University Hospital

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Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT02978040     History of Changes
Other Study ID Numbers: FABOLUS-FASTER
First Posted: November 30, 2016    Key Record Dates
Last Update Posted: October 24, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by University Hospital Inselspital, Berne:
Antiplatelet therapy
Cangrelor
Tirofiban
Prasugrel
Acute Myocardial Infarction
Primary Percutaneous Coronary Intervention
Pharmacokinetic/Pharmacodynamic

Additional relevant MeSH terms:
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Platelet Aggregation Inhibitors
Infarction
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Myocardial Infarction
ST Elevation Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Prasugrel Hydrochloride
Tirofiban
Cangrelor
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs