Clinical trial NCT02978040: Randomized Comparison of Cangrelor, Tirofiban and Prasugrel in Patients With STEMI Referred for Primary PCI.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
STEMI - ST Elevation Myocardial Infarction
Keywords: Antiplatelet therapy
Cangrelor
Tirofiban
Prasugrel
Acute Myocardial Infarction
Primary Percutaneous Coronary Intervention
Pharmacokinetic/Pharmacodynamic
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2016-11-30
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Inhibition of platelet activity (IPA, %) with LTA-ADP 20 µmol/l
timeFrame: 30 minutes
Secondary outcomes:
measure: Inhibition of platelet activity (IPA, %) with LTA-ADP 20 µmol/l
timeFrame: 15 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours
measure: Inhibition of platelet activity (IPA, %) with LTA-ADP 5 µmol/l
timeFrame: 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours
measure: Inhibition of platelet activity (IPA, %) with LTA-TRAP 5 µmol/l
timeFrame: 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours
measure: Inhibition of platelet activity (IPA, %) with LTA-TRAP 15 µmol/l
timeFrame: 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours
measure: Area under the curve (AUC) at Multiplate with ADP test
timeFrame: 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours
measure: Area under the curve (AUC) at Multiplate with TRAP test
timeFrame: 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours
measure: Angiographic result
timeFrame: immediately after PCI procedure
measure: Electrocardiographic result
timeFrame: immediately after PCI procedure and 90 minutes after PCI
measure: Infarct size at Cardiac Magnetic Resonance Imaging (MRI)
timeFrame: 3 days and 4-6 months after PCI
measure: Intramyocardial haemorrhage at Cardiac Magnetic Resonance Imaging (MRI)
timeFrame: 3 days and 4-6 months after PCI
measure: Major adverse ischemic clinical events
timeFrame: 48 h and 30 days after PCI
measure: Bleeding events
timeFrame: 48 h and 30 days after PCI
Other outcomes:
Locations:
city: Ferrara
country: Italy
facility: University of Ferrara
city: Naples
country: Italy
facility: University of Naples Federico II
city: Bern
country: Switzerland
facility: Bern University Hospital
Study officials:
affiliation: Department of Cardiology, Bern University Hospital
name: Marco Valgimigli, Prof
role: STUDY_CHAIR
affiliation: Department of Cardiology, Bern University Hospital
name: Giuseppe Gargiulo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gargiulo G, Esposito G, Avvedimento M, Nagler M, Minuz P, Campo G, Gragnano F, Manavifar N, Piccolo R, Tebaldi M, Cirillo P, Hunziker L, Vranckx P, Leonardi S, Heg D, Windecker S, Valgimigli M. Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment-Elevation Myocardial Infarction: Primary Results of the FABOLUS-FASTER Trial. Circulation. 2020 Aug 4;142(5):441-454. doi: 10.1161/CIRCULATIONAHA.120.046928. Epub 2020 Jun 27.
citation: Gargiulo G, Esposito G, Cirillo P, Nagler M, Minuz P, Campo G, Gragnano F, Manavifar N, Piccolo R, Avvedimento M, Tebaldi M, Wahl A, Hunziker L, Billinger M, Heg D, Windecker S, Valgimigli M. 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: Design and Rationale : The FABOLUS FASTER Trial. J Cardiovasc Transl Res. 2021 Feb;14(1):110-119. doi: 10.1007/s12265-020-09969-4. Epub 2020 Feb 24.