Randomized Comparison of Cangrelor, Tirofiban and Prasugrel in Patients With STEMI Referred for Primary PCI.

NCT02978040 | Completed Phase 4 DMC

• 1 other identifier: FABOLUS-FASTER
• Study Type: interventional
• Target: 122
• Locations: 2 countries
• Sites: 3

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.

Conditions

Coronary Artery Disease; STEMI - ST Elevation Myocardial Infarction

Keywords

Antiplatelet therapy; Cangrelor; Tirofiban; Prasugrel; Acute Myocardial Infarction; Primary Percutaneous Coronary Intervention; Pharmacokinetic/Pharmacodynamic

Outcome Measures

Primary Outcomes (1)

• Inhibition of platelet activity (IPA, %) with LTA-ADP 20 µmol/l

  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

  30 minutes

Secondary Outcomes (12)

• Inhibition of platelet activity (IPA, %) with LTA-ADP 20 µmol/l

  15 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours

• Inhibition of platelet activity (IPA, %) with LTA-ADP 5 µmol/l

  15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours

• Inhibition of platelet activity (IPA, %) with LTA-TRAP 5 µmol/l

  15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours

• Inhibition of platelet activity (IPA, %) with LTA-TRAP 15 µmol/l

  15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours

• Area under the curve (AUC) at Multiplate with ADP test

  15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4-6 hours

Study Arms (3)

Cangrelor

EXPERIMENTAL

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

Tirofiban

ACTIVE COMPARATOR

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

Prasugrel

ACTIVE COMPARATOR

Prasugrel oral integer or chewed at an identical loading dose of 60 mg

Drug: Prasugrel

Interventions

Cangrelor DRUG

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).

Also known as: Kengreal, Kengrexal

Cangrelor

Tirofiban DRUG

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) .

Also known as: Aggrastat

Tirofiban

Prasugrel DRUG

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).

Also known as: Efient

Prasugrel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (3)

University of Ferrara

Ferrara, 44124, Italy

Location

University of Naples Federico II

Naples, 80131, Italy

Location

Bern University Hospital

Bern, 3010, Switzerland

Location

Related Publications (3)

• Minuz P, Giorgetti A, Meneguzzi A, Taus F, Ribeiro RP, Baldessari F, Gargiulo G, Gragnano F, Landi A, Castelli M, Gottardo R, Bortolotti F, Verlato G, Fava C, Cattaneo M, Tagliaro F, Valgimigli M. Prasugrel Intermediate Metabolite Modulates Platelet Inhibition by Negatively Interfering With an Active Metabolite: An Ex Vivo, In Vitro, and In Silico Study. Arterioscler Thromb Vasc Biol. 2025 May;45(5):792-804. doi: 10.1161/ATVBAHA.124.321916. Epub 2025 Mar 20.

  PMID: 40109258 DERIVED

• 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.

  PMID: 32795098 DERIVED

• 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.

  PMID: 32096064 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; ST Elevation Myocardial Infarction

Interventions

cangrelor; Tirofiban; Prasugrel Hydrochloride

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Tyrosine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Marco Valgimigli, Prof

  Department of Cardiology, Bern University Hospital

  STUDY CHAIR

• Giuseppe Gargiulo, MD

  Department of Cardiology, Bern University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2016
• First Posted: November 30, 2016
• Study Start: July 4, 2017
• Primary Completion: August 26, 2019
• Study Completion: December 27, 2019
• Last Updated: February 21, 2020

Record last verified: 2020-02

Locations

IT (2); CH (1)