Platelet Inhibition With Cangrelor and Crushed Ticagrelor in STEMI

NCT ID: NCT03247738

Last Updated: 2020-09-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-20
• Study Completion Date: 2018-12-13

Brief Summary

In STEMI patients undergoing PPCI there is a delayed onset of action of oral P2Y12 receptor inhibitors, including prasugrel and ticagrelor. Crushing prasugrel and ticagrelor improves their PK and PD profiles as it favors drug absorption and onset of antiplatelet effects and because of this, it is commonly used in STEMI patients undergoing PPCI. However, despite the use of crushed tablets, up to one-third of patients may still have high on-treatment platelet reactivity (HPR) within the first 2 hours after loading dose (LD) administration of these oral agents. Cangrelor is a potent intravenous P2Y12 receptor inhibitor with rapid onset and offset of action associated with a greater reduction in ischemic events compared with clopidogrel in P2Y12 receptor naïve patients undergoing PCI. To date most studies have explored cangrelor in the setting of PCI subjects treated with clopidogrel. The PD effects of cangrelor in STEMI patients undergoing PPCI treated with a newer generation P2Y12 receptor inhibitor and how this compares with a crushed formulation of the oral drug is unexplored. The aim of this prospective randomized study is to investigate the PD effects of cangrelor in STEMI patients undergoing PPCI treated with crushed ticagrelor.

Detailed Description

In STEMI patients undergoing PPCI there is a delayed onset of action of oral P2Y12 receptor inhibitors, including prasugrel and ticagrelor, which require more than 2 hours to exert their full antiplatelet effects, and thus exposing these high-risk patients to an increased risk of early thrombotic complications. The mechanism of this delayed onset of antiplatelet effect is likely multifactorial due to the presence in the setting of STEMI of specific conditions that translate into delayed drug absorption which in turn affect the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of oral P2Y12 receptor inhibitors. Crushing prasugrel and ticagrelor improves their PK and PD profiles as it favors drug absorption and onset of antiplatelet effects and because of this, it is commonly used in STEMI patients undergoing PPCI. However, despite the use of crushed tablets, up to one-third of patients may still have high on-treatment platelet reactivity (HPR) within the first 2 hours after loading dose (LD) administration of these oral agents. Cangrelor is a potent intravenous P2Y12 receptor inhibitor with rapid onset and offset of action associated with a greater reduction in ischemic events compared with clopidogrel in P2Y12 receptor naïve patients undergoing PCI. To date most studies have explored cangrelor in the setting of PCI subjects treated with clopidogrel and the clinical profile of cangrelor among patients treated with prasugrel or ticagrelor is currently unknown. This is noteworthy because ACS patients, in particular STEMI undergoing PPCI, are commonly treated with either prasugrel or ticagrelor. PD investigations conducted in vitro or ex vivo in stable patients have shown cangrelor to be associated with enhanced platelet inhibition compared with that induced by prasugrel and ticagrelor. However, the PD effects of cangrelor in STEMI patients undergoing PPCI treated with a newer generation P2Y12 receptor inhibitor and how this compares with a crushed formulation of the oral drug is unexplored. The aim of this prospective randomized study is to investigate the PD effects of cangrelor in STEMI patients undergoing PPCI treated with crushed ticagrelor.

Conditions

ST Segment Elevation Myocardial Infarction; Percutaneous Coronary Intervention

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cangrelor

Cangrelor will be administered as 30 μg/kg bolus followed by 4 μg/kg/min infusion for 2 hours

Group Type: EXPERIMENTAL

Cangrelor

Intervention Type: DRUG

Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.

Placebo

Normal saline bolus and infusion for 2 hours

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.

Interventions

Cangrelor

Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.

Intervention Type: DRUG

Placebo

Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.

Intervention Type: OTHER

Other Intervention Names

Kangreal

Eligibility Criteria

Inclusion Criteria

• Patients with STEMI undergoing primary PPCI
• Age > 18 years old

Exclusion Criteria

• Inability to provide written informed consent
• Known history of prior intracranial bleeding
• On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor) in the prior 10 days
• Known allergies to aspirin, ticagrelor or cangrelor
• On treatment with oral anticoagulant
• Treatment with glycoprotein IIb/IIIa inhibitors
• Fibrinolytics within 24 hours
• Active bleeding
• High risk of bleeding
• Known platelet count <80x106/mL
• Known hemoglobin <10 g/dL
• Intubated patients (prior to randomization)
• Known creatinine clearance <30 mL/minute or on hemodialysis.
• Known severe hepatic dysfunction
• Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker protection
• Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction with ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromizycin.
• Pregnant or lactating females.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chiesi Farmaceutici S.p.A.

INDUSTRY

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dominick Angiolillo, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Florida College of Medicine-Jacksonville

Locations

University of Florida

Jacksonville, Florida, United States

Countries

United States

References

Luker J, Kuhr K, Sultan A, Nolker G, Omran H, Willems S, Andrie R, Schrickel JW, Winter S, Vollmann D, Tilz RR, Jobs A, Heeger CH, Metzner A, Meyer S, Mischke K, Napp A, Fahrig A, Steinhauser S, Brachmann J, Baldus S, Mahajan R, Sanders P, Steven D. Internal Versus External Electrical Cardioversion of Atrial Arrhythmia in Patients With Implantable Cardioverter-Defibrillator: A Randomized Clinical Trial. Circulation. 2019 Sep 24;140(13):1061-1069. doi: 10.1161/CIRCULATIONAHA.119.041320. Epub 2019 Aug 30.

Reference Type: DERIVED

PMID: 31466479 (View on PubMed)

Franchi F, Rollini F, Rivas A, Wali M, Briceno M, Agarwal M, Shaikh Z, Nawaz A, Silva G, Been L, Smairat R, Kaufman M, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Bass TA, Angiolillo DJ. Platelet Inhibition With Cangrelor and Crushed Ticagrelor in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. Circulation. 2019 Apr 2;139(14):1661-1670. doi: 10.1161/CIRCULATIONAHA.118.038317.

Reference Type: DERIVED

PMID: 30630341 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IIS CHI001 WIRB

Identifier Type: -

Identifier Source: org_study_id