Pharmacodynamic and Pharmacokinetic of Switching From Cangrelor to Prasugrel in ACS Patients Undergoing PCI

NCT ID: NCT04668144

Last Updated: 2024-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 359 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-18
• Study Completion Date: 2023-05-11

Brief Summary

Cangrelor is an intravenous P2Y12 inhibitor utilized as a bridge to achieve adequate platelet inhibition until oral P2Y12 inhibitors achieve their full antiplatelet effects in patients undergoing coronary stenting. Although in this setting the potent oral P2Y12 inhibitor prasugrel is commonly utilized, there is very limited data on the optimal approach for switching between these therapies. The overarching aim of this investigation is to rule out a drug drug interaction (DDI) when cangrelor and prasugrel are concomitantly administered in patients undergoing coronary stenting.

Detailed Description

Cangrelor is an intravenous P2Y12 inhibitor utilized as a bridge to achieve adequate platelet inhibition until oral P2Y12 inhibitors achieve their full antiplatelet effects in patients undergoing coronary stenting. Although in this setting the potent oral P2Y12 inhibitor prasugrel is commonly utilized, there is very limited data on the optimal approach for switching between these therapies. In particular, ruling out a drug-drug interaction (DDI) is critical to this extent as the presence of a DDI would translate into reduced or abolished antiplatelet effects exposing these acute patients to an increased thrombotic risk. There is an unmet need to better elucidate pharmacodynamic profiles associated with the transition from cangrelor to prasugrel therapy. Of note, prasugrel has recently gone off patent and the availability of a generic formulation will favorably impact its use. Pharmacodynamic studies provide some support on the safety of administering prasugrel at the start of cangrelor infusion. However, the available data does not allow to rule out a DDI given that there was no comparator arm in which prasugrel was either given alone or at the end of cangrelor infusion. The methodological approach for this assessment should rely on comprehensive pharmacodynamics investigations aimed to assess levels of P2Y12 receptor inhibition, pharmacokinetic investigations to assess systemic levels of the drug/drug metabolite, and mechanistic investigations by assessment of levels of P2Y12 receptor gene expression. The overarching aim of this investigation is to rule out a DDI when cangrelor and prasugrel are concomitantly administered in patients undergoing coronary stenting.

Conditions

Coronary Artery Disease; Acute Coronary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Prasugrel

Prasugrel only administered at the start of PCI

Group Type: ACTIVE_COMPARATOR

Prasugrel

Intervention Type: DRUG

Prasugrel will be used in line with FDA recommendations using a 60mg LD followed by a 10mg daily maintenance dose started 24 hours after LD administration

Prasugrel + Cangrelor

Cangrelor plus prasugrel concomitantly administered at the start of PCI

Group Type: EXPERIMENTAL

Cangrelor

Intervention Type: DRUG

Cangrelor will be used at the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion. The total infusion will last 2 hours.

Prasugrel

Intervention Type: DRUG

Prasugrel will be used in line with FDA recommendations using a 60mg LD followed by a 10mg daily maintenance dose started 24 hours after LD administration

Cangrelor followed by Prasugrel

Cangrelor administered at the start of PCI plus prasugrel administered at the end of the cangrelor infusion

Group Type: ACTIVE_COMPARATOR

Cangrelor

Intervention Type: DRUG

Cangrelor will be used at the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion. The total infusion will last 2 hours.

Prasugrel

Intervention Type: DRUG

Prasugrel will be used in line with FDA recommendations using a 60mg LD followed by a 10mg daily maintenance dose started 24 hours after LD administration

Interventions

Cangrelor

Cangrelor will be used at the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion. The total infusion will last 2 hours.

Intervention Type: DRUG

Prasugrel

Prasugrel will be used in line with FDA recommendations using a 60mg LD followed by a 10mg daily maintenance dose started 24 hours after LD administration

Intervention Type: DRUG

Other Intervention Names

Kengreal; Effient

Eligibility Criteria

Inclusion Criteria

• Patients with NSTE-ACS (UA or NSTEMI) undergoing PCI. NSTE-ACS will be defined as the presence of cardiac ischemic symptoms with ischemic changes (but not ST-segment elevation) on electrocardiogram with or without a positive troponin. However, normal electrocardiograms will be acceptable if the investigator will consider an ACS presentation likely.
• Age between 18 and 75 years old

Exclusion Criteria

• Inability to provide written informed consent
• Age >75 years
• Weight <60 Kg
• ST-segment elevation myocardial infarction
• On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor) in past 7 days
• Known allergies to prasugrel or cangrelor
• Considered at high risk for bleeding
• History of ischemic or hemorrhagic stroke or transient ischemic attack
• On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban, apixaban, edoxoban)
• Planned treatment with glycoprotein IIb/IIIa inhibitors (only bailout use allowed)
• Fibrinolytics within 24 hours
• Known platelet count <80x106/mL
• Known hemoglobin <10 g/dL
• Active bleeding
• Known end stage renal disease on hemodialysis
• Known severe hepatic dysfunction
• Intubated patients (prior to randomization)
• Pregnant females [women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study]

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Scott R. MacKenzie Foundation

OTHER

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francesco Franchi, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida Jacksonville

Jacksonville, Florida, United States

Countries

United States

References

Franchi F, Rollini F, Ortega-Paz L, Been L, Giordano S, Galli M, Ghanem G, Garabedian H, Al Saleh T, Uzunoglu E, Rivas A, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Mahowald M, Reiter B, Jilma B, Angiolillo DJ. Switching From Cangrelor to Prasugrel in Patients Undergoing Percutaneous Coronary Intervention: The Switching Antiplatelet-6 (SWAP-6) Study. JACC Cardiovasc Interv. 2023 Oct 23;16(20):2528-2539. doi: 10.1016/j.jcin.2023.08.009. Epub 2023 Aug 21.

Reference Type: DERIVED

PMID: 37609698 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

SMF-02

Identifier Type: -

Identifier Source: org_study_id