Pharmacodynamic and Pharmacokinetic of Switching From Cangrelor to Prasugrel in ACS Patients Undergoing PCI (SWAP-6)

Pharmacodynamic and Pharmacokinetic Profiles on Switching From Cangrelor to Prasugrel in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: The Switching Antiplatelet -6 (SWAP-6) Study

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Acute Coronary Syndrome
• Intervention / Treatment: Drug: Prasugrel; Drug: Cangrelor

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.

• Study Type: Interventional
• Enrollment (Actual): 359
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida Jacksonville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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]

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Prasugrel; Prasugrel only administered at the start of PCI	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; Other Names: Effient
Experimental: Prasugrel + Cangrelor; Cangrelor plus prasugrel concomitantly administered at the start of PCI	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; Other Names: Effient; Drug: 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.; Other Names: Kengreal
Active Comparator: Cangrelor followed by Prasugrel; Cangrelor administered at the start of PCI plus prasugrel administered at the end of the cangrelor infusion	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; Other Names: Effient; Drug: 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.; Other Names: Kengreal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet Reactivity Measured by VerifyNow	The primary end point of the study will be the non-inferiority in P2Y12 reaction units (PRU) of cangrelor plus prasugrel concomitantly administered at the start of PCI versus prasugrel only administered at the start of PCI.	4 hours

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Scott R. MacKenzie Foundation
• Investigators: Principal Investigator: Francesco Franchi, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2021
• Primary Completion (Actual): February 2, 2023
• Study Completion (Actual): May 11, 2023

Study Registration Dates

• First Submitted: December 9, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 16, 2020

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Disease; Coronary Disease; Coronary Artery Disease; Syndrome; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Prasugrel Hydrochloride; Cangrelor
• Other Study ID Numbers: SMF-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No