PD and PK Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-treatment

NCT04634162 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: SMF-01
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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 ticagrelor is commonly utilized, there is very limited data on the optimal approach for switching between these therapies. The methodological approach for this assessment should rely on comprehensive pharmacodynamics (PD) investigations aimed to assess levels of P2Y12 receptor inhibition, pharmacokinetic (PK) 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 drug-drug interaction when ticagrelor is administered prior to cangrelor infusion.

Conditions

Coronary Artery Disease

Keywords

ticagrelor; cangrelor; switching

Outcome Measures

Primary Outcomes (1)

• Platelet Reactivity Measured by VerifyNow

  The primary end point of the study will be the non-inferiority in P2Y12 reaction units (PRU) measured by VerifyNow after discontinuation of cangrelor vs. placebo

  2 hours

Study Arms (2)

Cangrelor

EXPERIMENTAL

Ticagrelor loading dose followed after 1 hour by cangrelor bolus and infusion

Drug: Cangrelor; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Ticagrelor loading dose followed after 1 hour by placebo infusion

Drug: Cangrelor; Drug: Placebo

Interventions

Cangrelor DRUG

Cangrelor will be used at the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion. The duration of cangrelor/placebo infusion will be 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase

Also known as: Kengreal

Cangrelor; Placebo

Placebo DRUG

Normal saline will be infused for 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase

Also known as: Normal saline

Cangrelor; Placebo

Eligibility Criteria

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

You may qualify if:

• Patients with known coronary artery disease (defined as prior type I myocardial infarction, coronary revascularization, percutaneous or surgical, or presence of at least a 50% stenosis in any major epicardial vessel).
• Age \> 18 years old
• On aspirin 81mg/qd for at least 1 month

You may not qualify if:

• Inability to provide written informed consent
• Hemodynamic instability
• On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor) in past 30 days
• Known allergies to ticagrelor or cangrelor
• Considered at high risk for bleeding
• History of intracranial bleeding/hemorrhagic stroke
• On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban, apixaban, edoxoban) within past 30 days
• Known platelet count \<80x106/mL
• Known hemoglobin \<10 g/dL
• Active bleeding
• Known end stage renal disease on hemodialysis
• Known severe hepatic dysfunction
• Acute or severe bronchial asthma or upper airway obstruction.
• 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.

Sponsors & Collaborators

• University of Florida: lead
• Scott R. MacKenzie Foundation: collaborator

Study Sites (1)

University of Florida Jacksonville

Jacksonville, Florida, 32209, United States

Location

Related Publications (1)

• Franchi F, Ortega-Paz L, Rollini F, Galli M, Been L, Ghanem G, Shalhoub A, Ossi T, Rivas A, Zhou X, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Reiter B, Jilma B, Angiolillo DJ. Cangrelor in Patients With Coronary Artery Disease Pretreated With Ticagrelor: The Switching Antiplatelet (SWAP)-5 Study. JACC Cardiovasc Interv. 2023 Jan 9;16(1):36-46. doi: 10.1016/j.jcin.2022.10.034. Epub 2022 Oct 31.

  PMID: 36317958 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

cangrelor; Saline Solution

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Francesco Franchi, MD
• Organization: Division of Cardiology University of Florida College of Medicine - Jacksonville

francesco.franchi@jax.ufl.edu

1-904-244-2060

Study Officials

• Francesco Franchi, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients, research staff and laboratory personnel will be blinded to treatment assignments. Masking and randomization of medications (cangrelor and placebo) will be performed by our institutional research pharmacy.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The Switching Antiplatelet Therapy-5 (SWAP-5) study will be a prospective, randomized, double-blind, placebo controlled, cross-over PK and PD investigation

Study Record Dates

• First Submitted: November 16, 2020
• First Posted: November 18, 2020
• Study Start: February 9, 2021
• Primary Completion: August 16, 2021
• Study Completion: November 30, 2021
• Last Updated: May 16, 2023
• Results First Posted: May 16, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)