Reversing Ticagrelor's Effects With Fresh Platelets

Coronary Artery Disease Clinical Trial

Official title:

Normalizing Platelet Reactivity After Treatment With Ticagrelor

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02201394
• Other study ID #: GCO 13-1802
• Status: Completed
• Phase: Phase 4
• First received: July 24, 2014
• Last updated: October 31, 2017
• Start date: July 2014
• Est. completion date: June 2016

Study information

• Verified date: October 2017
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Acute coronary syndrome (ACS) patients treated with antiplatelet drugs who require coronary artery bypass grafting (CABG) surgery have to wait 5-7 days for the effects of the drugs to wean off. This treatment-devoid period leaves the patient vulnerable, therefore any means to shorten this period could be useful. The present study aims to investigate the possibility of reversing the antiplatelet effects of ticagrelor with the help of fresh donor platelets. Fresh platelets will be added to blood samples of treated patients in varying concentrations at specific timepoints to determine the time and amount of fresh platelets needed to normalize platelet reactivity in the treated samples.

Description:

The current American College of Cardiology/American Heart Association (ACC/AHA) guidelines for ACS patients requiring CABG surgery after treatment with dual antiplatelet therapy recommend delaying surgery for 5-7 days after discontinuation of therapy, to allow for the dissipation of its antiplatelet effects. This treatment-devoid waiting period puts the ACS patients at risk for further cardiovascular events. Any means to shorten this vulnerable period would be of critical value. One possibility to speed up the recovery of the inhibited platelets is to administer infusions of fresh platelets. In fact, platelet transfusions are frequently administered to patients during surgery who had received prior antiplatelet therapy. However, the degree to which these transfusions restore platelet function in the recipient subjects' blood and the time from dosing when they are most effective are unknown. The timing is critical in scenarios where urgent surgery is required because infusion of platelets too soon after antiplatelet dosing could render them useless by the residual drug in circulation.

The aim of the present study is to investigate the restoration of platelet function of ticagrelor-treated subjects by adding donor platelets to their blood. The study would have 2 arms mimicking different clinical scenarios:

1. Clinical Scenario 1 - Patient given a loading dose (LD) of ticagrelor in the emergency room, requires surgery: A single LD of ticagrelor (180 mg) with aspirin (325 mg) will be given to study subjects and platelet testing will be performed after addition of fresh platelets to their blood ex vivo. Donor platelets will be added at 4-, 6-, 24- and 48-hours post-dose, to assess the time required for normalizing subject's platelet function after a LD of ticagrelor.

2. Clinical Scenario 2 - Patient on maintenance dosing (MD) of ticagrelor, requires surgery: Subjects will receive ticagrelor (90 mg twice daily) with aspirin (81 mg once daily) for 3-7 days. After the last dose, platelet testing will be performed after addition of fresh platelets to their blood ex vivo, at 4-, 6-, 24- and 48-hours post-dose to assess the time required for normalizing subject's platelet function after daily treatment with ticagrelor.

Platelet testing will be carried out using the following methodologies:

1. Platelet Aggregation - VerifyNow P2Y12 assay.

2. Platelet Aggregation - Multiplate Analyzer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male or female volunteer between 18 and 75 years old.

• History of stable (i.e. non-acute) cardiovascular disease or the presence of risk factors for cardiovascular disease (i.e. hypertension, diabetes, hyperlipidemia, high calcium score and abnormal findings on angiography or stress test).

Exclusion Criteria:

• Conditions associated with hemorrhagic risk, e.g., frequent epistaxis, gastrointestinal ulcer, hemorrhagic vascular lesions, recent surgery.

• Allergy or hypersensitivity to aspirin or ticagrelor.

• Loss of >400 mL blood or blood donation within past 3 months.

• Positive serology for hepatitis B (HBs Ag) or hepatitis C.

• History of drug abuse or alcohol abuse.

• Positive pregnancy test.

• Evidence of unstable or acute cardiovascular disease (e.g., unstable angina, recent myocardial infarction, congestive heart failure).

• History of clinically relevant pulmonary, hepatic, gastrointestinal, renal, metabolic, hematologic, neurologic, respiratory or psychiatric disease, bleeding, acute infectious disease or signs of acute illness.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Ticagrelor loading dose
Single loading dose of Ticagrelor 180 mg
• Aspirin loading dose
Single loading dose of Aspirin 325 mg
• Ticagrelor maintenance dose
Ticagrelor 90 mg twice daily x 7 days
• Aspirin maintenance dose
Aspirin 81 mg once daily x 7 days

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	P2Y12 Reaction Unit (PRU)	Platelet function normalization using different concentrations (0%, 25%, 50%, and 75% supplementations) of fresh platelet within 48 hours of Ticagrelor Loading dose/last Maintenance dose, assessed using VerifyNow and expressed as P2Y12 Reaction Unit (PRU). The P2Y12 reaction unit (PRU) is an arbitrary unit of measure that represents the amount of platelet aggregation specific to the P2Y12 receptor.	Baseline (pre-treatment), 4, 6, 24 and 48 hours post Loading dose/last Maintenance dose
Primary	Platelet Aggregation Using Multiplate Analyzer	Platelet function normalization using different concentrations of fresh platelet within 48 hours of Ticagrelor Loading dose/last Maintenance dose, assessed using Multiplate Aggregometry (ADPtest), results expressed as Area Under Curve (U), where 1 U = 10 AU * min.	Baseline (pre-treatment), 4, 6, 24, and 48 hours post Loading dose/last Maintenance dose