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Reversing Ticagrelor's Effects With Fresh Platelets

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ClinicalTrials.gov Identifier: NCT02201394
Recruitment Status : Completed
First Posted : July 28, 2014
Results First Posted : December 5, 2017
Last Update Posted : December 5, 2017
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Juan J Badimon, Icahn School of Medicine at Mount Sinai

Brief 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.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Drug: Ticagrelor loading dose Drug: Aspirin loading dose Drug: Ticagrelor maintenance dose Drug: Aspirin maintenance dose Phase 4

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Normalizing Platelet Reactivity After Treatment With Ticagrelor
Study Start Date : July 2014
Actual Primary Completion Date : June 2016
Actual Study Completion Date : June 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Loading dose
Patients with stable CVD given a single ticagrelor loading dose and aspirin loading dose
Drug: Ticagrelor loading dose
Single loading dose of Ticagrelor 180 mg
Other Name: Brilinta

Drug: Aspirin loading dose
Single loading dose of Aspirin 325 mg
Other Names:
  • Acetylsalicylic acid
  • ASA

Experimental: Maintenance dose
Patients with stable CVD given ticagrelor maintenance dose and aspirin maintenance dose for one week.
Drug: Ticagrelor maintenance dose
Ticagrelor 90 mg twice daily x 7 days
Other Names:
  • Ticagrelor
  • Brilinta

Drug: Aspirin maintenance dose
Aspirin 81 mg once daily x 7 days
Other Names:
  • Aspirin
  • ASA




Primary Outcome Measures :
  1. P2Y12 Reaction Unit (PRU) [ Time Frame: Baseline (pre-treatment), 4, 6, 24 and 48 hours post Loading dose/last Maintenance dose ]
    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.

  2. Platelet Aggregation Using Multiplate Analyzer [ Time Frame: Baseline (pre-treatment), 4, 6, 24, and 48 hours post Loading dose/last Maintenance dose ]
    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.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02201394


Locations
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United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
AstraZeneca
Investigators
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Principal Investigator: Juan J Badimon, PhD Icahn School of Medicine at Mount Sinai

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Juan J Badimon, Director, AtheroThrombosis Research Unit; Professor of Medicine, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT02201394     History of Changes
Other Study ID Numbers: GCO 13-1802
First Posted: July 28, 2014    Key Record Dates
Results First Posted: December 5, 2017
Last Update Posted: December 5, 2017
Last Verified: October 2017
Keywords provided by Juan J Badimon, Icahn School of Medicine at Mount Sinai:
Antiplatelet
Ticagrelor
Platelets
Thrombosis
Coronary artery disease
Additional relevant MeSH terms:
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Aspirin
Platelet Aggregation Inhibitors
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Ticagrelor
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents