Clinical trial NCT02201394: Reversing Ticagrelor's Effects With Fresh Platelets
Official title: Normalizing Platelet Reactivity After Treatment With Ticagrelor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: Antiplatelet
Ticagrelor
Platelets
Thrombosis
Coronary artery disease
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2014-07-28
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: P2Y12 Reaction Unit (PRU)
timeFrame: Baseline (pre-treatment), 4, 6, 24 and 48 hours post Loading dose/last Maintenance dose
measure: Platelet Aggregation Using Multiplate Analyzer
timeFrame: Baseline (pre-treatment), 4, 6, 24, and 48 hours post Loading dose/last Maintenance dose
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Juan J Badimon, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zafar MU, Smith DA, Baber U, Sartori S, Chen K, Lam DW, Linares-Koloffon CA, Rey-Mendoza J, Jimenez Britez G, Escolar G, Fuster V, Badimon JJ. Impact of Timing on the Functional Recovery Achieved With Platelet Supplementation After Treatment With Ticagrelor. Circ Cardiovasc Interv. 2017 Aug;10(8):e005120. doi: 10.1161/CIRCINTERVENTIONS.117.005120.