Clinical trial NCT02201394
Conditions: Coronary Artery Disease
Keywords: Antiplatelet Ticagrelor Platelets Thrombosis Coronary artery disease
Sponsor: Icahn School of Medicine at Mount Sinai
Start date: 2014-07-01; Completion date: 2016-06-01
Enrollment: 20 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: Patients with stable CVD given a single ticagrelor loading dose and aspirin loading dose arm 2: Patients with stable CVD given ticagrelor maintenance dose and aspirin maintenance dose for one week.
Interventions: intervention 1: Ticagrelor loading dose intervention 2: Aspirin loading dose intervention 3: Ticagrelor maintenance dose intervention 4: Aspirin maintenance dose
Intervention descriptions: intervention 1: Single loading dose of Ticagrelor 180 mg intervention 2: Single loading dose of Aspirin 325 mg intervention 3: Ticagrelor 90 mg twice daily x 7 days intervention 4: Aspirin 81 mg once daily x 7 days

Protocol documents: