Reversing Ticagrelor's Effects With Fresh Platelets

NCT ID: NCT02201394

Last Updated: 2017-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2016-06-30

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.

Conditions

Coronary Artery Disease

Keywords

Antiplatelet; Ticagrelor; Platelets; Thrombosis; Coronary artery disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Loading dose

Patients with stable CVD given a single ticagrelor loading dose and aspirin loading dose

Group Type: EXPERIMENTAL

Ticagrelor loading dose

Intervention Type: DRUG

Single loading dose of Ticagrelor 180 mg

Aspirin loading dose

Intervention Type: DRUG

Single loading dose of Aspirin 325 mg

Maintenance dose

Patients with stable CVD given ticagrelor maintenance dose and aspirin maintenance dose for one week.

Group Type: EXPERIMENTAL

Ticagrelor maintenance dose

Intervention Type: DRUG

Ticagrelor 90 mg twice daily x 7 days

Aspirin maintenance dose

Intervention Type: DRUG

Aspirin 81 mg once daily x 7 days

Interventions

Ticagrelor loading dose

Single loading dose of Ticagrelor 180 mg

Intervention Type: DRUG

Aspirin loading dose

Single loading dose of Aspirin 325 mg

Intervention Type: DRUG

Ticagrelor maintenance dose

Ticagrelor 90 mg twice daily x 7 days

Intervention Type: DRUG

Aspirin maintenance dose

Aspirin 81 mg once daily x 7 days

Intervention Type: DRUG

Other Intervention Names

Brilinta; Acetylsalicylic acid; ASA; Ticagrelor; Brilinta; Aspirin; ASA

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Juan J Badimon

Director, AtheroThrombosis Research Unit; Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Juan J Badimon, PhD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 28768756 (View on PubMed)

Other Identifiers

GCO 13-1802

Identifier Type: -

Identifier Source: org_study_id