Reversing Ticagrelor's Effects With Fresh Platelets

NCT02201394 | Completed Phase 4 Results DMC

• 1 other identifier: GCO 13-1802
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Artery Disease

Keywords

Antiplatelet; Ticagrelor; Platelets; Thrombosis; Coronary artery disease

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Study Arms (2)

Loading dose

EXPERIMENTAL

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

Drug: Ticagrelor loading dose; Drug: Aspirin loading dose

Maintenance dose

EXPERIMENTAL

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

Drug: Ticagrelor maintenance dose; Drug: Aspirin maintenance dose

Interventions

Ticagrelor loading dose DRUG

Single loading dose of Ticagrelor 180 mg

Also known as: Brilinta

Loading dose

Aspirin loading dose DRUG

Single loading dose of Aspirin 325 mg

Also known as: Acetylsalicylic acid, ASA

Loading dose

Ticagrelor maintenance dose DRUG

Ticagrelor 90 mg twice daily x 7 days

Also known as: Ticagrelor, Brilinta

Maintenance dose

Aspirin maintenance dose DRUG

Aspirin 81 mg once daily x 7 days

Also known as: Aspirin, ASA

Maintenance dose

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• AstraZeneca: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (1)

• 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.

  PMID: 28768756 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Thrombosis

Interventions

Ticagrelor; Aspirin

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Embolism and Thrombosis

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

Study design is partly in vitro as testing of study aims (reversing effects of antiplatelet therapy by adding fresh platelets in different concentrations and at different times) would be nearly impossible using an in vivo study design.

Results Point of Contact

• Title: Dr. Juan J. Badimon
• Organization: Atherothrombosis Research Unit, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai

Juan.Badimon@mssm.edu

Study Officials

• Juan J Badimon, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, AtheroThrombosis Research Unit; Professor of Medicine

Study Record Dates

• First Submitted: July 24, 2014
• First Posted: July 28, 2014
• Study Start: July 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: December 5, 2017
• Results First Posted: December 5, 2017

Record last verified: 2017-10

Locations

US (1)