Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 76 of 1311 for:    ASPIRIN AND Platelet Aggregation

Reversing Ticagrelor's Effects With Fresh Platelets

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE July 24, 2014
First Posted Date  ICMJE July 28, 2014
Results First Submitted Date  ICMJE September 26, 2017
Results First Posted Date  ICMJE December 5, 2017
Last Update Posted Date December 5, 2017
Study Start Date  ICMJE July 2014
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 31, 2017)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 24, 2014)
  • Platelet reactivity [ Time Frame: Baseline (pre-treatment) ]
    Platelet reactivity assessed using VerifyNow P2Y12 assay (P2Y12 Reactivity Units -PRU)
  • Platelet reactivity [ Time Frame: 4-hour post-dose ]
    Platelet reactivity assessed using VerifyNow P2Y12 assay (P2Y12 Reactivity Units -PRU)
  • Platelet reactivity [ Time Frame: 6-hour post-dose ]
    Platelet reactivity assessed using VerifyNow P2Y12 assay (P2Y12 Reactivity Units -PRU)
  • Platelet reactivity [ Time Frame: 24-hour post-dose ]
    Platelet reactivity assessed using VerifyNow P2Y12 assay (P2Y12 Reactivity Units -PRU)
  • Platelet reactivity [ Time Frame: 48-hour post-dose ]
    Platelet reactivity assessed using VerifyNow P2Y12 assay (P2Y12 Reactivity Units -PRU)
Change History Complete list of historical versions of study NCT02201394 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: July 24, 2014)
  • Platelet aggregation [ Time Frame: Baseline (pre-treatment) ]
    Platelet aggregation assessed using Multiplate Analyzer
  • Platelet aggregation [ Time Frame: 4-hour post-dose ]
    Platelet aggregation assessed using Multiplate Analyzer
  • Platelet aggregation [ Time Frame: 6-hour post-dose ]
    Platelet aggregation assessed using Multiplate Analyzer
  • Platelet aggregation [ Time Frame: 24-hour post-dose ]
    Platelet aggregation assessed using Multiplate Analyzer
  • Platelet aggregation [ Time Frame: 48-hour post-dose ]
    Platelet aggregation assessed using Multiplate Analyzer
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Reversing Ticagrelor's Effects With Fresh Platelets
Official Title  ICMJE Normalizing Platelet Reactivity After Treatment With Ticagrelor
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Coronary Artery Disease
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • Experimental: Loading dose
    Patients with stable CVD given a single ticagrelor loading dose and aspirin loading dose
    Interventions:
    • Drug: Ticagrelor loading dose
    • Drug: Aspirin loading dose
  • Experimental: Maintenance dose
    Patients with stable CVD given ticagrelor maintenance dose and aspirin maintenance dose for one week.
    Interventions:
    • Drug: Ticagrelor maintenance dose
    • Drug: Aspirin maintenance dose
Publications * 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). pii: e005120. doi: 10.1161/CIRCINTERVENTIONS.117.005120. Erratum in: Circ Cardiovasc Interv. 2017 Sep;10(9):.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 13, 2016)
20
Original Estimated Enrollment  ICMJE
 (submitted: July 24, 2014)
40
Actual Study Completion Date  ICMJE June 2016
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02201394
Other Study ID Numbers  ICMJE GCO 13-1802
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Juan J Badimon, Icahn School of Medicine at Mount Sinai
Study Sponsor  ICMJE Icahn School of Medicine at Mount Sinai
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE
Principal Investigator: Juan J Badimon, PhD Icahn School of Medicine at Mount Sinai
PRS Account Icahn School of Medicine at Mount Sinai
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP