Comparing Ticagrelor and Clopidogrel Pharmacodynamics After Thrombolysis (TACAT)

April 2, 2018 updated by: Rakesh K. Sharma, Medical Center of South Arkansas

A Randomized, Open Label, Pilot Study to Assess the Pharmacodynamics Using Vefiynow and VASP Assay; and Pharmacokinetics of Ticagrelor vs Clopidogrel in Patients Undergoing PCI With History of Fibrinolysis in 24-48 Hours

This study involves doing platelet function testing in patients who have undergone fibrinolysis. Fibrinolysis (Use of clot busting medicine in heart attack) is the standard of care to restore blood flow in blocked arteries as soon as possible after the "Heart attack" in rural health center where access to cardiac catheterization is one hour away. Fibrinolysis is done by the emergency room physician in a timely fashion to minimize the damage of the myocardium. Additionally anti-platelet regimen as adjuvant for patient undergoing fibrinolysis has been well studied in many trials. In this study investigators will use clopidogrel or ticagrelor in randomized fashion to evaluate anti- platelet effect by measuring efficacy in vivo (pharmacodynamics) and blood levels of both drugs (Pharmacokinetics).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is an open label randomized pharmacodynamics study to compare platelet function reactivity of ticagrelor and clopidogrel after PCI in sub-set of patients who have undergone fibrinolysis at least 24 hour prior to PCI..A total of 70 patients will be enrolled. Prior to enrollment, patients have already undergone fibrinolysis (selected by the treating physician), aspirin (recommended dose 324 mg) on the first day and 81 mg daily thereafter, and Lovenox or heparin as per protocol of referring ER. Patients will undergo coronary angiography as standard of care and coronary stenting if indicated. Prior to angiography patient will be enrolled in this open label randomized protocol to receive clopidogrel or ticagrelor. Patients will be randomly assigned in a 1:1 ratio by open label study to receive either clopidogrel (Plavix, Sanofi-Aventis and Bristol-Myers Squibb; a 300-mg loading dose followed by 75 mg once daily) or ticagrelor (Brilinta, AstraZeneca; 180 mg loading and 90 mg twice daily) by a computerized system of randomization. Patients will receive clopidogrel or ticagrelor daily from enrollment to discharge. For patients who did not undergo PCI after enrollment, study drugs will be administered up to and including day 8th or hospital discharge, whichever comes first. Patients will be treated as per standard of care, and pharmacodynamics and pharmacokinetic study will be carried as per protocol. VerifyNow and VASP assay will be used to measure platelet reactivity for pharmacodynamic evaluation of ticagrelor vs Clopidogrel at specific time points: baseline (time 0), 30 mins, 1 hour, 2 hours, 8 hours and at 24 hours from first oral anti-platelet dose.. Blood will be collected from the sheath or ante-cubital vein into Vacutainer tubes for platelet function assay as below by VerifyNow and VASP. VerifyNow P2Y12 Assay: VerifyNow is a turbidimetric based system that measures platelet aggregation in the whole blood.8 This instrument measures an optical signal reported as P2Y12 Reaction Units (PRU). Vasodilator-Stimulated Phosphoprotein Phosphrylation (VASP) Assay: The measure of Vasodilator-Stimulated Phosphoprotein Phosphrylation (Biocytex Inc. Marseille, France), a method to quantify P2Y12 receptor reactivity, which reflects the extent of blockade of P2Y12 receptor blockade.9 Platelet reactivity index (PRI) is calculated by measuring VASP-P levels by mean fluorescence intensity (MFI) by stimulation with prostaglandin; PGE1and PGE1 plus ADP. PRI(%)=[(MFIPGE1)-(MFIPGE1+ADP)/(MFIPGE1)]×100%. ) Pharmacokinetic will be done at 30 min, 60 min, 120 min, 4 hours, 8 hours and at 24 hours. AUC from time 0-2 hours, Cmax at 2 hours, and Tmax at 2 hours for key secondary endpoint. Will collect Cmax and Tmax at all time points to be consistent, i.e. at 0, 30 min, 1 hour, 2 hour, 8 hours, and 24 hours when you draw PD measures at those time points and sample will be shipped.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • El Dorado, Arkansas, United States, 71730
        • Medical Center of South Arkansas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Men and women 18 to 75 years of age
  2. Ischemic discomfort lasting more than 20 mins at rest within 12 hours before randomization
  3. ST-segment elevation of at least 0.1 mV in at least two contiguous limb leads, ST-segment elevation of at least 0.2 mV in at least two contiguous precordial leads, or left bundle-branch block that was not known to be old
  4. Received fibrinolytic agent, an anticoagulant (if a fibrin-specific lytic agent was prescribed) and aspirin within 24-48 hours

Exclusion Criteria:

  1. Hypersensitivity to ticagrelor or clopidogrel
  2. Active Pathological Bleeding or history of intracranial bleeding
  3. Concomitant use of oral anticoagulant
  4. Concomitant use of 40 mg of Simvastatin or lovastatin
  5. Concomitant strong CYP3A inhibitors such as ketoconazole, clarithromycin, nefazadone, ritonavir, atazanavir
  6. Concomitant use of CYP2C19 inhibitors such as omeprazole or esomeprazole
  7. Patients planned to urgent CABG
  8. Thrombocytopenia
  9. Dialysis
  10. Use of oral antiplatelet agent (ticagrelor, prasugrel, Clopidogrel) within 7 days prior to enrollment
  11. Use of GP IIb/IIIa inhibitors
  12. Rescue PCI (PCI < 24 hours from symptom onset) -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Ticagrelor
Ticagrelor Arm will be dosed with a loading dose of 180 mg followed by maintenance dose of 90 mg BID until discharge or up to 8 days.
Drug: Ticagrelor
For ticagrelor arm, randomized STEMI patients with a history of fibrinolysis within last 24-48 and undergoing PCI will be loaded with ticagrelor 180 mg prior to PCI followed by maintenance dose of 90 mg bid.
Other Names:
  • Brilinta
Active Comparator: Clopidogrel
Clopidogrel arm will be dose with a loading dose of 300 mg followed by maintenance dose of 75 mg everyday until discharge or up to 8 days.
Drug: Clopidogrel
For clopdigrel arm, randomized STEMI patients with a history of fibrinolysis within last 24-48 and undergoing PCI will be loaded with clopidogrel 300 mg prior to PCI followed by maintenance dose of 75 mg QD
Other Names:
  • Plavix

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pharmacodynamics (PRU and IPA) of ticagrelor vs Clopidogrel using VASP and VerifyNow
Time Frame: Change from baseline at 2 hours
Pharmacodynamics at baseline, 30 min, 60 min, 120 min, 4 hours, 8 hours and at 24 hours
Change from baseline at 2 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pharmacokinetic (AUC, Cmax, Tmax)
Time Frame: Change from baseline at 2 hours
Pharmacokinetics at baseline, 30 min, 60 min, 120 min, 4 hours, 8 hours and at 24 hours
Change from baseline at 2 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical Center of South Arkansas

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Rakesh K Sharma, MD, FACC, FSCAI, FSCCT, Medical Center of South Arkansas

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 2, 2014

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2015

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 27, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 28, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 29, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 4, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 2, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ISSBRIL0224

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings