Comparison of TIcagrelor and Clopidogrel in Patients With Coronary Artery diseaSe and Type 2 Diabetes Mellitus (TICS-DM) (TICS-DM)

April 13, 2016 updated by: José Luis Ferreiro, Spanish Society of Cardiology

Comparison of TIcagrelor and Clopidogrel in Patients With Coronary Artery diseaSe and Type 2 Diabetes Mellitus (TICS-DM): a Randomized Pharmacodynamic Study

Patients with type 2 diabetes mellitus (T2DM), have a high prevalence of suboptimal response to clopidogrel (up to 40%). This impaired response to antiplatelet drugs has been consistently associated with a higher risk of adverse ischemic outcomes. Different strategies have been suggested to overcome variability in response to clopidogrel and improve clinical outcomes in diabetic patients. One of these strategies is the use of newer P2Y12 inhibitors, such as ticagrelor, with more potent and consistent platelet inhibitory effects compared to clopidogrel. In summary, since patients with T2DM continue to have enhanced platelet reactivity despite the administration of commonly used dual antiplatelet therapy with aspirin and standard doses of clopidogrel, newer and more potent antiplatelet treatment strategies are warranted in this high-risk population. The purpose of the present study is to compare platelet inhibitory effects achieved with ticagrelor versus clopidogrel, both on top of aspirin therapy, in patients with type 2 DM and stable coronary artery disease.

Study Overview

Status

Status

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

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

Despite the clinical benefit associated with dual therapy consisting in aspirin and clopidogrel, there are still a considerable number of patients who continue to have atherothrombotic events. Several studies have shown a wide interindividual variability in response to clopidogrel treatment and patients with poor response have an increased risk of recurrent ischemic events. In particular, patients with type 2 diabetes mellitus (T2DM), have a high prevalence of suboptimal response to clopidogrel (up to 40%). This impaired response to antiplatelet drugs has been consistently associated with a higher risk of adverse ischemic outcomes. Different strategies have been suggested to overcome variability in response to clopidogrel and improve clinical outcomes in diabetic patients. One of these strategies is the use of newer P2Y12 inhibitors, such as ticagrelor, with more potent and consistent platelet inhibitory effects compared to clopidogrel. In summary, since patients with T2DM continue to have enhanced platelet reactivity despite the administration of commonly used dual antiplatelet therapy with aspirin and standard doses of clopidogrel, newer and more potent antiplatelet treatment strategies are warranted in this high-risk population. The purpose of the present study is to compare platelet inhibitory effects achieved with ticagrelor versus clopidogrel, both on top of aspirin therapy, in patients with type 2 DM and stable coronary artery disease (CAD).

This is a multi-center prospective, open-label, two-sequence, two-period, randomized crossover study conducted in T2DM patients between the ages of 18 and 75 years with known CAD. Subjects will be randomized in a 1:1 fashion to take ticagrelor (180-mg loading dose the first day followed by 90-mg maintenance dose) or clopidogrel (600-mg loading dose the first day followed by 75-mg daily maintenance dose) for one-week on a background of aspirin therapy (100 mg daily). After a 2-4 week washout period, subjects will cross-over treatment regimen. The washout periods are included to minimize carryover effects between treatment regimens. Patient compliance will be assessed by interview and pill counting.

Platelet function testing will be performed at the following time-points (repeated in the two periods of treatment): baseline, 2 and 24 hours after taking loading dose of the assigned drug, and 1 week after initiating the assigned drug.

All statistical comparisons of platelet function for the primary and secondary endpoints will be conducted using linear mixed-effect models with treatment, sequence, period and treatment*period (treatment by period interaction in order to test for carryover effects) as fixed effects, subject as a random effect and baseline value of the corresponding platelet function test as a covariate. A two-tailed p value of less than 0.05 will be considered to indicate a statistically significant difference for all the analyses performed.

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

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Spain
      • Madrid, Spain, 28040
        • Not yet recruiting
        • Hospital Clínico San Carlos
        • Principal Investigator:
          • David Vivas, PhD
      • Murcia, Spain, 30120
        • Not yet recruiting
        • Hospital Clínico Universitario Virgen de la Arrixaca
        • Principal Investigator:
          • Antonio Tello-Montoliu, PhD
    • Barcelona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
        • Recruiting
        • Hospital Universitari de Bellvitge - IDIBELL
        • Principal Investigator:
          • José Luis Ferreiro, MD

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:

  • Provision of informed consent prior to any study specific procedures
  • Age between 18 and 75 years
  • Type 2 DM according to ADA criteria
  • Angiographically documented CAD
  • Chronic treatment (>1 month) with aspirin (100mg/day)

Exclusion Criteria:

  • Known allergies to aspirin, clopidogrel, or ticagrelor
  • Blood dyscrasia
  • Any recent acute coronary syndrome (<30 days) or hemodinamic instability
  • Recent antiplatelet therapy (<14 days), with the exception of ASA, including: thienopyridines, cilostazol, dipiridamol, glycoprotein IIb/IIIa inhibitors
  • Oral anticoagulation with a coumarin derivative
  • Concomitant treatment with a potent CYP3A4 inhibitor (e.g. ketoconazole, claritromicine, nefazodone, ritonavir, atazanavir)
  • Any active bleeding
  • Recent history of stroke, TIA or intracranial bleeding (<6 months prior to inclusion)
  • Platelet count <100x106/microl
  • Severe chronic kidney disease (creatinine clearance measured with Cockcroft-Gault formula <30ml/min)
  • Any active neoplasm
  • Baseline ALT >2.5 times the upper limit of normality
  • Pregnant or childbearing females

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover 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: Group A

After providing written informed consent, eligible subjects will be randomized in a 1:1 fashion to group A or B.

Ticagrelor (180-mg loading dose the first day followed by 90-mg b.i.d. maintenance dose) for one week; washout period of 2-4 weeks; crossover to clopidogrel (600-mg loading dose the first day followed by 75-mg daily maintenance dose) for one-week.
Drug: Ticagrelor
Other Names:
  • Brilinta
Drug: Clopidogrel
Other Names:
  • Plavix
Experimental: Group B

After providing written informed consent, eligible subjects will be randomized in a 1:1 fashion to group A or B.

Clopidogrel (600-mg loading dose the first day followed by 75-mg daily maintenance dose) for one-week; washout period of 2-4 weeks; crossover to ticagrelor (180-mg loading dose the first day followed by 90-mg b.i.d. maintenance dose) for one week.
Drug: Ticagrelor
Other Names:
  • Brilinta
Drug: Clopidogrel
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
Platelet reactivity
Time Frame: 7 days
maximal platelet aggregation, measured with light transmittance aggregometry (using 20 μM ADP as agonist), achieved after 1 week of treatment with ticagrelor or clopidogrel
7 days

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.
Spanish Society of Cardiology

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
AstraZeneca

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: José Luis Ferreiro, Hospital Universitari de Bellvitge - IDIBELL

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

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.
April 1, 2015

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.
December 1, 2016

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.
February 1, 2017

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).
May 27, 2015

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.
May 27, 2015

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.
May 29, 2015

Study Record Updates

Last Update Posted (Estimate)

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 14, 2016

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 13, 2016

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, 2016

More Information

Terms related to this study

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.
  • ISSBRIL0162

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.

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