Low Maintenance Dose Ticagrelor Versus Clopidogrel in Diabetes Patients Undergoing PCI
Condition: Diabetes Mellitus, Type 2; Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Ticagrelor; Clopidogrel
Intervention description: After providing written informed consent and following diagnostic angiography, patients meeting study entry criteria undergoing PCI will be randomly assigned in a 1:1 ratio to treatment with either ticagrelor or clopidogrel. Randomized treatment will be maintained for 30±3 days.; After providing written informed consent and following diagnostic angiography, patients meeting study entry criteria undergoing PCI will be randomly assigned in a 1:1 ratio to treatment with either ticagrelor or clopidogrel. Randomized treatment will be maintained for 30±3 days.
Intervention MeSH terms: Clopidogrel; Ticagrelor
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Prospective randomized
Masking: None (Open Label)
Masking description: Staff performing PK/PD assessments will remain blinded to treatment assignment.
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: diabetes mellitus; percutaneous coronary intervention; ticagrelor; clopidogrel; coronary artery disease

Summary:

      To date there is very little PD and pharmacokinetic (PK) data on the ticagrelor 60 mg bid
      dosing regimen. In particular, there is no prospective PK/PD study on this dosing regimen in
      patients with DM who are known to have impaired response to clopidogrel therapy. Since DM
      patients frequently require elective PCI due to chronic progression of CAD (and not solely
      because of an acute thrombotic complication), and clopidogrel remains the guideline
      recommended P2Y12 inhibiting therapy for these patients, understanding the PD effects of the
      ticagrelor 60 mg bid regimen in this setting is an unmet clinical need. This is also in light
      of the ongoing THEMIS trial which is specifically evaluating the impact of the ticagrelor 60
      mg bid dosing regimen in type 2 DM patients without a prior major CV event.
    

Eligibility criteria:

        Inclusion criteria:

          1. Provision of informed consent prior to any study specific procedures

          2. Men or women ≥18 years of age

          3. Diagnosed with type 2 DM defined by ongoing glucose lowering drug (oral medications
             and / or insulin) treatment for at least 1 month

          4. Presence of CAD undergoing elective PCI* * Patients will need to be cardiac
             enzyme-negative prior to undergoing coronary angiography. Patient will need to be on a
             background of aspirin therapy (treated with a 325 mg LD prior to coronary angiography
             unless already on chronic low-dose aspirin therapy). Patients on maintenance
             clopidogrel 75 mg therapy for at least 1 week due to a prior vascular intervention
             will also be eligible. However, patients on clopidogrel, ticagrelor or prasugrel due
             to a prior acute major cardiovascular event (MI or stroke) will not be eligible.

        Exclusion criteria:

          1. Previous MI (with the exception of definite non-type 1 MI [eg, due to coronary
             revascularization procedure, profound hypotension, hypertensive emergency,
             tachycardia, or profound anemia])

          2. Previous stroke (transient ischemic attack [TIA] is not included in the stroke
             definition)

          3. Use of an intravenous antiplatelet therapy (i.e., cangrelor or GPI) during PCI

          4. On treatment with clopidogrel, prasugrel, or ticagrelor due to a prior acute major CV
             event (MI or stroke) (on treatment with clopidogrel due to prior vascular intervention
             not secondary to a major CV event is allowed)

          5. Planned use of aspirin treatment at doses >100 mg od

          6. Anticipated concomitant oral or intravenous therapy with strong cytochrome P450 3A4
             (CYP3A4) inhibitors or CYP3A4 substrates with narrow therapeutic indices that cannot
             be stopped for the course of the study:

               -  Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin,
                  clarithromycin (but not erythromycin or azithromycin), nefazadone, ritonavir,
                  saquinavir, nelfinavir, indinavir, atanazavir

               -  CYP3A4 substrates with narrow therapeutic index: quinidine, simvastatin at doses
                  >40 mg daily or lovastatin at doses >40 mg daily

          7. Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin
             (at venous thrombosis treatment not prophylaxis doses)

          8. Patients with known bleeding diathesis or coagulation disorder

          9. History of previous intracerebral bleed at any time, gastrointestinal (GI) bleed
             within the past 6 months prior to randomization, or major surgery within 30 days prior
             to randomization

         10. Active pathological bleeding

         11. Hypersensitivity to ticagrelor and clopidogrel or any of the excipients

         12. Increased risk of bradycardic events (eg, known sick sinus syndrome, second or third
             degree AV block or previous documented syncope suspected to be due to bradycardia)
             unless treated with a pacemaker

         13. Known severe liver disease (eg, ascites and/or clinical signs of coagulopathy)

         14. Renal failure requiring dialysis

         15. Known platelet count <80x106/mL

         16. Known hemoglobin <9 g/dL

         17. Women of child-bearing potential (ie, those who are not chemically or surgically
             sterilized or who are not post-menopause) who are not willing to use a medically
             accepted method of contraception that is considered reliable in the judgment of the
             investigator OR who have a positive pregnancy test at enrolment or randomization OR
             women who are breast-feeding. If a subject becomes pregnant during the course of the
             study the investigational product should be discontinued immediately [the outcome of
             all pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy,
             normal birth or congenital abnormality) will be followed up and documented even if the
             subject was discontinued from the study].

         18. Inability of the patient to understand and/or comply with study procedures and/or
             follow up, in the opinion of the investigator, OR any conditions that, in the opinion
             of the investigator, may render the patient unable to complete the study

         19. Life expectancy of less than 1 month based on investigator's judgement

         20. Participation in another clinical study with an investigational (defined as non-FDA
             approved) product within 28 days prior to enrolment

         21. Previous randomization in the present study