Effect of Modifying Anti-platelet Treatment to Ticagrelor in Patients With Diabetes and Low Response to Clopidogrel

• Status: Unknown status
• Trial end date: 2014-10-01
• Target enrollment: 0
• Participant gender: All

Summary

In recent years numerous studies have shown that the response of patients to the anti-platelet drug clopidogrel is widely variable. Furthermore, patients who do not respond well to the drug ("resistant") have been shown to be at increased risk to develop cardiac events, including myocardial infarction and mortality. It thus seems reasonable to test the efficacy of the drug (by platelet function tests) and modify treatment accordingly. However, a large study that examined a strategy of routine testing of clopidogrel response in thousands of patients (GRAVITAS study) did not show any clinical benefit. This study was limited, however, by a very low event rate (2.3%), and by the strategy employed to treat patients with low response (increasing the clopidogrel dose), which is currently known to be ineffective in many patients with low response. To overcome these limitations the investigators plan to examine a high risk population - patients with diabetes planned to undergo coronary angiography - and to treat clopidogrel low responders by switching their treatment to the potent anti-platelet drug ticagrelor, which has been shown to overcome clopidogrel low response.

The investigators hypothesize that patients with diabetes and low response to clopidogrel will benefit clinically from switching therapy to ticagrelor. The main endpoint of the study will be the risk of myocardial enzyme elevation following percutaneous coronary intervention (PCI); a marker which has been strongly associated with poor clinical outcome.

The aim of the study is, therefore, to assess whether a strategy of monitoring platelet function during clopidogrel treatment in patients with diabetes undergoing PCI, and modifying treatment to ticagrelor in patients with low response, will be associated with reduced risk of myocardial enzyme release.

The investigators plan to enroll patients with treated diabetes, planned to undergo coronary angiography. Patients with acute or recent myocardial infarction will be excluded. They will be tested for response to clopidogrel by the VerifyNow P2Y12 assay (either on chronic clopidogrel treatment or 12-24 hours after receiving 300 mg clopidogrel). Patients with low response to clopidogrel (≥ 208 PRU) will be randomized to either continued treatment with clopidogrel (75 mg/day), or switching of treatment to ticagrelor (90 mg twice a day) for 30 days (followed by continued clopidogrel therapy). The primary endpoint will be the rate of troponin of CK-MB (cardiac enzymes) measured 20-24 hours after the PCI. Secondary endpoints will be the occurrence of adverse clinical endpoints - myocardial infarction, need for urgent revascularization or mortality at 30 days. The investigators aim to enroll 100 patients in each study group (ticagrelor vs. continued clopidogrel). Assuming a clopidogrel low response rate of 40% among patients with diabetes, about 500 patients would have to be screened to identify 200 patients with low response.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rabin Medical Center
• Collaborators: Meir Medical Center; Rambam Health Care Campus; Sheba Medical Center; Tel Aviv Medical Center
• Treatments: Clopidogrel; Platelet Aggregation Inhibitors; Ticagrelor; Ticlopidine

Criteria

Inclusion Criteria:

1. Patients with diabetes treated with oral hypoglycemic medications and/or insulin.

2. Aged 30-80 years.

3. Patients with stable angina and a positive non-invasive test, or patients with unstable angina, all planned to undergo coronary angiography.

4. Treated with aspirin 75-100 mg per day.

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Exclusion Criteria:

1. Any myocardial infarction (STEMI or non-STEMI) as the indication for the cardiac catheterization. Thus, only troponin-negative and CK-MB negative patients will be included.

2. Any contraindications to ticagrelor or clopidogrel.

3. Anemia (Hg<10 g/dL) or thrombocytopenia (<100,000 / mm3)

4. Chronic renal failure (Cr ≥ 2.5 mg/dL)

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