Effect of Modifying Anti-platelet Treatment to Ticagrelor in Patients With Diabetes and Low Response to Clopidogrel (MATTIS-D)
Recruitment status was Not yet recruiting
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Diabetes Mellitus Coronary Disease |
Drug: Ticagrelor Drug: Continued clopidogrel |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Effect of Modifying Anti-platelet Treatment to Ticagrelor in Patients With Diabetes and Low Response to Clopidogrel |
- Rate of elevation of troponin or CK-MB (above the upper limit of normal, and above 3 times the upper limit of normal) measured 20-24 hours after the PCI. [ Time Frame: 20-24 hours after the PCI ] [ Designated as safety issue: No ]Rate of elevation of troponin or CK-MB (above the upper limit of normal, and above 3 times the upper limit of normal) measured 20-24 hours after the PCI.
- Rate of major adverse cardiovascular endpoints including death, myocardial infarction or urgent target vessel revascularization at 30 days [ Time Frame: 30 days ] [ Designated as safety issue: No ]Rate of major adverse cardiovascular endpoints including death, myocardial infarction or urgent target vessel revascularization at 30 days
| Estimated Enrollment: | 500 |
| Study Start Date: | August 2012 |
| Estimated Study Completion Date: | October 2014 |
| Estimated Primary Completion Date: | September 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Ticagrelor
Patients randomized to the ticagrelor group will receive ticagrelor at a dose of 180 mg given 1-2 hours before the coronary angiography, followed by 90 mg twice a day for 30 days after the PCI. After 30 days the patient will be invited to a special research clinic in the hospital and his treatment will be switched back to clopidogrel (to complete 1 year of treatment).
|
Drug: Ticagrelor
Ticagrelor will be given (to patients with low response to clopidogrel randomized to the Ticagrelor group) at a dose of 180 mg given 1-2 hours before the coronary angiography, followed by 90 mg twice a day for 30 days after the PCI. After 30 days the patient's treatment will be switched back to clopidogrel (to complete 1 year of treatment).
Other Name: Brilinta
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Active Comparator: Continued Clopidogrel
Patients randomized to continued clopidogrel treatment will be given an additional 300 mg of clopidogrel loading 1-2 hours before coronary angiography (in addition to the previous 300 mg load or chronic clopidogrel therapy the patient received), followed by 75 mg a day for 1 year after the PCI
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Drug: Continued clopidogrel
Patients with low response to clopidogrel randomized to continued clopidogrel treatment will be given an additional 300 mg of clopidogrel loading 1-2 hours before coronary angiography (in addition to the previous 300 mg load or chronic clopidogrel therapy the patient received), followed by 75 mg a day for 1 year after the PCI
Other Name: Plavix
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Show Detailed Description
Eligibility| Ages Eligible for Study: | 30 Years to 80 Years (Adult, Senior) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients with diabetes treated with oral hypoglycemic medications and/or insulin.
- Aged 30-80 years.
- Patients with stable angina and a positive non-invasive test, or patients with unstable angina, all planned to undergo coronary angiography.
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Treated with aspirin 75-100 mg per day.
Exclusion Criteria:
- 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.
- Any contraindications to ticagrelor or clopidogrel.
- Anemia (Hg<10 g/dL) or thrombocytopenia (<100,000 / mm3)
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Chronic renal failure (Cr ≥ 2.5 mg/dL)
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01643031
| Contact: Hagar Medan | 972-3-9376442 | hagarme@clalit.org.il | |
| Contact: Ofira Yehoshua | 972-3-9376441 | ofiray@clalit.org.il |
| Israel | |
| Rabin Medical Center | Not yet recruiting |
| Petah-Tikva, Israel, 49100 | |
| Contact: Hagar Medan | |
| Principal Investigator: Eli I Lev, MD | |
| Principal Investigator: | Eli I Lev, MD | Rabin Medical Center |
More Information
Publications:
| Responsible Party: | eli lev, Prof. Eli Lev, Director, Cardiac catheterization laboratory, Hasharon Hospital, Rabin Medical Center, Israel, Rabin Medical Center |
| ClinicalTrials.gov Identifier: | NCT01643031 History of Changes |
| Other Study ID Numbers: | 6793 |
| Study First Received: | July 15, 2012 |
| Last Updated: | June 14, 2013 |
| Health Authority: | Israel: Ethics Commission |
Keywords provided by Rabin Medical Center:
|
Diabetes Platelets aggregation inhibitors Platelet function tests |
Additional relevant MeSH terms:
|
Diabetes Mellitus Coronary Disease Coronary Artery Disease Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Myocardial Ischemia Heart Diseases Cardiovascular Diseases Vascular Diseases Arteriosclerosis Arterial Occlusive Diseases Clopidogrel Ticlopidine |
Platelet Aggregation Inhibitors Ticagrelor Purinergic P2Y Receptor Antagonists Purinergic P2 Receptor Antagonists Purinergic Antagonists Purinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Fibrinolytic Agents Fibrin Modulating Agents Cytochrome P-450 CYP2C19 Inhibitors Cytochrome P-450 Enzyme Inhibitors Enzyme Inhibitors |
ClinicalTrials.gov processed this record on September 28, 2016