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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2013 by Rabin Medical Center
Sponsor:
Collaborators:
Tel Aviv Medical Center
Sheba Medical Center
Meir Medical Center
Rambam Health Care Campus
Information provided by (Responsible Party):
eli lev, Rabin Medical Center
ClinicalTrials.gov Identifier:
NCT01643031
First received: July 15, 2012
Last updated: June 14, 2013
Last verified: June 2013
  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

Resource links provided by NLM:


Further study details as provided by Rabin Medical Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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
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
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)

    -

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01643031

Contacts
Contact: Hagar Medan 972-3-9376442 hagarme@clalit.org.il
Contact: Ofira Yehoshua 972-3-9376441 ofiray@clalit.org.il

Locations
Israel
Rabin Medical Center Not yet recruiting
Petah-Tikva, Israel, 49100
Contact: Hagar Medan         
Principal Investigator: Eli I Lev, MD         
Sponsors and Collaborators
Rabin Medical Center
Tel Aviv Medical Center
Sheba Medical Center
Meir Medical Center
Rambam Health Care Campus
Investigators
Principal Investigator: Eli I Lev, MD Rabin Medical Center
  More Information

Publications:
7. Feldman DN, Kim L, Rene AG, Minutello RM, Bergman G, Wong SC. Prognostic value of cardiac troponin-I or troponin-T elevation following nonemergent percutaneous coronary intervention: a meta-analysis. Catheter Cardiovasc Interv. 2011 ;77(7):1020-30
10. Price MJ, Angiolillo DJ, Teirstein PS, Lillie E, Manoukian SV, Berger PB, Tanguay JF, Cannon CP, Topol EJ. Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: a time-dependent analysis of the Gauging Responsiveness with a VerifyNow P2Y12 assay: Impact on Thrombosis and Safety (GRAVITAS) trial. Circulation. 2011 ;124(10):1132-7
11. Campo G, Parrinello G, Ferraresi P, Lunghi B, Tebaldi M, Miccoli M, Marchesini J, Bernardi F, Ferrari R, Valgimigli M. Prospective evaluation of on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention relationship with gene polymorphisms and clinical outcome. J Am Coll Cardiol. 2011 ;57(25):2474-83

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:
Coronary Artery Disease
Coronary Disease
Diabetes Mellitus
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Heart Diseases
Metabolic Diseases
Myocardial Ischemia
Vascular Diseases
Clopidogrel
Platelet Aggregation Inhibitors
Ticagrelor
Ticlopidine
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014