Study of Effects of Ticagrelor on Microparticles and Micro-RNA in NSTE-ACS (TIGER-M)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Catholic University of the Sacred Heart
Sponsor:
Information provided by (Responsible Party):
L.M. Biasucci, Catholic University of the Sacred Heart
ClinicalTrials.gov Identifier:
NCT02071966
First received: February 21, 2014
Last updated: February 25, 2014
Last verified: February 2014
  Purpose

The aim of the study is to learn more about the pathophysiology of acute coronary syndrome (ACS) and to evaluate the mechanisms responsible of the action and benefits of ticagrelor.

Ticagrelor is an oral and reversible inhibitor of P2Y12 receptor. Few information is available about the action of ticagrelor on the molecules involved in thrombogenesis and platelets activation in ACS.

The aim of this study is to evaluate the mechanisms of ticagrelor action in vivo.

It was observed that patients with myocardial infarction have higher blood levels of microparticles than patients with unstable angina or stable angina.

The investigators assumed that ticagrelor benefits are represented by a reduction of microparticle levels, a marker of endothelial dysfunction in patients with cardiovascular disease, and by a modification in microRNAs pattern, fragments of mRNA that have a regulatory action in various cellular processes (such as proliferation, differentiation, growth and cellular death) and represent new biomarkers in ACS.


Condition Intervention Phase
Non ST Segment Elevation Acute Coronary Syndrome
Drug: Ticagrelor
Drug: Clopidogrel
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of TIcaGREloR on Circulating Microparticles and Micro-RNAs in Patients With Non ST Elevation Acute Coronary Syndromes

Resource links provided by NLM:


Further study details as provided by Catholic University of the Sacred Heart:

Primary Outcome Measures:
  • Micro-RNA and microparticles [ Time Frame: up to three months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 64
Study Start Date: November 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ticagrelor
Ticagrelor: oral, 180 mg once for the first dose then 90 mg twice a day
Drug: Ticagrelor
Comparison of Ticagrelor with another anti-platelet drug (Clopidogrel)
Other Name: Brilique
Active Comparator: Clopidogrel
Clopidogrel: oral, 300 or 600 mg once for the first dose, 75 mg once a day
Drug: Clopidogrel
Comparison of Clopidogrel with another anti-platelet drug (Ticagrelor)
Other Name: Plavix

Detailed Description:

Ticagrelor is an oral, reversibly binding P2Y12 receptor inhibitor that yields, in a dose-dependent fashion, greater and more consistent inhibition of platelet aggregation than standard regimens of clopidogrel in patients with stable atherosclerotic disease and ACS. However, little information is available regarding its complex effect on thrombogenesis and platelet activation in acute coronary syndromes setting. It has been widely demonstrated the potential role of MP in several biologic processes known to take part to pathophysiology of coronary syndromes, such as inflammation, coagulation and apoptosis. Recent studies focused on miRNAs' regulatory activity of several cellular processes, such as proliferation, differentiation, development, and cell death, and on their role as biomarkers in ACS. The investigators suppose that the observed major efficacy of ticagrelor is related to its actions on MP and microRNAs. Considering the major clinical effectiveness shown by ticagrelor in comparison with clopidogrel, the investigators hypothesize a more pronounced MP levels reduction as a possible mechanism for ticagrelor clinical benefits. Moreover, on the basis of the last evidences of microRNA involvement in the ACS pathophysiology, the investigators aim to assess the effect of ticagrelor on microRNA expression, in order to provide evidences for pleiotropic actions of this drug, which could partially explain its major efficacy in reduction of cardiovascular events in ACS patients.

In summary, principal hypothesis of the study are:

  • Considering that ticagrelor is a stronger P2Y12 receptor inhibitor than clopidogrel, the investigators suppose that an increased inhibition of P2Y12 receptor by ticagrelor could reduce circulating levels of platelet and endothelial MP.
  • In consideration of the observed role of microRNAs in expression of P2Y12 receptor, the investigators speculate that patient's susceptibility to P2Y12 receptor inhibitors could be influenced by microRNAs levels. Moreover, the investigators suppose that ticagrelor could influence microRNAs levels, considered as marker of cardiovascular risk

Aims of the study are:

  • to assess MP levels variation in Non ST-Elevation Acute Coronary Syndromes (NSTE-ACS) patients treated with ticagrelor in addition to low or high acetyl-salicylic acid (ASA), in comparison with clopidogrel+ASA treatment, to demonstrate that major clinical efficacy of ticagrelor could be partially attributed to its influence on release of MP, that have an important role in coronary instability.
  • to evaluate microRNAs levels variation in Non ST-Elevation Acute Coronary Syndromes (NSTE-ACS) patients treated with ticagrelor in addition to low or high ASA, in comparison with clopidogrel+ASA treatment, and to study possible correlations between microRNAs and MP levels, supposing that the ability of ticagrelor in reduced MP level could be related with microRNAs expression.
  Eligibility

Ages Eligible for Study:   50 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • NSTE-ACS
  • Male, 50-80 years old
  • Female, postmenopausal age

Exclusion Criteria:

  • Female, premenopausal age
  • autoimmune disease
  • infectious disease
  • neoplasms
  • diabetes
  • chronic renal failure
  • moderate or severe liver insufficiency
  • GRACE risk score>140
  • ACS or cerebrovascula accidents in previous three months
  • in-stent restenosis
  • surgery or trauma in previous three months
  • active bleeding
  • fibrinolytic therapy within 24 hours before randomization
  • need for oral anticoagulation therapy
  • an increased risk of bradycardia
  • drugs study hypersensitivity (including aspirin)
  • co-administration of ticagrelor or clopidogrel with strong CYP3A4 inhibitors
  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: NCT02071966

Contacts
Contact: Luigi M Biasucci, MD 0630156522

Locations
Italy
Policlinico "A.Gemelli" Recruiting
Rome, Italy, 00168
Contact: LM Biasucci    0630156522      
Principal Investigator: Luigi M Biasucci, Professor         
Sponsors and Collaborators
Catholic University of the Sacred Heart
Investigators
Principal Investigator: Luigi M Biasucci, Professor Catholic University of the Sacred Heart
  More Information

No publications provided

Responsible Party: L.M. Biasucci, Professor, Catholic University of the Sacred Heart
ClinicalTrials.gov Identifier: NCT02071966     History of Changes
Other Study ID Numbers: D5130L00028
Study First Received: February 21, 2014
Last Updated: February 25, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by Catholic University of the Sacred Heart:
Micro-RNA, Microparticles, Ticagrelor, NSTE-ACS

Additional relevant MeSH terms:
Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Clopidogrel
Ticagrelor
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 26, 2014