Sampling P2Y12 Receptor Inhibition With Prasugrel and Ticagrelor in Patients Submitted to Thrombolysis (SAMPA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Federal University of São Paulo
Sponsor:
Information provided by (Responsible Party):
Leonardo de Freitas Campos Guimarães, Federal University of São Paulo
ClinicalTrials.gov Identifier:
NCT02215993
First received: June 3, 2014
Last updated: August 27, 2014
Last verified: August 2014
  Purpose

Introduction:

Platelet aggregation plays an important role in ischemic complications in patients undergoing to percutaneous coronary intervention (PCI). The addition of clopidogrel, as a second antiplatelet agent, to acetylsalicylic acid (ASA) was effective in reducing major cardiovascular events in patients with acute coronary syndrome (ACS).

However, approximately 30% of ACS patients are resistant to clopidogrel, representing a population of medically vulnerable and high risk for major cardiovascular events, including myocardial infarction (MI), stent thrombosis and death.

In the randomized trial TRITON, prasugrel compared to clopidogrel was more effective in significantly reducing the rates of MI (7.4% vs. 9.4%) and stent thrombosis (2.4% vs .1,1%) in patients with ACS, however, patients treated with prasugrel showed higher rates of bleeding (2.4 vs. 1.8%) and no difference in mortality. Upon analysis of subgroups is not recommended its use in patients with a history of stroke in those older than 75 years and weighing less than 60 kg.

The latest class of inhibitors of the P2Y12 receptor is the cyclopentyl-triazolopyrimidines represented by ticagrelor. Unlike the thienopyridines, ticagrelor interacts with the platelet receptors in a reversible way and has a beginning and peak of action faster.

The efficacy and safety of ticagrelor were evaluated in the study PLATO, where 18.624 patients with ACS were randomized to receive clopidogrel (75mg/day, with a loading dose of 300 to 600mg) or ticagrelor (90mg 2x/day with a loading dose of 180mg) The primary combined endpoint (mortality from vascular causes, MI or stroke) at 12 months was significantly lower in the ticagrelor (9.8% vs. 11.7%). There was no significant difference in the rates of major bleeding in both groups. Moreover, the isolated analysis of the rates of MI, vascular mortality and mortality from all causes showed statistically significant reduction in the ticagrelor users. In this study, the main adverse effects were dyspnea and bradycardia.

The assessment of platelet reactivity may allow the individualization of antiplatelet therapy. However, simply increasing the dose of clopidogrel in patients who persisted with high platelet reactivity was not able to reduce the combined endpoint of cardiovascular death, nonfatal myocardial infarction and stent thrombosis in six months.

In a population of patients with stable coronary artery disease, the substitution of clopidogrel for ticagrelor showed a rapid and persistent decrease in platelet aggregation measured by different laboratory methods. However, in patients with ACS subjected to PCI, the assessment of platelet aggregation after the replacement of clopidogrel for prasugrel or ticagrelor still requires evidence.

Objectives:

To evaluate the platelet response to ticagrelor and prasugrel in ACS patients with ST-segment elevation submitted to thrombolysis.

To evaluate security in follow up of 30 days.

Methods:

The study will be a prospective, randomized, single-center (São Paulo Hospital - Federal University of São Paulo), single-blind. The investigators will select 50 patients admitted with ACS with ST-segment elevation submitted to thrombolysis and who underwent cardiac catheterization between 3 to 24 hours in the case of reperfusion or immediately for rescue angioplasty. Blood sample for analysis of platelet aggregation through the system VerifyNow ®, shall be obtained immediately after the procedure on patients on clopidogrel for at least seven days in maintenance dose of 75mg or after 8 to 6 hours after the dose of 300mg and 600mg respectively. Patients will be randomized in a 1:1 ratio to receive ticagrelor the dose of 180mg and maintained dose of 90 mg twice a day for thirty days or prasugrel dose of 60mg and maintained for thirty days at a daily dose of 10mg. A new blood sample and analysis of platelet aggregation will be repeated after 2, 6 and 24 hours. The demographic and clinical data of this population will be collected in specific form and stored in databases for later analysis


Condition Intervention Phase
Acute Coronary Syndrome
Platelet Function
Drug: Prasugrel
Drug: Ticagrelor
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Sampling P2Y12 Receptor Inhibition With Prasugrel and Ticagrelor in Patients Submitted to Thrombolysis After Loading Dose of Clopidogrel

Resource links provided by NLM:


Further study details as provided by Federal University of São Paulo:

Primary Outcome Measures:
  • Assessment of change in platelet aggregation [ Time Frame: time 0, 2, 6 and 24 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The number of incidence of bleeding [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: July 2013
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Prasugrel
After 300mg or 600mg loading dose of clopidogrel, this medication will be replaced by 60 mg prasugrel followed by 10mg per day for 30 days.
Drug: Prasugrel
After 8 to 6 hours after the dose of 300mg and 600mg respectively. Patients will be randomized in a 1:1 ratio to receive ticagrelor the dose of 180mg and maintained dose of 90 mg twice a day for thirty days or prasugrel dose of 60mg and maintained for thirty days at a daily dose of 10mg.
Active Comparator: Ticagrelor
After 300mg or 600mg loading dose of clopidogrel, this medication will be replaced by 180 mg ticagrelor followed by 90mg twice a day for 30 days.
Drug: Ticagrelor
After 8 to 6 hours after the dose of 300mg and 600mg respectively. Patients will be randomized in a 1:1 ratio to receive ticagrelor the dose of 180mg and maintained dose of 90 mg twice a day for thirty days or prasugrel dose of 60mg and maintained for thirty days at a daily dose of 10mg.

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • less than 75 years
  • sign the consent form
  • Acute coronary syndrome with ST-segment elevation submitted to thrombolysis

Exclusion Criteria:

  • use of IIbIIIa inhibitor
  • less than 60 kg
  • history of stroke
  • Patients with sick sinus syndrome, atrioventricular block second or third degree, not protected by pacemaker
  • Chronic obstructive pulmonary disease
  • Asthma
  • Heart failure class III / IV
  • renal replacement therapy
  • Use of inducers (carbamazepine, phenytoin, phenobarbital, rifampicin and dexamethasone) or inhibitors (ketoconazole, itraconazole, ritonavir, saquinavir, clarithromycin) potent enzyme PYP3A
  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: NCT02215993

Contacts
Contact: Leonardo Guimaraes +5511975498500 leofcguima@gmail.com
Contact: Adriano Caixeta +5511952362000 acaixeta@me.com

Locations
Brazil
Federal University of São Paulo Recruiting
São Paulo, Brazil, 04024-002
Contact: Adriano Caixeta    +551155764014    acaixeta@me.com   
Contact: Leonardo Guimaraes    +551155754016    leofcguima@gmail.com   
Principal Investigator: Leonardo Guimaraes         
Sponsors and Collaborators
Federal University of São Paulo
Investigators
Principal Investigator: Leonardo Guimaraes Federal University of São Paulo
Study Director: Adriano Caixeta Federal University of São Paulo
  More Information

No publications provided

Responsible Party: Leonardo de Freitas Campos Guimarães, PhD student, Federal University of São Paulo
ClinicalTrials.gov Identifier: NCT02215993     History of Changes
Other Study ID Numbers: 51476
Study First Received: June 3, 2014
Last Updated: August 27, 2014
Health Authority: Brazil: Ethics Committee

Keywords provided by Federal University of São Paulo:
Ticagrelor
Prasugrel
VerifyNow
Acute coronary syndrome

Additional relevant MeSH terms:
Syndrome
Acute Coronary Syndrome
Disease
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Clopidogrel
Ticagrelor
Prasugrel
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 September 18, 2014