Standard (180mg) Versus Double (360mg) Loading Dose of Ticagrelor in Patients With ST-elevation Myocardial Infarction (STEMI), Undergoing Primary Percutaneous Coronary Intervention (PCI)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dimitrios Alexopoulos, University of Patras
ClinicalTrials.gov Identifier:
NCT01575795
First received: April 9, 2012
Last updated: April 9, 2013
Last verified: April 2013
  Purpose

This is a multi-center, prospective, randomized, single-blind, investigator initiated, pharmacodynamic study of parallel design, performed at 3 institutions (Patras University Hospital; Evangelismos Athens General Hospital; Gennimatas Athens General Hospital).

Patients with ST elevation myocardial infarction (symptom onset < 12 hours), undergoing primary percutaneous coronary intervention, who are antiplatelet naïve (Group A) or present high residual PR (defined as PRU ≥ 208) immediately before primary percutaneous coronary intervention, will be randomized after informed consent, in a 1:1 ratio to either:

Ticagrelor 180mg loading dose (LD), followed by a 90mg x2 maintenance dose (MD )starting 12±6 hours post LD Or Ticagrelor 360mg loading dose (LD), followed by a 90mg x2 maintenance dose (MD) starting 12±6 hours post LD Platelet reactivity assessment will be performed at randomization (Hour 0) and at 0.5, 1, 2, 4 hours after randomization, using the VerifyNow assay, in platelet reactivity units (PRU).

Documentation of major adverse cardiac events (death, myocardial infarction, stroke, urgent revascularization procedure with PCI or CABG) and bleeding (according to Bleeding Academic Research Consortium criteria) will be performed until patient's discharge.


Condition Intervention Phase
ST-elevation Myocardial Infarction
Drug: Ticagrelor
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Standard (180mg) Versus Double (360mg) Loading Dose of Ticagrelor in Patients With ST-elevation Myocardial Infarction (STEMI), Undergoing Primary Percutaneous Coronary Intervention (PCI): a Multi-center Randomized Parallel Pharmacodynamic Study.

Resource links provided by NLM:


Further study details as provided by University of Patras:

Primary Outcome Measures:
  • platelet reactivity at 1 hour post randomization in Group A, between the 2 treatment arms. [ Time Frame: 1 hour ] [ Designated as safety issue: No ]
    platelet reactivity at 1 hour post randomization in Group A, between the 2 treatment arms.


Secondary Outcome Measures:
  • 1. Platelet reactivity at 1 hour post randomization in Group B, between the 2 treatment arms. [ Time Frame: 1 hour ] [ Designated as safety issue: No ]
    1. Platelet reactivity at 1 hour post randomization in Group B, between the 2 treatment arms.

  • 2. Platelet reactivity at 0.5 hour post randomization between the 2 treatment arms separately for Group A and B [ Time Frame: 0.5 hour ] [ Designated as safety issue: No ]
    Platelet reactivity at 0.5 hour post randomization between the 2 treatment arms separately for Group A and B

  • Platelet reactivity at 2 hours post randomization between the 2 treatment arms separately for Group A and B [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
    Platelet reactivity at 2 hours post randomization between the 2 treatment arms separately for Group A and B

  • Platelet reactivity at 4 hours post randomization between the 2 treatment arms separately for Group A and B [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
    Platelet reactivity at 4 hours post randomization between the 2 treatment arms separately for Group A and B

  • 3. High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 0.5 hour post randomization between the 2 treatment arms, separately for Group A and B [ Time Frame: 0.5 hour ] [ Designated as safety issue: No ]
    High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 0.5 hour post randomization between the 2 treatment arms, separately for Group A and B

  • High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 1 hour post randomization between the 2 treatment arms, separately for Group A and B [ Time Frame: 1 hour ] [ Designated as safety issue: No ]
    High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 1 hour post randomization between the 2 treatment arms, separately for Group A and B

  • High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 2 hours post randomization between the 2 treatment arms, separately for Group A and B [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
    High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 2 hours post randomization between the 2 treatment arms, separately for Group A and B

  • High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 4 hours post randomization between the 2 treatment arms, separately for Group A and B [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
    High on treatment platelet reactivity (HTPR) rates (≥208 PRU) at 4 hours post randomization between the 2 treatment arms, separately for Group A and B

  • Occurrence of any 5-day bleeding event (BARC Types 1-5) [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
    Occurrence of any 5-day bleeding event (BARC Types 1-5)

  • Occurrence of 5-day MACEs [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
    Occurrence of 5-day MACEs


Enrollment: 83
Study Start Date: April 2012
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ticagrelor 180mg loading dose
Ticagrelor 180mg loading dose
Drug: Ticagrelor
Ticagrelor 180mg loading dose 180mg loading dose
Experimental: Ticagrelor 360mg loading dose
Ticagrelor 360mg loading dose
Drug: Ticagrelor
Ticagrelor 360mg loading dose immediately pre prior percutaneous coronary intervention 360mg loading dose

  Eligibility

Ages Eligible for Study:   18 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years old
  2. Patients with STEMI (onset of pain < 12 hours) with indication for primary PCI
  3. Antiplatelet naïve or presenting HTPR (≥ 208 PRU) immediately before primary percutaneous coronary intervention
  4. Informed consent obtained in writing

Exclusion Criteria

  • Pregnancy
  • Breastfeeding
  • Inability to give informed consent or high likelihood of being unavailable until the Day 5
  • Cardiogenic shock
  • Major periprocedural complications (death, stent thrombosis, vessel perforation, arrhythmias requiring cardioversion, temporary pacemaker insertion or intravenous antiarrhythmic agents, respiratory failure requiring intubation, vascular injury (arteriovenous shunt, retroperitoneal bleeding), major bleeding (need for bood transfusion or drop in haemoglobin post-PCI by ≥ 5 gr/ dl or intracranial bleeding).
  • Unsuccessful PCI (residual stenosis > 30% or flow < ΤΙΜΙ 3)
  • Known hypersensitivity to ticagrelor
  • History of gastrointestinal bleeding, genitourinary bleeding or other site abnormal bleeding within the previous 3 months.
  • Other bleeding diathesis, or considered by investigator to be at high risk for bleeding
  • Any previous history of stroke, intracranial hemorrhage or disease (neoplasm, arteriovenous malformation, aneurysm).
  • Thrombocytopenia (< 100.000/μL) at randomization
  • Anaemia (Hct < 30%) at randomization
  • Polycytaemia (Hct > 52%) at randomization
  • Periprocedural IIb/IIIa inhibitors administration
  • Thrombolysis administration
  • Recent (< 6 weeks) major surgery or trauma, including GABG.
  • Subjects receiving daily treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors that cannot be discontinued for the duration of the study.
  • Concomitant oral or IV therapy with strong CY P3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazana vir, grapefruit juice N1 L/d), CYP3A substrates with narrow therapeutic indices (cyclosporine, quinidine), or strong CYP3A inducers (rifampin/rifampicin, phenytoin, carbamazepine).
  • Increased risk of bradycardiac events.
  • Dialysis required.
  • Severe uncontrolled chronic obstructive pulmonary disease
  • Known severe hepatic impairment
  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: NCT01575795

Locations
Greece
Cardiology Department Patras University Hospital
Rio, Achaia, Greece, 26500
Sponsors and Collaborators
University of Patras
Investigators
Principal Investigator: Dimitrios Alexopoulos, MD Patras University Hospital
  More Information

No publications provided

Responsible Party: Dimitrios Alexopoulos, Professor, University of Patras
ClinicalTrials.gov Identifier: NCT01575795     History of Changes
Other Study ID Numbers: PATRASCARDIOLOGY-10
Study First Received: April 9, 2012
Last Updated: April 9, 2013
Health Authority: Greece: Ethics Committee

Keywords provided by University of Patras:
Ticagrelor
ST elevation acute myocardial infarction
Platelet reactivity

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Ticagrelor
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 26, 2014