Clinical trial NCT01575795: Standard (180mg) Versus Double (360mg) Loading Dose of Ticagrelor in Patients With ST-elevation Myocardial Infarction (STEMI), Undergoing Primary Percutaneous Coronary Intervention (PCI)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: ST-elevation Myocardial Infarction
Keywords: Ticagrelor
ST elevation acute myocardial infarction
Platelet reactivity
Lead sponsor: University of Patras
Sponsor class: OTHER
First posted: 2012-04-11
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: platelet reactivity at 1 hour post randomization in Group A, between the 2 treatment arms.
timeFrame: 1 hour
Secondary outcomes:
measure: 1. Platelet reactivity at 1 hour post randomization in Group B, between the 2 treatment arms.
timeFrame: 1 hour
measure: 2. Platelet reactivity at 0.5 hour post randomization between the 2 treatment arms separately for Group A and B
timeFrame: 0.5 hour
measure: Platelet reactivity at 2 hours post randomization between the 2 treatment arms separately for Group A and B
timeFrame: 2 hours
measure: Platelet reactivity at 4 hours post randomization between the 2 treatment arms separately for Group A and B
timeFrame: 4 hours
measure: 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
timeFrame: 0.5 hour
measure: 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
timeFrame: 1 hour
measure: 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
timeFrame: 2 hours
measure: 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
timeFrame: 4 hours
measure: Occurrence of any 5-day bleeding event (BARC Types 1-5)
timeFrame: 5 days
measure: Occurrence of 5-day MACEs
timeFrame: 5 days
Other outcomes:
Locations:
city: Rio
country: Greece
facility: Cardiology Department Patras University Hospital
state: Achaia
Study officials:
affiliation: University Hospital of Patras
name: Dimitrios Alexopoulos, MD
role: PRINCIPAL_INVESTIGATOR
References: