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

ST-elevation Myocardial Infarction Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01575795
• Other study ID #: PATRASCARDIOLOGY-10
• Status: Completed
• Phase: Phase 4
• First received: April 9, 2012
• Last updated: April 9, 2013
• Start date: April 2012
• Est. completion date: February 2013

Study information

• Verified date: April 2013
• Source: University of Patras
• Contact: n/a
• Is FDA regulated: No
• Health authority: Greece: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 95 Years

Eligibility

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 < ???? 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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• ST-elevation Myocardial Infarction

Intervention

Drug:
• Ticagrelor
Ticagrelor 360mg loading dose immediately pre prior percutaneous coronary intervention 360mg loading dose
• Ticagrelor
Ticagrelor 180mg loading dose 180mg loading dose

Locations

Country	Name	City	State
Greece	Cardiology Department Patras University Hospital	Rio	Achaia

Sponsors (1)

Lead Sponsor	Collaborator
University of Patras

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	platelet reactivity at 1 hour post randomization in Group A, between the 2 treatment arms.	platelet reactivity at 1 hour post randomization in Group A, between the 2 treatment arms.	1 hour	No
Secondary	1. Platelet reactivity at 1 hour post randomization in Group B, between the 2 treatment arms.	1. Platelet reactivity at 1 hour post randomization in Group B, between the 2 treatment arms.	1 hour	No
Secondary	2. Platelet reactivity at 0.5 hour post randomization between the 2 treatment arms separately for Group A and B	Platelet reactivity at 0.5 hour post randomization between the 2 treatment arms separately for Group A and B	0.5 hour	No
Secondary	Platelet reactivity at 2 hours 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	2 hours	No
Secondary	Platelet reactivity at 4 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	4 hours	No
Secondary	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	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	0.5 hour	No
Secondary	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 1 hour post randomization between the 2 treatment arms, separately for Group A and B	1 hour	No
Secondary	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 2 hours post randomization between the 2 treatment arms, separately for Group A and B	2 hours	No
Secondary	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	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	4 hours	No
Secondary	Occurrence of any 5-day bleeding event (BARC Types 1-5)	Occurrence of any 5-day bleeding event (BARC Types 1-5)	5 days	Yes
Secondary	Occurrence of 5-day MACEs	Occurrence of 5-day MACEs	5 days	Yes