OraL Crushed and dIspersed Ticagrelor 180mg Compared to Whole Tablets of eQUal Dose in STEMI Patients unDergoing Primary PCI: a Pharmacokinetic/Pharmacodynamic Study (the LIQUID Study)

Preparation of Ticagrelor liquid formulation:

Crushed and dispersed Ticagrelor 180mg for oral administration will be prepared as follows: two ticagrelor 90mg tablets are placed in a mortar and crushed for 60 s using a pestle. 20 mL of purified water will be added in the mortar and stirred for 60s. The liquid is transferred to a dosing cup and another 15 mL of purified water is added to the mortar and stirred, ensuring that all powder has been dispersed and none remained on the mortar and pestle. Again the liquid is transferred to the dosing cup. The same procedure is repeated with 15 ml of purified water.The total contents are stirred for another 30 s to ensure that all remaining tablet particles are dispersed.

Inclusion criteria

• Age ≥18 years old
• Patients with STEMI (onset of pain<12 hours) with indication for primary PCI
• Informed consent obtained in writing

Exclusion criteria

Pregnancy/Breastfeeding

• Severe nausea or vomiting
• Treatment with a P2Y12 inhibitor within the previous 1 month
• Inability to give informed consent
• Hemodynamic instability
• Arrhythmias requiring cardioversion, temporary pacemaker insertion or intravenous antiarrhythmic agents
• Killip class ≥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
• Thombocytopenia (<100.000 / μL) at randomization
• Anaemia (Hct <30%) at randomization
• Polycytaemia (Hct > 52%) at randomization
• Periprocedural IIb/IIIa inhibitor administration
• Thrombolysis administration
• Recent (< 6 weeks) major surgery or trauma, including GABG.
• 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).
• Patients considered by the investigator to be at increased risk of bradycardiac events.
• Dialysis required.
• Severe uncontrolled chronic obstructive pulmonary disease
• Known severe hepatic impairement