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)

• Status: Completed
• Trial end date: 2015-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a single-center, prospective, randomized, single-blind, investigator initiated, pharmacokinetic/pharmacodynamic study of parallel design.Patients with ST elevation myocardial infarction (symptom onset<12 hours), undergoing primary percutaneous coronary intervention, who are P2Y12 inhibitor naïve, will be randomized after informed consent, immediately after diagnostic coronary angiography, in a 1:1 ratio to either:

• Ticagrelor 180mg loading dose, in the form of 2 whole tablets administered per os in the supine position (standard administration)

• Ticagrelor 180mg loading dose, in the form of 2 tablets crushed and dispersed in purified water and administered per os with 1-minute-stay in a 60-70 degrees semi-upright sitting position Platelet reactivity assessment will be performed at randomization (Hour 0) and at 0.5, 1, 2, 4 and 6 hours after randomization, using the VerifyNow assay, in platelet reactivity units (PRU). The cutoff >208 PRU will be used for definition of high platelet reactivity (HPR). All platelet reactivity assessments will be performed by a physician blind to the actual treatment given. Additional blood samples will be collected at the same time points for pharmacokinetic analysis. These samples will be collected in vacuum tubes with lithium heparin and will be kept in ice until centrifugation (3000 rpm at 4°C for 10 min, within 30 min of sampling). The resultant plasma will be transferred into a plain polypropylene tube (screw cap) and stored at or below -20°C until analysed.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Patras
• Treatments: Ticagrelor

Criteria

Inclusion Criteria:

1. Age ≥18 years old

2. Patients with STEMI (onset of pain<12 hours) with indication for primary PCI

3. 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