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)

NCT ID: NCT02046486

Last Updated: 2015-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2015-01-31

Brief 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.

Detailed Description

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.

Conditions

ST Elevation Myocardial Infarction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Ticagrelor 180mg whole tablets

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

Group Type: ACTIVE_COMPARATOR

Ticagrelor 180mg whole tablets

Intervention Type: DRUG

Ticagrelor 180mg crushed and dispersed

Ticagrelor 180mg in the form of 2 tablets crushed and dispersed in purified water administered per os with 1-minute-stay in a 60-70 degrees semi-upright sitting position

Group Type: EXPERIMENTAL

Ticagrelor 180mg crushed and dispersed

Intervention Type: DRUG

Interventions

Ticagrelor 180mg whole tablets

Intervention Type: DRUG

Ticagrelor 180mg crushed and dispersed

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Patras

OTHER

Sponsor Role: lead

Responsible Party

Dimitrios Alexopoulos

Professor of Cardiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Patras University Hospital Department of Cardiology

Pátrai, Achaia, Greece

Countries

Greece

References

Alexopoulos D, Barampoutis N, Gkizas V, Vogiatzi C, Tsigkas G, Koutsogiannis N, Davlouros P, Hahalis G, Nylander S, Parodi G, Xanthopoulou I. Crushed Versus Integral Tablets of Ticagrelor in ST-Segment Elevation Myocardial Infarction Patients: A Randomized Pharmacokinetic/Pharmacodynamic Study. Clin Pharmacokinet. 2016 Mar;55(3):359-67. doi: 10.1007/s40262-015-0320-0.

Reference Type: DERIVED

PMID: 26315810 (View on PubMed)

Other Identifiers

LIQUID study

Identifier Type: -

Identifier Source: org_study_id