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)

NCT02046486 | Completed Phase 4

• 1 other identifier: LIQUID study
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

ST Elevation Myocardial Infarction

Keywords

ticagrelor; ST elevation myocardial infarction; liquid formulation

Outcome Measures

Primary Outcomes (2)

• Ticagrelor's Cmax over 1 hour post ticagrelor administration

  1 hour

• Area under the ticagrelor plasma concentration versus time curve (AUC0-1) over 1 hour post ticagrelor administration

  1 hour

Secondary Outcomes (12)

• Platelet reactivity at 1 hour post randomization

  1 hour

• HPR rate at 1 hour post randomization

  1 hour

• Platelet reactivity at 2 hours post randomization

  2 hours

• HPR rate at 2 hours post randomization

  2 hours

• AR-C124910XX Cmax over 1 hour post ticagrelor administration

  1 hour

Study Arms (2)

Ticagrelor 180mg whole tablets

ACTIVE COMPARATOR

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

Drug: Ticagrelor 180mg whole tablets

Ticagrelor 180mg crushed and dispersed

EXPERIMENTAL

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

Drug: Ticagrelor 180mg crushed and dispersed

Interventions

Ticagrelor 180mg whole tablets DRUG

Ticagrelor 180mg whole tablets

Ticagrelor 180mg crushed and dispersed DRUG

Ticagrelor 180mg crushed and dispersed

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Patras: lead

Study Sites (1)

Patras University Hospital Department of Cardiology

Pátrai, Achaia, 26500, Greece

Location

Related Publications (1)

• 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.

  PMID: 26315810 DERIVED

MeSH Terms

Conditions

ST Elevation Myocardial Infarction

Interventions

Ticagrelor

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Cardiology

Study Record Dates

• First Submitted: January 23, 2014
• First Posted: January 27, 2014
• Study Start: January 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: January 27, 2015

Record last verified: 2015-01

Locations

GR (1)