Comparison of Ticagrelor Pharmacokinetics and Pharmacodynamics in STEMI and NSTEMI Patients

Myocardial Infarction Clinical Trial

— PINPOINT  

Official title:

Comparison of Ticagrelor Pharmacokinetics and Pharmacodynamics in ST-elevation Myocardial Infarction and Non-ST-elevation Myocardial Infarction Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02602444
• Other study ID #: CMUMK202B
• Status: Completed
• Phase: N/A
• First received: November 9, 2015
• Last updated: April 26, 2017
• Start date: October 2015
• Est. completion date: January 2017

Study information

• Verified date: April 2017
• Source: Collegium Medicum w Bydgoszczy
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of the PINPOINT study is to compare pharmacokinetics (PK) and pharmacodynamics (PD) of ticagrelor in ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) patients designated to invasive strategy. Data regarding comparison of PK and antiplatelet action of ticagrelor in STEMI and NSTEMI are sparse. Recommended dosing regimens of ticagrelor are identical for both STEMI and NSTEMI, although it is not known whether PK and PD features of ticagrelor are uniform in these patients.

Description:

The European Society of Cardiology and American Heart Association guidelines recommend use of ticagrelor or prasugrel as a treatment of choice in patients with both STEMI and NSTEMI (class of recommendation I, level of evidence B). Recommended dosing regimens of ticagrelor are identical in STEMI and NSTEMI patients, although epidemiology, clinical approach and early outcomes differ between these two types of myocardial infarction. It is not known whether PK and PD features of ticagrelor are uniform in STEMI and NSTEMI patients. However, the existing body of evidence suggest that PK and PD of ticagrelor may be attenuated in STEMI patients compared to healthy subjects and patients with stable coronary artery disease, which may expose STEMI patients at increased risk of developing thrombotic complications secondary to insufficient platelet inhibition. The PINPOINT study could provide a valuable insight into the knowledge regarding ticagrelor action in STEMI vs. NSTEMI patients.

Since there is no reference study comparing pharmacokinetics of ticagrelor in STEMI and NSTEMI patients, we decided to perform an internal pilot study of approximately 30 patients (15 patients with each type of myocardial infarction) for estimating the final sample size.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• provision of informed consent prior to any study specific procedures

• diagnosis of acute ST-segment elevation myocardial infarction or acute non-ST-segment elevation myocardial infarction

• male or non-pregnant female, 18 years old and older

• provision of informed consent for angiography and PCI

Exclusion Criteria:

• treatment with ticlopidine, clopidogrel, prasugrel or ticagrelor within 14 days before the study enrollment

• hypersensitivity to ticagrelor

• current treatment with oral anticoagulant or chronic therapy with low-molecular-weight heparin

• active bleeding

• history of intracranial hemorrhage

• recent gastrointestinal bleeding (within 30 days)

• history of coagulation disorders

• history of moderate or severe hepatic impairment

• history of major surgery or severe trauma (within 3 months)

• second or third degree atrioventricular block during screening for eligibility

• patient required dialysis

• manifest infection or inflammatory state

• Killip class III or IV during screening for eligibility

• respiratory failure

• current therapy with strong CYP3A inhibitors or strong CYP3A inducers

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

Drug:
• ticagrelor
180 mg loading dose

Locations

Country	Name	City	State
Poland	Cardiology Department, Dr. A. Jurasz University Hospital	Bydgoszcz	Kujawsko-pomorskie

Sponsors (1)

Lead Sponsor	Collaborator
Collegium Medicum w Bydgoszczy

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the plasma concentration-time curve for ticagrelor (AUC 0-6h)		prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
Secondary	Area under the plasma concentration-time curve for AR-C124910XX (AUC 0-6h)		prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
Secondary	Area under the plasma concentration-time curve for ticagrelor (AUC 0-12h)		prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
Secondary	Area under the plasma concentration-time curve for AR-C124910XX (AUC 0-12h)		prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
Secondary	Maximum concentration (Cmax) of ticagrelor and AR-C124910XX		12 hours
Secondary	Time to maximum concentration (Cmax) for ticagrelor and AR-C124910XX		12 hours
Secondary	Platelet reactivity index (PRI) assessed by VASP assay		prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
Secondary	Platelet reactivity assessed by Multiple Electrode Aggregometry	It will be assessed in all predefined time points in all study participants except those treated with GP IIb/IIIa receptor inhibitors.	prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h, 12h post dose
Secondary	Percentage of patients with high platelet reactivity (HPR) after the loading dose of ticagrelor assessed with VASP and Multiple Electrode Aggregometry		2 hours
Secondary	Time to reach platelet reactivity below the cut-off value for HPR evaluated with VASP and Multiple Electrode Aggregometry		12 hours