InfarctionHARMONICNCT02690454
Which Platelet Function Test Best Reflects the In Vivo Plasma Concentrations of Ticagrelor and Its Active Metabolite?
An observational study of Infarction and Myocardial Infarction, run by Collegium Medicum w Bydgoszczy at 1 site in Poland.
Trial summary
Ticagrelor is a direct-acting, reversible platelet P2Y12 receptor inhibitor recommended by the recent European Society of Cardiology guidelines in patients with acute coronary syndromes (ACS) (class of recommendation I, level of evidence B). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Infarction, Myocardial Infarction, Cardiovascular Diseases
- How many people
- 45 participants
- Where
- 1 sitePoland
- Study dates
- Nov 2015to Mar 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with myocardial infarction
Who may be able to join
- provision of informed consent prior to any study specific procedures
- diagnosis of acute ST-segment elevation myocardial infarction or acute non-ST-segment
- male or non-pregnant female, aged 18-80 years old
- provision of informed consent for angiography and PCI
Who cannot join
- 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)
Show all 21Show fewer
- history of coagulation disorders
- platelet count less than <100 x10^3/mcl
- hemoglobin concentration less than 10.0 g/dl
- history of moderate or severe hepatic impairment
- history of major surgery or severe trauma (within 3 months)
- patients considered by the investigator to be at risk of bradycardic events
- second or third degree atrioventricular block during screening for eligibility
- history of asthma or severe chronic obstructive pulmonary disease
- patient required dialysis
- manifest infection or inflammatory state
- Killip class III or IV during screening for eligibility
- respiratory failure
- history of severe chronic heart failure (NYHA class III or IV)
- concomitant therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir) or strong CYP3A inducers (rifampicin, phenytoin, carbamazepine, dexamethasone, phenobarbital) within 14 days and during study treatment
- body weight below 50 kg
Trial locations and contacts
1 site in 1 country.
Poland1 site
Cardiology Department, Dr. A. Jurasz University Hospital
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-094
About this study
Official title: Which Platelet Function Test Provides the Best Reflection of the in Vivo Plasma Concentrations of Ticagrelor and Its Active Metabolite? A Pharmacokinetic and Pharmacodynamic Study Including Patients With Myocardial Infarction.
Ticagrelor is a direct-acting, reversible platelet P2Y12 receptor inhibitor recommended by the recent European Society of Cardiology guidelines in patients with acute coronary syndromes (ACS) (class of recommendation I, level of evidence B). Ticagrelor inhibits platelet function stronger, faster and more consistently than clopidogrel, the former standard of antiplatelet therapy. In the landmark PLATO trial (Study of PLATelet inhibition and patient Outcomes), ticagrelor therapy as compared with clopidogrel treatment was associated with the reduced occurrence of major adverse cardiovascular events and all-cause mortality, but also resulted in a small, but statistically significant, increase in the rate of major bleeding. The optimum choice of antiplatelet treatment, aimed to provide each patient with maximum protection against ischemic events, while minimizing the risk of bleeding complications, is the challenge of contemporary ACS therapy. The tool which may help physicians and facilitate clinical decision making is platelet function testing. According to the guidance of both European and American groups of experts, there are three currently recommended platelet function tests, namely the VerifyNow device, the Multiplate analyzer and the Vasodilator Stimulated Phosphoprotein Phosphorylation (VASP) assay. It needs to be emphasized that none of these three methods is preferred over others. So far there are no studies linking pharmacokinetic analysis of ticagrelor and its active metabolite with comparative evaluation of platelet reactivity. The aim of this trial is to assess the relationship between concentrations of ticagrelor and its active metabolite (AR-C124910XX) and results of all three recommended platelet function tests in patients with myocardial infarction. Patients who receive GP IIb/IIIa receptor inhibitor will be excluded from the primary analysis.
Statistical analysis: The correlation will be assessed using correlation coefficients and intraclass correlation coefficients. while the agreement between the results of the compared platelet function tests will be measured using the Kappa statistic and Bland-Altman analysis.
- Conditions
- Infarction, Myocardial Infarction, Cardiovascular Diseases, Heart Diseases, Ischemia, Myocardial Ischemia
- Keywords
- ticagrelor, ticagrelor active metabolite (AR-C124910XX), platelet function tests, the flow cytometric VASP assay, the VerifyNow® device, the Multiplate® analyzer, pharmacokinetics, pharmacodynamics, Multiplate® ADPtest, VerifyNow® PRUTest™, Platelet VASP/P2Y12 assay
- Medical subject headings
- Infarction, Myocardial Infarction, Cardiovascular Diseases, Heart Diseases, Ischemia, Myocardial Ischemia, Necrosis, Pathologic Processes
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation coefficient between ticagrelor plasma concentration and platelet reactivity measurement [platelet reactivity index (PRI), platelet arbitrary aggregation units/min and P2Y12 Reaction Units (PRU)].
Blood samples will be collected in multiple time points in order to assess correlation coefficients in broad ranges of ticagrelor concentrations and values of platelet reactivity. Platelet reactivity measurements will be made immediately after blood sample collection. Ticagrelor plasma concentration will be assessed at the end of participant enrollment. From each study participant, 8 correlation coefficients (for eight sampling points) for each compared methods of platelet reactivity measurement will be included in the final analysis. Values of correlation coefficients will be compared among assessed methods of platelet reactivity measurement.
Platelet reactivity measurements: platelet reactivity index (PRI) assessed by VASP/P2Y12 assay, platelet arbitrary aggregation units/min assessed by Multiple Electrode Aggregometry (Multiplate® ADPtest) and P2Y12 Reaction Units (PRU) assessed by VerifyNow® PRUTest™.
Measured: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Secondary outcomes (8)
Correlation coefficient between ticagrelor active metabolite (AR-C124910XX) plasma concentration and platelet reactivity measurement [platelet reactivity index (PRI), platelet arbitrary aggregation units/min and P2Y12 Reaction Units (PRU)].
Blood samples will be collected in multiple time points in order to assess correlation coefficients in broad ranges of AR-C124910XX concentrations and values of platelet reactivity. Platelet reactivity measurements will be made immediately after blood sample collection. Active ticagrelor metabolite plasma concentration will be assessed at the end of participant enrollment. From each study participant, 8 correlation coefficients (for eight sampling points) for each compared methods of platelet reactivity measurement will be included in the final analysis. Values of correlation coefficients will be compared among assessed methods of platelet reactivity measurement at the end of participant enrollment.
Platelet reactivity measurements: platelet reactivity index (PRI) assessed by VASP/P2Y12 assay, platelet arbitrary aggregation units/min assessed by Multiple Electrode Aggregometry (Multiplate® ADPtest) and P2Y12 Reaction Units (PRU) assessed by VerifyNow® PRUTest™.
Measured: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Correlation coefficient between ticagrelor plasma concentration and inhibition of platelet reactivity assessed with VASP assay, Multiplate® analyzer and VerifyNow® device).
Blood samples will be collected in multiple time points in order to assess correlation coefficients in broad ranges of ticagrelor concentrations and values of inhibition of platelet reactivity. From each study participant, 7 correlation coefficients (for inhibition of platelet reactivity 1, 2, 3, 4, 6, 12, 24 hours post dose) for each compared methods of platelet reactivity measurement will be included in the final analysis. Values of correlation coefficients will be calculated and compared among assessed methods of platelet reactivity measurement at the end of participant enrollment.
Inhibition of platelet aggregation: predose platelet reactivity minus actual platelet reactivity divided by predose platelet reactivity.
Platelet reactivity measurements: platelet reactivity index (PRI) assessed by VASP/P2Y12 assay, platelet arbitrary aggregation units/min assessed by Multiple Electrode Aggregometry (Multiplate® ADPtest) and P2Y12 Reaction Units (PRU) assessed by VerifyNow® PRUTest™.
Measured: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Correlation coefficient between ticagrelor active metabolite (AR-C124910XX) plasma concentration and inhibition of platelet reactivity assessed with VASP assay, Multiplate® analyzer and VerifyNow® device.
Blood samples will be collected in multiple time points in order to assess correlation coefficients in broad ranges of AR-C124910XX concentrations and values of inhibition of platelet reactivity. From each study participant, 7 correlation coefficients (for inhibition of platelet reactivity 1, 2, 3, 4, 6, 12, 24 hours post dose) for each compared methods of platelet reactivity measurement will be included in the final analysis. Values of correlation coefficients will be calculated and compared among assessed methods of platelet reactivity measurement at the end of participant enrollment.
Inhibition of platelet aggregation: predose platelet reactivity minus actual platelet reactivity divided by predose platelet reactivity.
Platelet reactivity measurements: platelet reactivity index (PRI) assessed by VASP/P2Y12 assay, platelet arbitrary aggregation units/min assessed by Multiple Electrode Aggregometry (Multiplate® ADPtest) and P2Y12 Reaction Units (PRU) assessed by VerifyNow® PRUTest™.
Measured: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Kappa statistics assessing agreement between the platelet reactivity measurements performed with the VASP assay and the Multiplate® and VerifyNow® assays in terms of identification of patients with high on-ticagrelor platelet reactivity.
Blood samples will be collected in multiple time points in order to assess a broad range of platelet reactivity values. From each study participant, eight measurements of platelet reactivity (for all sampling points) for each compared methods will be included in the final analysis.The Kappa statistics values will be calculated at the end of participant enrollment.
Measured: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Kappa statistics assessing agreement between the platelet reactivity measurements performed with the Multiplate® assay and the VASP and VerifyNow® assays in terms of identification of patients with low on-ticagrelor platelet reactivity.
Blood samples will be collected collected in multiple time points in order to assess a broad range of platelet reactivity values. From each study participant, eight measurements of platelet reactivity (for all sampling points) for each compared methods will be included in the final analysis.The Kappa statistics values will be calculated at the end of participant enrollment.
Measured: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Correlation coefficient between the standardized values of platelet reactivity performed with the Multiplate® assay and the VASP and VerifyNow® assays.
Blood samples will be collected in multiple time points in order to assess a broad range of platelet reactivity values. From each study participant, eight measurements of platelet reactivity (for all sampling points) for each compared methods will be included in the final analysis. Values of correlation coefficients will be calculated and compared among assessed methods of platelet reactivity measurement at the end of participant enrollment.
Standardized platelet reactivity: actual platelet reactivity minus mean platelet reactivity divided by standardized deviation of the platelet reactivity.
Measured: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Intraclass correlation coefficient between the standardized values of platelet reactivity performed with the Multiplate® assay and the VASP and VerifyNow® assays.
Blood samples will be collected in multiple time points in order to assess a broad range of platelet reactivity values. From each study participant, eight measurements of platelet reactivity (for all sampling points) for each compared methods will be included in the final analysis. Values of intraclass correlation coefficients will be calculated and compared among assessed methods of platelet reactivity measurement at the end of participant enrollment.
Standardized platelet reactivity: actual platelet reactivity minus mean platelet reactivity divided by standardized deviation of the platelet reactivity.
Measured: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Blant-Altman analysis assessing agreement between the standardized values of platelet reactivity performed with the Multiplate® assay and the VASP and VerifyNow® assays.
Blood samples will be collected in multiple time points in order to assess a broad range of platelet reactivity values. From each study participant, eight measurements of platelet reactivity (for all sampling points) for each compared methods will be included in the final analysis. Bland-Altman analysis will be performed at the end of participant enrollment.
Standardized platelet reactivity: actual platelet reactivity minus mean platelet reactivity divided by standardized deviation of the platelet reactivity.
Measured: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2016 (estimated)
- Study startNov 2015
- Primary completionMar 2016
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfarctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Collegium Medicum w Bydgoszczy
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marek Kozinski, Collegium Medicum w Bydgoszczy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02690454
- Sponsor's protocol ID
- CMUMK202E
- Acronym
- HARMONIC
- Status last verified
- Aug 2016
- First submitted
- 26 Nov 2015
- Last updated
- 17 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Which Platelet Function Test Provides the Best Reflection of the in Vivo Plasma Concentrations of Ticagrelor and Its Active Metabolite? A Pharmacokinetic and Pharmacodynamic Study Including Patients With Myocardial Infarction.
- ClinicalTrials.gov ID
- NCT02690454
- Acronym / sponsor ID
- HARMONIC / CMUMK202E
- Conditions
- Infarction, Myocardial Infarction, Cardiovascular Diseases, Heart Diseases, Ischemia, Myocardial Ischemia
- Keywords
- ticagrelor, ticagrelor active metabolite (AR-C124910XX), platelet function tests, the flow cytometric VASP assay, the VerifyNow® device, the Multiplate® analyzer, pharmacokinetics, pharmacodynamics
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Collegium Medicum w BydgoszczyUniversity, hospital or other
- Study start
- Nov 2015
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 24 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ticagrelor is a direct-acting, reversible platelet P2Y12 receptor inhibitor recommended by the recent European Society of Cardiology guidelines in patients with acute coronary syndromes (ACS) (class of recommendation I, level of evidence B). Ticagrelor inhibits platelet function stronger, faster and more consistently than clopidogrel, the former standard of antiplatelet therapy. In the landmark PLATO trial (Study of PLATelet inhibition and patient Outcomes), ticagrelor therapy as compared with clopidogrel treatment was associated with the reduced occurrence of major adverse cardiovascular events and all-cause mortality, but also resulted in a small, but statistically significant, increase in the rate of major bleeding. The optimum choice of antiplatelet treatment, aimed to provide each patient with maximum protection against ischemic events, while minimizing the risk of bleeding complications, is the challenge of contemporary ACS therapy. The tool which may help physicians and facilitate clinical decision making is platelet function testing. According to the guidance of both European and American groups of experts, there are three currently recommended platelet function tests, namely the VerifyNow device, the Multiplate analyzer and the Vasodilator Stimulated Phosphoprotein Phosphorylation (VASP) assay. It needs to be emphasized that none of these three methods is preferred over others. So far there are no studies linking pharmacokinetic analysis of ticagrelor and its active metabolite with comparative evaluation of platelet reactivity. The aim of this trial is to assess the relationship between concentrations of ticagrelor and its active metabolite (AR-C124910XX) and results of all three recommended platelet function tests in patients with myocardial infarction. Patients who receive GP IIb/IIIa receptor inhibitor will be excluded from the primary analysis.
Statistical analysis: The correlation will be assessed using correlation coefficients and intraclass correlation coefficients. while the agreement between the results of the compared platelet function tests will be measured using the Kappa statistic and Bland-Altman analysis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with myocardial infarction
Key inclusion criteria (4 listed)
- provision of informed consent prior to any study specific procedures
- diagnosis of acute ST-segment elevation myocardial infarction or acute non-ST-segment
- male or non-pregnant female, aged 18-80 years old
- provision of informed consent for angiography and PCI
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Correlation coefficient between ticagrelor plasma concentration and platelet reactivity measurement [platelet reactivity index (PRI), platelet arbitrary aggregation units/min and P2Y12 Reaction Units (PRU)].
Time frame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Blood samples will be collected in multiple time points in order to assess correlation coefficients in broad ranges of ticagrelor concentrations and values of platelet reactivity. Platelet reactivity measurements will be made immediately after blood sample collection. Ticagrelor plasma concentration will be assessed at the end of participant enrollment. From each study participant, 8 correlation coefficients (for eight sampling points) for each compared methods of platelet reactivity measurement will be included in the final analysis. Values of correlation coefficients will be compared among assessed methods of platelet reactivity measurement. Platelet reactivity measurements: platelet reactivity index (PRI) assessed by VASP/P2Y12 assay, platelet arbitrary aggregation units/min assessed by Multiple Electrode Aggregometry (Multiplate® ADPtest) and P2Y12 Reaction Units (PRU) assessed by VerifyNow® PRUTest™.
8 secondary outcomes
Correlation coefficient between ticagrelor active metabolite (AR-C124910XX) plasma concentration and platelet reactivity measurement [platelet reactivity index (PRI), platelet arbitrary aggregation units/min and P2Y12 Reaction Units (PRU)].
Time frame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Correlation coefficient between ticagrelor plasma concentration and inhibition of platelet reactivity assessed with VASP assay, Multiplate® analyzer and VerifyNow® device).
Time frame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Correlation coefficient between ticagrelor active metabolite (AR-C124910XX) plasma concentration and inhibition of platelet reactivity assessed with VASP assay, Multiplate® analyzer and VerifyNow® device.
Time frame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Kappa statistics assessing agreement between the platelet reactivity measurements performed with the VASP assay and the Multiplate® and VerifyNow® assays in terms of identification of patients with high on-ticagrelor platelet reactivity.
Time frame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Kappa statistics assessing agreement between the platelet reactivity measurements performed with the Multiplate® assay and the VASP and VerifyNow® assays in terms of identification of patients with low on-ticagrelor platelet reactivity.
Time frame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Correlation coefficient between the standardized values of platelet reactivity performed with the Multiplate® assay and the VASP and VerifyNow® assays.
Time frame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Intraclass correlation coefficient between the standardized values of platelet reactivity performed with the Multiplate® assay and the VASP and VerifyNow® assays.
Time frame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Blant-Altman analysis assessing agreement between the standardized values of platelet reactivity performed with the Multiplate® assay and the VASP and VerifyNow® assays.
Time frame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Infarction and Myocardial Infarction, run by Collegium Medicum w Bydgoszczy at 1 site in Poland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation coefficient between ticagrelor plasma concentration and platelet reactivity measurement [platelet reactivity index (PRI), platelet arbitrary aggregation units/min and P2Y12 Reaction Units (PRU)]. (time frame: predose, 1, 2, 3, 4, 6, 12, 24 hours post-dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2016.