Ignite Creation Date:
2024-05-06 @ 7:43 AM
Last Modification Date:
2024-10-26 @ 11:51 AM
Study NCT ID:
NCT02587260
Status:
COMPLETED
Last Update Posted:
2017-02-13
First Post:
2015-10-23
Brief Title:
Hunting for the Off-Target Properties of Ticagrelor on Endothelial Function in Humans HI-TECH
Sponsor:
Erasmus Medical Center
Organization:
Erasmus Medical Center
Study Overview
Official Title:
Hunting for the Off-Target Properties of Ticagrelor on Endothelial Function and Other Circulating Biomarkers in Humans
Status:
COMPLETED
Status Verified Date:
2017-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HI-TECH
Brief Summary:
The purpose of this randomized cross-over study is to ascertain if ticagrelor but not prasugrel or clopidogrel is associated to an improved endothelial function as assessed with peripheral arterial tonometry and markers of endothelial function measurement in post-ACS patients
Detailed Description:
Extensive literature documents that endothelial dysfunction is associated with almost every condition predisposing to atherosclerosis and cardiovascular disease Hence endothelial dysfunction is significantly associated with the burden of cardiovascular risk and can be considered a barometer of the total risk burden Importantly microvascular dysfunction has been shown to increase risk of future cardiovascular events
This study aims to clarify if ticagrelor but not prasugrel or clopidogrel is associated to an improved reactive hyperemia index RHI and circulating levels of specific biomarkers of endothelial function at treatment steady state Ticagrelor has previously been demonstrated to increase adenosine levels by inhibiting adenosine reuptake in red blood cells by inhibiting the equilibrative nucleoside transporter ENT-1 Furthermore ticagrelor can induce adenosine triphosphate ATP release from human red blood cells Interestingly ticagrelor but not clopidogrel or prasugrel have been recently shown to be associated to an improved endothelial function as evaluated with peripheral arterial tonometry after forearm ischemia
Post-ACS patients who experienced an acute coronary syndrome and thereby started therapy with an oral P2Y12 inhibitor at least 30 days before will be consecutively screened for possible inclusion Patients will then be randomised to receive in a sequential manner the three oral P2Y12 blockers ie ticagrelor prasugrel or clopidogrel for at least 30 days each according to a balanced cross-over study design including the sequences below
Seq Per PI PII PIII SI T P C SII T C P SIII P T C SIV P C T SV C T P SVI C P T During the three months study period the therapy with the P2Y12 inhibitor will be switched as for randomization sequence scheme
When started each drug will be given with the corresponding loading dose of 600 mg for clopidogrel and then continued at 75 mgday 180 mg for ticagrelor and then continued at 90 mg bid and 60 mg for prasugrel and then continued at 10 mgday 5 mgday for patients 75 years or weighing 60 kg
The main measurements including reactive hypermedia index PRU aspirin reaction units and circulating markers of endothelial function will be performed at baseline after P2Y12-inhibitor loading dose before and after P2Y12-inhibitor maintenance dose
During the visit blood pressure will be measured in the contralateral arm before examination The EndoPAT probes will be placed on the index fingers If the index finger will be missing or deformed another finger will be used using the same finger on both hands Baseline registration will be conducted for 5 min The test arm will be then occluded for 5 min using a standard blood pressure cuff placed on the upper arm Subsequently the cuff was deflated and the registration continued for 5 more minutes After EndoPAT blood will be drawn to collect serum and plasma for biomarkers assessment Asymmetrical dimethylarginine ADMA adenosine plasma concentration von willebrand factor antigen endothelin-1 C-reactive protein soluble fms-like tyrosine kinase-1 sFLT-1 intercellular cell adhesion molecule-1 ICAM-1 vascular cell adhesion molecule-1 VCAM-1 prothrombin fragment 12 fibrinopeptide A and thrombin-antithrombin complex TAT To assess the relationship between residual platelet reactivity or percent inhibition and effect of P2Y12 oral blocker on endothelial function platelet function testing will be also carried out acutely and at treatment steady state by means of the Verifynow system using both P2Y12 and aspirin assays
Based on previous findings we set mean RHI at 18 with a within subjects SD of 031 Hence 36 patients completing all sequences ie 6 ptsequence will provide 90 power to detect a 10 RHI relative change in the ticagrelor group with a two-sided alpha level at 5 To account for drop outs as well as incomplete data assessment at all time points a final sample size of 50 patients will be recruited
Patients will be provided with a regular drug prescription standard of care medication At each follow-up the investigator will collect information about adherence to the study drug and register the charge number of the prescribed P2Y12
Allocation of study treatment will be performed via a web-based interactive randomization system based on a computer-generated random sequence with a random block size stratified according to the type of P2Y12 inhibitor ticagrelor vs prasugrel vs clopidogrel as well as for the presence of diabetes mellitus
Adverse events are defined as any undesirable experience occurring to a subject during the study whether or not considered related to study All adverse events reported spontaneously by the subject or observed by the investigator or his staff will be recorded Serious adverse events in this study are considered to be extremely rare
This study aims to clarify if ticagrelor but not prasugrel or clopidogrel is associated to an improved reactive hyperemia index RHI and circulating levels of specific biomarkers of endothelial function at treatment steady state Ticagrelor has previously been demonstrated to increase adenosine levels by inhibiting adenosine reuptake in red blood cells by inhibiting the equilibrative nucleoside transporter ENT-1 Furthermore ticagrelor can induce adenosine triphosphate ATP release from human red blood cells Interestingly ticagrelor but not clopidogrel or prasugrel have been recently shown to be associated to an improved endothelial function as evaluated with peripheral arterial tonometry after forearm ischemia
Post-ACS patients who experienced an acute coronary syndrome and thereby started therapy with an oral P2Y12 inhibitor at least 30 days before will be consecutively screened for possible inclusion Patients will then be randomised to receive in a sequential manner the three oral P2Y12 blockers ie ticagrelor prasugrel or clopidogrel for at least 30 days each according to a balanced cross-over study design including the sequences below
Seq Per PI PII PIII SI T P C SII T C P SIII P T C SIV P C T SV C T P SVI C P T During the three months study period the therapy with the P2Y12 inhibitor will be switched as for randomization sequence scheme
When started each drug will be given with the corresponding loading dose of 600 mg for clopidogrel and then continued at 75 mgday 180 mg for ticagrelor and then continued at 90 mg bid and 60 mg for prasugrel and then continued at 10 mgday 5 mgday for patients 75 years or weighing 60 kg
The main measurements including reactive hypermedia index PRU aspirin reaction units and circulating markers of endothelial function will be performed at baseline after P2Y12-inhibitor loading dose before and after P2Y12-inhibitor maintenance dose
During the visit blood pressure will be measured in the contralateral arm before examination The EndoPAT probes will be placed on the index fingers If the index finger will be missing or deformed another finger will be used using the same finger on both hands Baseline registration will be conducted for 5 min The test arm will be then occluded for 5 min using a standard blood pressure cuff placed on the upper arm Subsequently the cuff was deflated and the registration continued for 5 more minutes After EndoPAT blood will be drawn to collect serum and plasma for biomarkers assessment Asymmetrical dimethylarginine ADMA adenosine plasma concentration von willebrand factor antigen endothelin-1 C-reactive protein soluble fms-like tyrosine kinase-1 sFLT-1 intercellular cell adhesion molecule-1 ICAM-1 vascular cell adhesion molecule-1 VCAM-1 prothrombin fragment 12 fibrinopeptide A and thrombin-antithrombin complex TAT To assess the relationship between residual platelet reactivity or percent inhibition and effect of P2Y12 oral blocker on endothelial function platelet function testing will be also carried out acutely and at treatment steady state by means of the Verifynow system using both P2Y12 and aspirin assays
Based on previous findings we set mean RHI at 18 with a within subjects SD of 031 Hence 36 patients completing all sequences ie 6 ptsequence will provide 90 power to detect a 10 RHI relative change in the ticagrelor group with a two-sided alpha level at 5 To account for drop outs as well as incomplete data assessment at all time points a final sample size of 50 patients will be recruited
Patients will be provided with a regular drug prescription standard of care medication At each follow-up the investigator will collect information about adherence to the study drug and register the charge number of the prescribed P2Y12
Allocation of study treatment will be performed via a web-based interactive randomization system based on a computer-generated random sequence with a random block size stratified according to the type of P2Y12 inhibitor ticagrelor vs prasugrel vs clopidogrel as well as for the presence of diabetes mellitus
Adverse events are defined as any undesirable experience occurring to a subject during the study whether or not considered related to study All adverse events reported spontaneously by the subject or observed by the investigator or his staff will be recorded Serious adverse events in this study are considered to be extremely rare
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2014-004189-64 | EUDRACT_NUMBER | None | None |