Ignite Creation Date:
2024-05-06 @ 3:44 PM
Last Modification Date:
2024-10-26 @ 1:56 PM
Study NCT ID:
NCT04739384
Status:
COMPLETED
Last Update Posted:
2022-07-07
First Post:
2020-12-28
Brief Title:
Platelet Inhibition With Ticagrelor 60 mg Versus Ticagrelor 90 mg in Elderly Patients With ACS
Sponsor:
Federico II University
Organization:
Federico II University
Study Overview
Official Title:
Platelet Inhibition With Ticagrelor 60 mg Versus Ticagrelor 90 mg Twice Daily in Elderly Patients With Acute Coronary Syndrome ACS
Status:
COMPLETED
Status Verified Date:
2022-07
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:
PlinytheElder
Brief Summary:
Elderly individuals are increasingly represented among patients with acute coronary syndrome ACS Dual antiplatelet therapy DAPT with aspirin and an oral P2Y12 receptor inhibitor has an established role in the prevention of atherothrombotic events in ACS setting However DAPT in older patients is challenged by a concurrent heightened risk of ischemia and bleeding Although guidelines recommend DAPT with aspirin and ticagrelor for elderly patients with ACS clopidogrel a less potent antiplatelet agent continues to be used in more than one third of ACS patients with elderly status being the strongest predictor of undertreatment A lower dose of ticagrelor may represent an alternative to the standard dose by conferring a similar efficacy and potentially a better safety profile Our prospective randomized double-blind crossover trial will test the hypothesis that a lower dose of ticagrelor provides similar antiplatelet effects compared with a standard dose among elderly patients with ACS
The main aim of the trial is to determine the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 mg twice daily versus ticagrelor 90 mg twice daily among elderly patients with ACS undergoing PCI
This will be a prospective randomized 11 ratio non-inferiority open-label crossover trial to evaluate the level of platelet inhibition achieved with a low-dose of ticagrelor 60 mg twice daily versus a standard dose of ticagrelor 90 mg twice daily among elderly patients with ACS undergoing PCI
The main aim of the trial is to determine the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 mg twice daily versus ticagrelor 90 mg twice daily among elderly patients with ACS undergoing PCI
This will be a prospective randomized 11 ratio non-inferiority open-label crossover trial to evaluate the level of platelet inhibition achieved with a low-dose of ticagrelor 60 mg twice daily versus a standard dose of ticagrelor 90 mg twice daily among elderly patients with ACS undergoing PCI
Detailed Description:
Elderly individuals account for an increasing proportion of patients with acute coronary syndrome ACS undergoing percutaneous coronary intervention PCI given the aging of the population and the lengthening of life expectancy1 2 Dual antiplatelet therapy with aspirin and an oral P2Y12 receptor inhibitor is the cornerstone of antithrombotic therapy in patients with ACS undergoing PCI yet decision-making in older patients remains challenging because of a concomitantly increased risk of bleeding and ischemic complications burdening this population3 Elderly status may be considered per se a condition at heightened risk of bleeding since by applying available risk scores patients aged 75 years or more who undergo PCI are classified as moderate-to-high risk of bleeding irrespective of other additional features4 Current guidelines recommend DAPT in the setting of ACS and ticagrelor an oral reversible direct-acting P2Y12 receptor inhibitor should be preferred to clopidogrel and prasugrel among elderly patients5 Nevertheless observational studies have consistently shown that new P2Y12 receptor inhibitors continue to be withheld in more than one third of eligible patients with ACS and that aging is the most powerful predictor of undertreatment with clopidogrel6 This occurs for several reasons including adverse bleeding events or nonbleeding events a perceived too high bleeding risk and the higher risk profile of elderly patients seen in clinical practice compared with that in randomized trials Therefore alternative antithrombotic strategies should be pursued for elderly patients with ACS in order to minimize the harmful effects of more potent antiplatelet inhibition without withholding the established ischemic benefit At this regard a standard dose of prasugrel 10 mg daily resulted in a negative net benefit among elderly patients with ACS and a lower dose of prasugrel 5 mg daily did not prove safer or more effective than clopidogrel7 8 Since the risk-benefit profile of a full dose of ticagrelor 90 mg twice daily seemed more favorable among elderly individuals a lower dose regimen of ticagrelor 60 mg twice daily has the potential to improve the safety profile of potent P2Y12 receptor inhibition while providing an equally effective option
A low-dose of ticagrelor has been evaluated in the PEGASUS-TIMI 54 trial in which 21162 patients who were on aspirin and had a myocardial infarction 1 to 3 years earlier were randomized to ticagrelor at a dose of 90 mg twice daily ticagrelor at a dose of 60 mg daily or placebo The primary efficacy endpoint of cardiovascular death myocardial infarction and stroke through 3 years was significantly reduced by 15 and 16 among patients randomized to standard and low-dose of ticagrelor compared with placebo Patients randomly allocated to the standard and low dose of ticagrelor had a 169 and 132 relative risk increase in major bleeding compared with placebo Of interest ticagrelor 90 mg vs placebo had the greatest benefit for the primary efficacy endpoint among younger than older patients 20 relative risk reduction vs 2 relative risk increase respectively whereas ticagrelor 60 mg vs placebo had the greatest benefit for the primary efficacy endpoint among older than younger patients 23 relative risk reduction vs 14 relative risk reduction respectively For the safety profile elderly patients had roughly a 2-fold higher incidence of bleeding compared with younger patients with ticagrelor 90 mg being associated with the highest rate of bleeding 481 Conversely ticagrelor 60 mg was associated with a lower incidence of major bleeding -07 absolute difference compared with ticagrelor 90 mg even though major bleeding events were increased compared with placebo 243 absolute difference9 Taken together the data from the PEGASUS-TIMI 54 suggest ticagrelor 60 mg twice daily may present the best combination of efficacy and safety for elderly patients
Although no specific data are available for ticagrelor 60 mg among elderly patients with ACS a substudy of the PEGASUS- TIMI 54 trial showed that ticagrelor 60 mg twice daily achieved a platelet inhibition similar to that with 90 mg twice daily PRU values 5963 and 4743 for ticagrelor 60 and 90 mg twice daily respectively10 Noteworthy these data have been observed in a relatively younger population mean age 64 years with stable coronary artery disease after nearly 2 years from the index myocardial infarction10 Consequently the findings of the PEGASUS-TIMI 54 trial cannot be directly extrapolated to our population with since both elderly status and ACS are associated with higher platelet reactivity
Primary Objectives the main aim of the trial is to determine whether the efficacy of ticagrelor 60 mg twice daily is not inferior to that of ticagrelor 90 mg twice daily among elderly patients with ACS undergoing PCI
Secondary Objectives To evaluate adverse events in patients treated with ticagrelor 60 mg and ticagrelor 90 mg To determine the pharmacokinetic profile of ticagrelor 60 mg twice daily versus ticagrelor 90 mg twice daily
This will be a prospective randomized 11 ratio non-inferiority open-label crossover trial to evaluate the level of platelet inhibition achieved with a low-dose of ticagrelor 60 mg twice daily versus a standard dose of ticagrelor 90 mg twice daily among elderly patients with ACS undergoing PCI The study will have a 2 x 2 crossover design with 2-sequence 2-period and 2-treatments
After signing the informed consent form patients will be randomized to ticagrelor 60 mg twice daily vs ticagrelor 90 mg twice daily in a 11 ratio through a web-based randomization system
Each patient will be allocated to the following treatments in a open-label fashion
Ticagrelor 90 mg twice daily followed by ticagrelor 60 mg twice daily
Ticagrelor 60 mg twice daily followed by ticagrelor 90 mg twice daily
The study duration for each individual patient will amount to 28 days consisting of
A 2-week first treatment period from day 1 to day 14 randomly allocated treatment will be maintained for 14 days
A 2-week second treatment period from day 15 to day 28 the patients will crossover to the alternative treatment which is administered for 14 days
Aspirin 100 mg once daily is maintained throughout all the study phases
Blood sampling to evaluate adenosine diphosphate ADP e non-ADP platelet aggregation will be performed at 3 time points
Time 1 baseline before randomization
Time 2 crossover 14 days after randomization including 2 samples before and 2 hours after the last dose of the initial assigned treatment
Time 3 end of study 28 days after randomization including 2 samples before and 2 hours after the last dose of the second assigned treatment
Platelet function will be assessed by using several platelet function tests i VerifyNow P2Y12 VN-P2Y12 ii Light transmittance aggregometry LTA iii Multiplate electrode aggregometry MEA
A low-dose of ticagrelor has been evaluated in the PEGASUS-TIMI 54 trial in which 21162 patients who were on aspirin and had a myocardial infarction 1 to 3 years earlier were randomized to ticagrelor at a dose of 90 mg twice daily ticagrelor at a dose of 60 mg daily or placebo The primary efficacy endpoint of cardiovascular death myocardial infarction and stroke through 3 years was significantly reduced by 15 and 16 among patients randomized to standard and low-dose of ticagrelor compared with placebo Patients randomly allocated to the standard and low dose of ticagrelor had a 169 and 132 relative risk increase in major bleeding compared with placebo Of interest ticagrelor 90 mg vs placebo had the greatest benefit for the primary efficacy endpoint among younger than older patients 20 relative risk reduction vs 2 relative risk increase respectively whereas ticagrelor 60 mg vs placebo had the greatest benefit for the primary efficacy endpoint among older than younger patients 23 relative risk reduction vs 14 relative risk reduction respectively For the safety profile elderly patients had roughly a 2-fold higher incidence of bleeding compared with younger patients with ticagrelor 90 mg being associated with the highest rate of bleeding 481 Conversely ticagrelor 60 mg was associated with a lower incidence of major bleeding -07 absolute difference compared with ticagrelor 90 mg even though major bleeding events were increased compared with placebo 243 absolute difference9 Taken together the data from the PEGASUS-TIMI 54 suggest ticagrelor 60 mg twice daily may present the best combination of efficacy and safety for elderly patients
Although no specific data are available for ticagrelor 60 mg among elderly patients with ACS a substudy of the PEGASUS- TIMI 54 trial showed that ticagrelor 60 mg twice daily achieved a platelet inhibition similar to that with 90 mg twice daily PRU values 5963 and 4743 for ticagrelor 60 and 90 mg twice daily respectively10 Noteworthy these data have been observed in a relatively younger population mean age 64 years with stable coronary artery disease after nearly 2 years from the index myocardial infarction10 Consequently the findings of the PEGASUS-TIMI 54 trial cannot be directly extrapolated to our population with since both elderly status and ACS are associated with higher platelet reactivity
Primary Objectives the main aim of the trial is to determine whether the efficacy of ticagrelor 60 mg twice daily is not inferior to that of ticagrelor 90 mg twice daily among elderly patients with ACS undergoing PCI
Secondary Objectives To evaluate adverse events in patients treated with ticagrelor 60 mg and ticagrelor 90 mg To determine the pharmacokinetic profile of ticagrelor 60 mg twice daily versus ticagrelor 90 mg twice daily
This will be a prospective randomized 11 ratio non-inferiority open-label crossover trial to evaluate the level of platelet inhibition achieved with a low-dose of ticagrelor 60 mg twice daily versus a standard dose of ticagrelor 90 mg twice daily among elderly patients with ACS undergoing PCI The study will have a 2 x 2 crossover design with 2-sequence 2-period and 2-treatments
After signing the informed consent form patients will be randomized to ticagrelor 60 mg twice daily vs ticagrelor 90 mg twice daily in a 11 ratio through a web-based randomization system
Each patient will be allocated to the following treatments in a open-label fashion
Ticagrelor 90 mg twice daily followed by ticagrelor 60 mg twice daily
Ticagrelor 60 mg twice daily followed by ticagrelor 90 mg twice daily
The study duration for each individual patient will amount to 28 days consisting of
A 2-week first treatment period from day 1 to day 14 randomly allocated treatment will be maintained for 14 days
A 2-week second treatment period from day 15 to day 28 the patients will crossover to the alternative treatment which is administered for 14 days
Aspirin 100 mg once daily is maintained throughout all the study phases
Blood sampling to evaluate adenosine diphosphate ADP e non-ADP platelet aggregation will be performed at 3 time points
Time 1 baseline before randomization
Time 2 crossover 14 days after randomization including 2 samples before and 2 hours after the last dose of the initial assigned treatment
Time 3 end of study 28 days after randomization including 2 samples before and 2 hours after the last dose of the second assigned treatment
Platelet function will be assessed by using several platelet function tests i VerifyNow P2Y12 VN-P2Y12 ii Light transmittance aggregometry LTA iii Multiplate electrode aggregometry MEA
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None