Tailored Antiplatelet Therapy Versus Recommended Dose of Prasugrel

Acute Coronary Syndrome Clinical Trial

— ANTARCTIC  

Official title:

The ANTARCTIC Study - Assessment of a Normal Versus Tailored Dose of Prasugrel After Stenting in Patients Aged > 75 Years to Reduce the Composite of Bleeding, Stent Thrombosis and Ischemic Complications

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01538446
• Other study ID #: P110101
• Status: Completed
• Phase: Phase 4
• First received: February 20, 2012
• Last updated: January 10, 2017
• Start date: March 2012
• Est. completion date: May 2016

Study information

• Verified date: January 2017
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to demonstrate the superiority of a strategy of platelet monitoring (Monitoring Arm) with down-adjustment of the dose of prasugrel in high responders and up-adjustment of the dose of prasugrel in low responders as compared to a more conventional strategy of a fixed dose of 5 mg to every patient without monitoring (Conventional Arm) as measured by a reduction in the composite endpoint of, cardiovascular (CV) death, myocardial infarction (MI) , stroke, stent thrombosis (ARC definition type "definite"), urgent revascularisation or bleeding (BARC definition type 2, 3 or 5).

Description:

Objective: To demonstrate the superiority of a strategy of platelet monitoring (Monitoring Arm) with down-adjustment of the dose of prasugrel in high responders and up-adjustment of the dose of prasugrel in low responders as compared to a more conventional strategy of a fixed dose of 5 mg to every patient without monitoring (Conventional Arm).Rationale: Prasugrel 10 mg is superior to clopidogrel in patients with acute coronary syndrome treated by percutaneous coronary intervention, reducing significantly the rates of ischemic events. Elderly patients appear to be at higher risk of bleeding events and pharmacokinetic data suggests that elderly patients are exposed to a higher concentration of the active metabolite of prasugrel. A reduced dose of 5 mg of prasugrel is therefore proposed to these patients to limit the risk of bleeding. On the other hand, the elderly have also a higher ischemic risk and higher levels of platelet aggregation under treatment than younger patients and may deserve stronger protection from antiplatelet therapy. Platelet function testing appears to be of particular interest in patients at high risk of both ischemic and bleeding events like the elderly. Too intense platelet inhibition may expose the elderly patients to an excessive bleeding risk. Too low platelet inhibition may expose them to recurrent cardiovascular ischemic events. The possibility of bedside monitoring of oral antiplatelet therapy offers the opportunity of tailoring prasugrel therapy in elderly patients to optimize their risk/benefit ratio. Such strategy has never been evaluated in a randomized and adequately powered study. Population: Acute coronary syndrome (STEMI and NSTEMI) treated by PCI-stent (bare metal stent or drug eluting stent) in patients aged 75 ≥ year. Methods: Monitoring with VerifyNow P2Y12, 2 weeks after initiation of 5 mg of maintenance dose of prasugrel, reduction of antiplatelet therapy if there is high on-treatment platelet inhibition (HPI) or increase in dosing if there is high on-treatment platelet reactivity (HPR). Patients will be monitored again 2 weeks later, only if they do not meet the Verifynow P2Y12 targets at the first assessment. Primary endpoint net clinical benefit at 12 months:Composite of Cardiovascular death, myocardial infarction, stroke, urgent revascularisation, stent thrombosis and bleedings according to the BARC definitions (type 2, 3 or 5) Centers: Approximately 40 French high volume PCI centers

Recruitment information / eligibility

• Status: Completed
• Enrollment: 880
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 75 Years and older

Eligibility

Inclusion Criteria:

• Acute coronary syndrome (STEMI and NSTEMI) treated by PCI

• Stent (bare metal stent or drug eluting stent) regardless of the regime of thienopyridines administered before randomisation

• Age = 75 years.

• Aspirin dose of 75 mg will be recommended but study authorizes doses ranging from 75-160 mg

• Ability to understand and to comply with the study protocol.

• Written informed consent

Exclusion Criteria:

• Prior history of ischemic or hemorrhagic stroke or transient ischemic attack, or sub-arachnoids haemorrhage

• Have received fibrinolytic therapy within 48 hours of entry or randomisation into the study

• Are receiving vitamin K antagonist

• Concomitant medical illness (terminal malignancy) that is associated with reduced survival over the expected study treatment period.

• History of intolerance or allergy to ASA or approved thienopyridines (ticlopidine, clopidogrel, or prasugrel)

• Have active pathological bleeding or history of bleeding diathesis

• Thrombocytopenia < 100 000 µL

• Severe hepatic impairment (Child Pugh class C).

• Have a condition associated with poor treatment compliance, including dementia or mental illness

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Coronary Syndrome

Intervention

Drug:
• Modification of Prasugrel based on a biological assay
Monitoring with VerifyNow P2Y12, 2 weeks after initiation of 5 mg of maintenance dose of prasugrel, reduction of antiplatelet therapy if there is high on-treatment platelet inhibition (HPI) or increase in dosing if there is high on-treatment platelet reactivity (HPR) Device: VerifyNow point of care assay VerifyNow (ACCUMETRICS San Diego USA)
• prasugrel / clopidogrel
fixed dose of prasugrel 5 mg

Device:
• Verify Now
Monitoring with VerifyNow P2Y12, 2 weeks after initiation of 5 mg of maintenance dose of prasugrel, reduction of antiplatelet therapy if there is high on-treatment platelet inhibition (HPI) or increase in dosing if there is high on-treatment platelet reactivity (HPR) Device: VerifyNow point of care assay VerifyNow (ACCUMETRICS San Diego USA)

Locations

Country	Name	City	State
France	CHU Caremeau à Nimes - Service de Cardiologie	Nimes
France	ACTION study group - Institut de Cardiologie- Hôpital la Pitié Salpêtrière	Paris

Sponsors (6)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Accumetrics, Inc., Allies in Cardiovascular Trials Initiatives and Organized, Daiichi Sankyo Inc., Eli Lilly and Company, Stentys

Country where clinical trial is conducted

France, 

References & Publications (1)

Cayla G, Cuisset T, Silvain J, Leclercq F, Manzo-Silberman S, Saint-Etienne C, Delarche N, Bellemain-Appaix A, Range G, El Mahmoud R, Carrié D, Belle L, Souteyrand G, Aubry P, Sabouret P, du Fretay XH, Beygui F, Bonnet JL, Lattuca B, Pouillot C, Varenne O — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of Cardiovascular death, myocardial infarction, stroke, urgent revascularisation, stent thrombosis and bleedings according to the BARC definitions (type 2, 3 or 5) through 12 months of randomisation	Composite of Cardiovascular death, myocardial infarction, stroke, urgent revascularisation, stent thrombosis and bleedings according to the BARC definitions (type 2, 3 or 5) through 12 months of randomisation	through 12 months of randomisation	Yes
Secondary	Evaluation of the benefice of prasugrel adjustment on the composite ischemic endpoint of cardiovascular (CV) death, MI, definite stent thrombosis and Urgent revascularisation through 12 months of randomisation	The key secondary objective is to evaluate the benefice of prasugrel adjustment on the composite ischemic endpoint of cardiovascular (CV) death, MI, definite stent thrombosis and Urgent revascularisation through 12 months of randomisation	through 12 months of randomisation	No
Secondary	CV death, MI, stroke through 12 months of randomisation		through 12 months of randomisation	No
Secondary	CV death, MI, stroke or Urgent Revascularization through 12 months of randomisation		through 12 months of randomisation	No
Secondary	CV death: any death		12 months after randomization	No
Secondary	Any death or resuscitated cardiac death		12 months after randomization	No
Secondary	CV death or MI		12 months after randomization	No
Secondary	Definite stent thrombosis (ARC definition)		12 months after randomization	No
Secondary	All types of bleeding according to the BARC definitions 1, 2, 3, 4, 5		12 months after randomization	Yes
Secondary	BARC Bleeding of type 2, 3 or 5		12 months after randomization	Yes
Secondary	Bleeding TIMI major through 12 months of randomisation		through 12 months of randomisation	Yes
Secondary	GUSTO severe or moderate bleeding		12 months after randomization	Yes
Secondary	STEEPLE bleeding definitions (major, minor or both)		12 months after randomization	Yes
Secondary	ISTH bleeding definitions (major and clinically relevant non major)		12 months after randomization	Yes
Secondary	Bleeding TIMI minor		12 months after randomization	Yes
Secondary	Bleeding TIMI minimal		12 months after randomization	Yes
Secondary	Bleeding TIMI major, minor and combination		12 months after randomization	Yes