Tailored Antiplatelet Therapy Versus Recommended Dose of Prasugrel

NCT01538446 | Completed Phase 4 DMC

• 1 other identifier: P110101
• Study Type: interventional
• Target: 880
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Acute Coronary Syndrome

Keywords

Elderly; Acute coronary syndrome; Percutaneous coronary intervention; Prasugrel; Platelet function test

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (16)

• 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

  through 12 months of randomisation

• CV death, MI, stroke through 12 months of randomisation

  through 12 months of randomisation

• CV death, MI, stroke or Urgent Revascularization through 12 months of randomisation

  through 12 months of randomisation

• CV death: any death

  12 months after randomization

• Any death or resuscitated cardiac death

  12 months after randomization

Study Arms (2)

1: Monitoring Arm

EXPERIMENTAL

Monitoring Arm: dose adjustment of prasugrel with down-adjustment of the dose of prasugrel in high responders and up-adjustment of the dose of prasugrel in low responders

Drug: Modification of Prasugrel based on a biological assay; Device: Verify Now

2: Conventional Arm

ACTIVE COMPARATOR

Conventional Arm: fixed dose of prasugrel 5 mg

Drug: prasugrel / clopidogrel

Interventions

Modification of Prasugrel based on a biological assay DRUG

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)

1: Monitoring Arm

prasugrel / clopidogrel DRUG

fixed dose of prasugrel 5 mg

2: Conventional Arm

Verify Now DEVICE

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)

1: Monitoring Arm

Eligibility Criteria

• Age: 75 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Eli Lilly and Company: collaborator
• Daiichi Sankyo: collaborator
• Allies in Cardiovascular Trials Initiatives and Organized: collaborator
• Accumetrics, Inc.: collaborator
• Stentys: collaborator

Study Sites (2)

CHU Caremeau à Nimes - Service de Cardiologie

Nîmes, 30029, France

Location

ACTION study group - Institut de Cardiologie- Hôpital la Pitié Salpêtrière

Paris, 75013, France

Location

Related Publications (3)

• Cayla G, Cuisset T, Silvain J, Leclercq F, Manzo-Silberman S, Saint-Etienne C, Delarche N, Bellemain-Appaix A, Range G, El Mahmoud R, Carrie D, Belle L, Souteyrand G, Aubry P, Sabouret P, du Fretay XH, Beygui F, Bonnet JL, Lattuca B, Pouillot C, Varenne O, Boueri Z, Van Belle E, Henry P, Motreff P, Elhadad S, Salem JE, Abtan J, Rousseau H, Collet JP, Vicaut E, Montalescot G; ANTARCTIC investigators. Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trial. Lancet. 2016 Oct 22;388(10055):2015-2022. doi: 10.1016/S0140-6736(16)31323-X. Epub 2016 Aug 28.

  PMID: 27581531 RESULT

• Lattuca B, Cayla G, Silvain J, Cuisset T, Leclercq F, Manzo-Silberman S, Saint-Etienne C, Delarche N, El Mahmoud R, Carrie D, Souteyrand G, Kerneis M, Hauguel-Moreau M, Zeitouni M, Guedeney P, Diallo A, Collet JP, Vicaut E, Montalescot G; ACTION Study Group. Bleeding in the Elderly: Risk Factors and Impact on Clinical Outcomes After an Acute Coronary Syndrome, a Sub-study of the Randomized ANTARCTIC Trial. Am J Cardiovasc Drugs. 2021 Nov;21(6):681-691. doi: 10.1007/s40256-021-00468-8. Epub 2021 Jun 30.

  PMID: 34191259 DERIVED

• Cayla G, Cuisset T, Silvain J, Henry P, Leclercq F, Carrie D, Etienne CS, Belle L, Range G, Pouillot C, Varenne O, Van Belle E, Boueri Z, Motreff P, Elhadad S, Delarche N, El Mahmoud R, Vicaut E, Collet JP, Montalescot G; ANTARCTIC investigators. Platelet function monitoring in elderly patients on prasugrel after stenting for an acute coronary syndrome: design of the randomized antarctic study. Am Heart J. 2014 Nov;168(5):674-81. doi: 10.1016/j.ahj.2014.07.026. Epub 2014 Aug 7.

  PMID: 25440795 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

Prasugrel Hydrochloride; Clopidogrel

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ticlopidine; Thienopyridines; Pyridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Gilles MONTALESCOT, MD,PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2012
• First Posted: February 24, 2012
• Study Start: March 1, 2012
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: January 11, 2017

Record last verified: 2017-01

Locations

FR (2)