The Elderly ACS II Trial

Phase IV: A Comparison of Reduced-dose Prasugrel and Clopidogrel in Elderly Patients With Acute Coronary Syndrome Undergoing Early Percutaneous Coronary Intervention (PCI)

The objective of this study is to compare reduced-dose prasugrel and standard dose clopidogrel in patients older than 74 years with ACS, including non-ST-elevation (NSTEACS) and ST-elevation (STEMI) patients, undergoing early PCI. The primary endpoint of the trial will be the one-year composite of (all-cause)death, myocardial infarction, stroke and re-hospitalization due to cardiovascular reasons or bleeding.

Study Overview

• Status: Unknown
• Conditions: Myocardial Ischemia; Cardiovascular Diseases; Acute Coronary Syndrome; Coronary Arteriosclerosis
• Intervention / Treatment: Drug: prasugrel; Drug: Clopidogrel

• Study Type: Interventional
• Enrollment (Anticipated): 2000
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Stefano Savonitto, MD; Phone Number: +39-0341-489490; Email: s.savonitto@ospedale.lecco.it

Study Locations

• Italy
  • Reggio Emilia, Italy, 42123
    • Recruiting
    • Arcispedale Santa Maria Nuova- IRCCS
    • Contact: Stefano Savonitto, MD; Phone Number: +39-0341-489490; Email: s.savonitto@ospedale.lecco.it
    • Principal Investigator: Stefano Savonitto, MD
  • MI
    • Legnano, MI, Italy, 20025
      • Recruiting
      • Azienda Ospedaliera "Ospedale Civile di Legnano"
      • Contact: Stefano De Servi, MD; Email: stefano.deservi@ao-legnano.it
      • Principal Investigator: Stefano De Servi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 75 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- Patients >74 years of age hospitalized for an ACS, with or without STE, with an onset of symptoms during the previous 72 hours, and candidates to an early PCI.

• STEMI patients may be randomized upon first diagnosis, provided they do not meet any exclusion criteria. STEMI patients should not exceed 50 percent of the global population of the study

• Eligible NSTEACS patients may be randomized after coronary angiography. To be eligible, NSTEACS patients must have at least one of the following characteristics:

  • elevated troponin levels;
  • diabetes mellitus;
  • prior MI;
  • at least one new ischemic episode while on standard treatment during the index hospitalization;
  • ACS due to stent thrombosis.

Exclusion Criteria:

• History of stroke or transient ischemic attack (TIA)
• Gastrointestinal or genitourinary bleeding of clinical significance within 6 weeks prior to randomization.
• Hemoglobin level on admission <10 g/dl, unless this is considered to be secondary to renal dysfunction or known myelodysplasia.
• Secondary causes of acute myocardial ischemia.
• Known current platelet count < 90,000 cells/mL.
• Ongoing oral anticoagulant treatment or an INR known to be >1.5 at the time of screening.
• Concomitant severe obstructive lung disease, malignancy or neurologic deficit limiting follow-up or adherence to the study protocol.
• Participation in any phase of another clinical research study involving the evaluation of another investigational drug or device within 30 days prior to randomization
• Inability to give at least verbal informed consent to the study.
• Contraindications to the use of clopidogrel or prasugrel as per package leaflet.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: prasugrel; prasugrel 60 mg loading dose, followed by 5 mg once daily until the end of follow-up	Drug: prasugrel; prasugrel 5 mg o.d.; Other Names: Efient
ACTIVE_COMPARATOR: clopidogrel; Clopidogrel 300 mg loading dose followed by 75 mg once day until the end of follow-up	Drug: Clopidogrel; 75 mg o.d.; Other Names: Plavix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The composite of all-cause mortality, myocardial infarction (MI), disabling stroke and re-hospitalization for cardiovascular causes or bleeding within one year	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The composite of burden of recurrent cardiovascular (CV) events, CV mortality, all-cause mortality and MI, major bleeding, any stroke, total number of days spent in hospital.	definition of major bleeding: - Bleeding Academic Research Consortium (BARC) type 2 or 3 bleeding within 1 year (for bleedings occurring during index or subsequent hospitalizations) · BARC type IV bleeding within 1 year	1 year

Collaborators and Investigators

• Sponsor: Arcispedale Santa Maria Nuova-IRCCS
• Collaborators: Italian Society of Invasive Cardiology; ANMCO Italian Association of Hospital Cardiologist

Publications and helpful links

General Publications

• Crimi G, Morici N, Ferrario M, Ferri LA, Piatti L, Grosseto D, Cacucci M, Mandurino Mirizzi A, Toso A, Piscione F, De Carlo M, Elia LR, Trimarco B, Bolognese L, Bovenzi FM, De Luca G, Savonitto S, De Servi S. Time Course of Ischemic and Bleeding Burden in Elderly Patients With Acute Coronary Syndromes Randomized to Low-Dose Prasugrel or Clopidogrel. J Am Heart Assoc. 2019 Jan 22;8(2):e010956. doi: 10.1161/JAHA.118.010956.
• Savonitto S, Ferri LA, Piatti L, Grosseto D, Piovaccari G, Morici N, Bossi I, Sganzerla P, Tortorella G, Cacucci M, Ferrario M, Murena E, Sibilio G, Tondi S, Toso A, Bongioanni S, Ravera A, Corrada E, Mariani M, Di Ascenzo L, Petronio AS, Cavallini C, Vitrella G, Rogacka R, Antonicelli R, Cesana BM, De Luca L, Ottani F, De Luca G, Piscione F, Moffa N, De Servi S; Elderly ACS 2 Investigators. Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization. Circulation. 2018 Jun 5;137(23):2435-2445. doi: 10.1161/CIRCULATIONAHA.117.032180. Epub 2018 Feb 19.
• Ferri LA, Morici N, Grosseto D, Tortorella G, Bossi I, Sganzerla P, Cacucci M, Sibilio G, Tondi S, Toso A, Ferrario M, Gandolfo N, Ravera A, Mariani M, Corrada E, Di Ascenzo L, Petronio AS, Cavallini C, Moffa N, De Servi S, Savonitto S. A comparison of reduced-dose prasugrel and standard-dose clopidogrel in elderly patients with acute coronary syndromes undergoing early percutaneous revascularization: Design and rationale of the randomized Elderly-ACS 2 study. Am Heart J. 2016 Nov;181:101-106. doi: 10.1016/j.ahj.2016.08.010. Epub 2016 Aug 26.

Helpful Links

• Design and rationale of the randomized Elderly-ACS 2 study

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (ANTICIPATED): August 1, 2017
• Study Completion (ANTICIPATED): December 1, 2017

Study Registration Dates

• First Submitted: January 21, 2013
• First Submitted That Met QC Criteria: January 24, 2013
• First Posted (ESTIMATE): January 29, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): October 21, 2016
• Last Update Submitted That Met QC Criteria: October 19, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: elderly; acute coronary syndrome; percutaneous revascularization; antiaggregant drugs
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Vascular Diseases; Arterial Occlusive Diseases; Disease; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Cardiovascular Diseases; Syndrome; Ischemia; Arteriosclerosis; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; Prasugrel Hydrochloride
• Other Study ID Numbers: EudraCT Number: 2012-002882-37