ASpirin vs Triflusal for Event Reduction In Atherothrombosis Secondary Prevention (ASTERIAS) (ASTERIAS)

April 13, 2018 updated by: Alexandros Tselepis, University of Ioannina

Comparison of Triflusal With Aspirin in the Secondary Prevention of Atherothrombotic Events

Investigation of the efficacy and safety of triflusal in comparison with aspirin in patients with stable coronary artery disease (CAD) and in those with a history of an acute non-cardioembolic ischemic stroke.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Triflusal, 2-(acetyloxy)-4-(trifluoromethyl) benzoic acid, is an antiplatelet agent with a chemical structure similar to aspirin, but with a different pharmacokinetic and pharmacodynamic profile. The drug is administered orally and its bioavailability ranges from 83% to 100%. It binds almost entirely (99%) to plasma proteins and crosses readily organic barriers. Triflusal is deacetylated in the liver, forming its main metabolite 2-hydroxy-4-trifluoromethyl benzoic acid (HTB). In contrast to the inactive aspirin metabolite salicylic acid, HTB exhibits antiplatelet activity and has a long plasma half-life of approximately 40h. Triflusal irreversibly inhibits COX-1 and reduces TxA2 production, but to a lesser extent compared with aspirin. It inhibits COX-1 and AA metabolism selectively in platelets, preserving PGI2 synthesis in vascular endothelial cells 1. Except of platelet COX-1 triflusal and in particular HTB inhibit phosphodiesterase, the enzyme that degrades the cyclic nucleotides, cyclic adenosine monophosphate (c-AMP) and cyclic guanosine monophosphate (c-GMP), both of which inhibit platelet function.

Triflusal has similar to aspirin efficacy for the secondary prevention of vascular events in patients with acute myocardial infarction (MI) and stroke, while it reduces the incidence of intracranial and gastrointestinal haemorrhage compared with aspirin. It should be noted that triflusal is well tolerated in patients with aspirin-induced asthma.

Aspirin (acetyl salicylic acid) remains for over 50 years the cornerstone of antiplatelet therapy due to its proven clinical benefit and very good cost effectiveness profile. Aspirin selectively and irreversibly acetylates the hydroxyl group of a single serine residue at position 529 within the polypeptide chain of PGH synthase-1. Thus aspirin inhibits the COX-1 activity but it does not affect the hydroperoxidase activity PGH synthase-1. By blocking COX-1, the production of TXA2 is reduced, leading to reduced platelet aggregation. Aspirin improves clinical outcome in all cardiovascular syndromes in primary and secondary prevention, including acute events. In high-risk patients, aspirin substantially reduces the risk of vascular death by ~15% and non-fatal vascular events by ~30% as it reported by a meta-analysis of over 100 large-scale randomized trials. Several studies the last years have suggested that a proportion of patients (5 to 65%) exhibit a hyporesponsiveness (resistance) to aspirin treatment which could be associated with recurrent ischemic events. Aspirin resistance may result from several causes, such as low compliance, interference with non-steroid anti-inflammatory drugs (NSAIDS) and protein glycation occurring in type 2 diabetes mellitus. Increased platelet turnover observed in various diseases such as ACS, peripheral arterial disease and diabetic angiopathy associated with faster re-appearance of newly formed, non aspirinated platelets, may also account for aspirin resistance.

Although triflusal is chemically related to aspirin and has similar effectiveness, it appears to have a better tolerability profile than aspirin. Results from large-scale clinical trials and a meta-analysis suggest that its use may be preferable to that of aspirin, in several clinical settings where antiplatelet therapy is indicated. Furthermore, in selected populations, such as in geriatric patients, because of an increased risk of bleeding complications, in patients suffering from asthma, chronic sinusitis and nasal polyps, or in cases of aspirin resistance, triflusal may be a choice worth considering. Furthermore, when combination antiplatelet-fibrinolytic or antiplatelet-anticoagulant therapy is needed, clinical data support triflusal use based on its efficacy and better safety than aspirin. Unlike aspirin, triflusal, also, less likely affect the efficacy of antihypertensive drugs, especially angiotensin converting enzyme inhibitors. The aim of the present trial is to investigate the efficacy and safety of triflusal in comparison with aspirin in patients with stable coronary artery disease (CAD) and in those with a history of an acute non-cardioembolic ischemic stroke.

Study Type

Interventional

Enrollment (Actual)

1220

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
      • Ioannina, Greece, 45110
        • Atherothrombosis Research Centre / Laboratory of Biochemistry, University of Ioannina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with a stable coronary artery disease (CAD)
  • Patients with a history of non-cardioembolic ischemic stroke.

Exclusion Criteria:

  • Hypersensitivity reaction or contraindication to triflusal or aspirin
  • Active bleeding or history of severe bleeding (peptic ulcer, trauma or intracranial hemorrhage)
  • Blood coagulation disorders
  • Uncontrolled severe hypertension
  • Pregnancy or breastfeeding
  • Liver disease (alanine or aspartate aminotransferase more than 3 times the upper normal limit)
  • Malignancy that may potentially increase the risk of hemorrhage
  • Drug or alcohol abuse
  • HIV infection
  • Chronic disorders requiring long-term treatment with systemic nonsteroidal anti-inflammatory drugs (NSAIDs).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Aspirin
100mg/day
Drug: Aspirin
COX-1 inhibitor
Other Names:
  • Salospir
Active Comparator: Triflusal
300mg twice or 600mg once daily
Drug: Triflusal
COX-1 inhibitor
Other Names:
  • Aflen

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite of death from vascular causes, myocardial infarction (MI), or stroke (ischaemic or haemorrhagic) during the twelve month treatment period
Time Frame: 12 months
Number of participants who suffer from the primary efficacy end point which is the composite of death from vascular causes, myocardial infarction(MI), or stroke during the twelve month treatment period
12 months
Rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria during the twelve month treatment period
Time Frame: 12 months
Number of participants who suffer from the rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria during the twelve month treatment period
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite of death from any cause, MI, or stroke during the twelve month treatment period
Time Frame: 12 months
Number of participants who suffer from the secondary efficacy end point which is the composite of death from any cause, MI, or stroke during the twelve month treatment period
12 months
Hypersensitivity or intolerance to study drugs during the twelve month treatment period
Time Frame: 12 months
Number of participants who suffer from the secondary safety end points which are hypersensitivity or intolerance to study drugs during the twelve month treatment period
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Ioannina

Investigators

  • Principal Investigator: Alexandros Tselepis, MD, Atherothrombosis Research Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2015

Primary Completion (Actual)

February 28, 2017

Study Completion (Actual)

March 28, 2018

Study Registration Dates

First Submitted

November 20, 2015

First Submitted That Met QC Criteria

November 24, 2015

First Posted (Estimate)

November 30, 2015

Study Record Updates

Last Update Posted (Actual)

April 17, 2018

Last Update Submitted That Met QC Criteria

April 13, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Asp-Trifl-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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