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

Sponsor

University of Ioannina (Other)

Overall Status

Completed

CT.gov ID

NCT02616497

Collaborator

(none)

1,220

Enrollment

Location

Arms

30.9

Duration (Months)

39.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Atherothrombosis	Drug: Aspirin Drug: Triflusal	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

1220 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Health Services Research

Official Title:

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

Study Start Date :

Sep 1, 2015

Actual Primary Completion Date :

Feb 28, 2017

Actual Study Completion Date :

Mar 28, 2018

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Composite of death from vascular causes, myocardial infarction (MI), or stroke (ischaemic or haemorrhagic) during the twelve month treatment period [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
Rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria during the twelve month treatment period [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

Secondary Outcome Measures

Composite of death from any cause, MI, or stroke during the twelve month treatment period [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
Hypersensitivity or intolerance to study drugs during the twelve month treatment period [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).