Gastrointestinal safety of triflusal solution in healthy volunteers: a proof of concept endoscopic study

Abstract

Pourpose: Triflusal is an antiplatelet agent that irreversibly acetylates cyclooxygenase isoform 1 (COX-1) and therefore inhibits thromboxane biosynthesis. Triflusal was initially 2 marketed as capsules containing 300 mg of active substance. In 2006 a new oral 600 mg (10 ml) oral solution form of triflusal was authorized in Spain. The primary aim of this study was to compare the gastrointestinal safety of triflusal oral solution with triflusal capsules in healthy volunteers.Methods: Sixty healthy subjects were randomly assigned, in a 2.5 : 2.5 : 1 ratio, into three groups with 25 subjects receiving one bottle of triflusal oral solution (600 mg) daily, 25 subjects receiving two triflusal capsules (600 mg) once daily, and 10 subjects receiving two placebo capsules once daily, respectively, during seven consecutive days. Gastroscopy was performed at base line before administration of study drugs and after 4-8 hours of the last dose of study drugs. Effects on esophagus, stomach and duodenum were measured in accordance with a modified Lanza scale. Results:At baseline no differences between groups were detected. After treatment, median global scores in the placebo, triflusal solution and triflusal capsules groups were, respectively, 0, 1, and 3 (p = 0.003 for comparison between placebo and triflusal capsules and p= 0.042 for comparison between triflusal solution and triflusal capsules). There were no significant differences between triflusal solution and placebo. All treatments were well tolerarted. Conclusion:In healthy subjects, triflusal solution induced less endoscopically apparent gastrointestinal mucosal damage than triflusal capsules and did not induce more damage than placebo in healthy volunteers.

Frequency and Types of Pathological Upper Gastrointestinal Endoscopy Findings in Clinically Healthy Individuals

“…Fiberglass endoscopy was then the common method but had a lower resolution and thus sensitivity to detect pathological findings [11,13,14,20]. For the above-mentioned results of EGDs in healthy, symptom-free volunteers, no details are provided on used gastroscopic devices [17,46,49,51], except for one study in asymptomatic healthy volunteers in which the use of a fiberglass gastroscope was described [50].…”

“…It may serve as an indicator for the probability that respective lesions may develop spontaneously, and provide a reference for both the assessment of a drug as a potentially causative agent and for defining a finding as indicative of a disease process that may require treatment and/or follow-up. Indeed, EGD has been used as a method to assess gastrointestinal safety in a large number of clinical trials in healthy volunteers [11][12][13][14][15][16][17][18][19]. In these studies, the results for potential adverse treatment effects in eligible subjects were assessed, but data on respective screening failures were not reported.…”

“…In these studies, the results for potential adverse treatment effects in eligible subjects were assessed, but data on respective screening failures were not reported. Several controlled clinical trials reported results of repeated EGD after intake of placebo, but no data about screening failures was reported in these studies either [11,17,20,21]. Evaluation of relevant data on GI status in clinically healthy volunteers before inclusion in a clinical trial therefore provides important additional information on the background variability of respective findings.…”

The synergistic effect of EPA and DHA with cyclooxygenase-1 inhibitors on platelet aggregation

“…Triflusal inhibits irreversibly the COX-1 activity but to a lesser extent compared with ASA [21][22][23] . Due to these characteristics, triflusal exerts a comparable efficacy but with a safer profile compared to ASA 24,25 . Several clinical trials have designed to highlight triflusal as a promising alternative drug versus ASA [14][15][16]26 .…”