title: Redesigning TRACER trial after TRITON.
abstract: Designing of smart clinical trials is critical for regulatory approval and future drug utilization. Importantly, trial design should be reconsidered if the interim analyses suggest unexpected harm, or conflicting results were yielded from the other trials within the same therapeutic area. With regard to antiplatelet agents, the perfect example is redesigning of the ongoing PRoFESS trial by eliminating aspirin from clopidogrel arm after the earlier MATCH trial results became available. The goal was to aseess the unchanged TRACER trial design in light of the evidence yielded from the earlier completed TRITON trial. TRACER was designed as a triple versus dual antiplatelet trial in NSTEMI patients with no previous long-term outcome data supporting such aggressive strategy. TRITON data represented dual versus dual antiplatelet therapy, and became available before TRACER enrollment starts revealing prasugrel front-loaded early vascular benefit predominantly in STEMI patients with the growing over time bleeding and cancer risks. Moreover, large prasugrel NSTEMI TRITON cohort exhibited trend towards excess mortality in experimental arm warning against aggressive TRACER design. The long-term TRITON results in general, and especially in the NSTEMI patients challenge unchanged TRACER trial design. Applying dual, rather than triple antiplatelet therapy protocol modification should be considered in TRACER to minimize bleeding, cancer, and non-cardiovascular death risks.
authors.affiliation: HeartDrug™ Research Laboratories, Johns Hopkins University, Osler Medical Building, 7600 Osler Drive, Suite 307, Towson, MD 21204, United States. Electronic address: heartdrug@aol.com.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D001241:Aspirin / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D000077144:Clopidogrel; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use; D009369:Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use; D012107:Research Design; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin; C530299:vorapaxar
keywords: Clinical trials; Outcomes; Prasugrel; Trial design; Vorapaxar