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.