Design and methodology of the ESPRIT trial: Evaluating a novel dosing regimen of eptifibatide in percutaneous coronary intervention

Background Clinical trials of the glycoprotein (GP) IIb/IIIa inhibitors hav e shown that these potent antiplatelet agents ore effective in reducing the ischemic complications of percutaneous coronary interventions. However, ev en though stents ore now implanted in >75% of percutaneous interventional p rocedures, only one study, a trial of the monoclonal antibody abciximab, ha s formally evaluated adjunctive GP IIb/IIIa inhibition in this setting. Methods and Results Eptifibatide, a nonimmunogenic and rapidly reversible i nhibitor of the platelet receptor integrin IIb/IIIa, has also undergone eva luation as an adjunct to coronary intervention. In clinical trials performe d heretofore, however, it has appeared to have less relative clinical effic acy than the monoclonal antibody abciximab. Since the early seminal trials, ii has been recognized that the doses of eptifibatide previously used achi eved only 30% to 50% of maximal platelet GP IIb/IIIa integrin inhibition. T his is considerably less than the 80% level of receptor inhibition that has been proposed to prevent coronary thrombus formation in animal models and that has been achieved in clinical trials with abciximab. Conclusions The Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial was designed to test the safety and effi cacy of a high-dose, "180/2.0/180" double-bolus regimen of eptifibatide (a 180-mug/kg bolus followed 10 minutes later by a second 180-mug/kg bolus of eptifibatide combined with a 2.0-mug/kg per minute infusion) as an adjunct to nonacute percutaneous coronary intervention with stent implantation. In this report, we review the rationale, design, and methods of this clinical investigation.