Intravenous tissue plasminogen activator (IV tPA) is an effective medical therapy for acute ischemic stroke, but recanalization rates of large arterial occlusions with tPA is only 50%. Combination treatment with tPA and eptifibatide, a glycoprotein 2b/3a inhibitor, has previously been studied and reported in the CLEAR trial, on the premise that delivering a platelet aggregation inhibitor together with tPA might augment clot lysis, although no benefit was seen. A follow up study, the CLEAR-ER study, was suggestive of a direction in favor of combination therapy when tPA was used at a higher dose of 0.6 mg/kg and eptifibatide was bloused as a higher dose of 135 ug/kg. In order to proceed to a phase 3 trial of full dose tPA with eptifibatide, the researchers here look at the rates of symptomatic ICH (sICH) as a complication of therapy in a protocol using full dose tPA of 0.9 mg/kg with high dose eptifibatide.
The primary purpose of this study is to demonstrate safety in terms of sICH rates only, not to determine functional outcome. Researchers established a pre-determined stopping point of 3 events out of 19 patients, or 4 events of 29 patients, which would be consistent with sICH rate less than 8%, equal to that seen in the NINDS trial. Enrollment stopped at 27 patients, with only one patient having developed sICH. The number of patients enrolled was not sufficient to determine functional outcomes; however, the study does demonstrate that full dose tPA with full dose eptifibatide is safe and feasible for use.
In the near-future, could we be using tPA together with eptifibatide on our patients prior to sending them on their way to endovascular treatment? If the phase 3 trial shows improved recanalization rates with a similarly preserved safety profile, this could potentially alter the landscape of acute ischemic stroke treatment and lend an additional medical therapy toward the armory of the vascular neurologist.
Tweet: Safety of full dose tPA and eptifibatide: results from the CLEAR-FDR trial
