Sugg RM et al. (2006) Argatroban tPA Stroke Study: study design and results in the first treated cohort. Arch Neurol 63: 1057–1062

Argatroban is a thrombin inhibitor that, in combination with recombinant tissue plasminogen activator (rtPA), improves the speed and completeness of recanalization in animal stroke models. Sugg et al. conducted a phase I study of argatroban and rtPA in 15 patients (mean age 61 years) with occlusion of the middle cerebral artery. The primary outcome of the trial was incidence of intracerebral hemorrhage; the secondary outcome was complete recanalization at 2 h.

Symptomatic hemorrhage occurred in two patients, and one patient had an asymptomatic hemorrhage. Six patients had complete recanalization at 2 h; partial recanalization was achieved in a further four patients. Reocclusion occurred in three patients, one of whom had subsequent recanalization. One patient died, as a result of malignant cerebral edema. At 7 days, the median NIH stroke score had improved to 3.5, from 14 at baseline. The recanalization rate of 71% compared favorably with the 38% achieved with the control patients of the CLOTBUST study, who were treated with rtPA alone. Patient numbers, however, were insufficient to reach statistical significance for the comparison.

The authors conclude that argatroban combined with rtPA has the potential to bring about faster and more complete recanalization in stroke patients than does rtPA alone. Phase II of the study is ongoing.