Randomized, Multicenter Trial of ARTSS-2 (Argatroban With Recombinant Tissue Plasminogen Activator for Acute Stroke)

Abstract

Background and Purpose We conducted a randomized exploratory study to assess safety and the probability of a favorable outcome with adjunctive argatroban, a direct thrombin-inhibitor, administered to rt-PA treated ischemic stroke patients. Methods Patients treated with standard-dose rt-PA, not receiving endovascular therapy, were randomized to receive no argatroban or argatroban (100-μg/kg bolus) followed by infusion of either 1 μg/kg/min (low-dose) or 3 μg/kg/min (high-dose) for 48 hours. Safety was incidence of symptomatic intracerebral hemorrhage (sICH). Probability of clinical benefit (mRS 0–1 at 90-days) was estimated using a conservative Bayesian Poisson model (neutral prior probability centered at relative risk [RR]=1.0 and 95% prior intervals: 0.33–3.0). Results Ninety patients were randomized: 29 to rt-PA alone, 30 to rt-PA + low-dose argatroban, and 31 to rt-PA + high-dose argatroban. Rates of sICH were similar among control, low-dose and high-dose arms: 3/29 (10%); 4/30 (13%); and 2/31 (7%), respectively. At 90-days 6 (21%) rt-PA alone; 9 (30%) low-dose, and 10 (32%) high-dose patients were mRS 0–1. The RR (95% Credible Interval) for mRS 0–1 with low, high, and either low or high dose argatroban was 1.17 (0.57, 2.37), 1.27 (0.63, 2.53), and 1.34 (0.68, 2.76). The probability that adjunctive argatroban was superior to rt-PA alone was 67%, 74%, and 79% for low, high, and low or high dose, respectively. Conclusions In patients treated with rt-PA, adjunctive argatroban was not associated with increased risk of sICH and provides evidence that a definitive effectiveness trial is indicated.

Late Embolism Following Recanalization of Occluded Extracranial Internal Carotid Artery Dissection

“…It has been reported that the combination of IV-tPA and argatroban is effective and safe against acute ischemic stroke (AIS). 18) It has also been reported that IV-tPA was effective and safe against AIS caused by CeAD. 19) Cohen et al reported findings on EVS for iLAO caused by eICAD.…”

Intravenous Thrombolytic Therapy in Acute Stroke: Frequent Systemic Problems and Solutions

“…The symptomatic ICH rates were 10%, 13%, and 7%, respectively. The rates of those with mRS 0-1 in the third month were 21%, 30%, and 32%, respectively (48). Therefore, this combination is practical and safe and should be tested in further studies.…”

Response by Barreto and Grotta to Letter Regarding Article, “Randomized, Multicenter Trial of ARTSS-2 (Argatroban With Recombinant Tissue Plasminogen Activator for Acute Stroke)”

“…1 Compared to r-tPA alone, ARTSS-2 demonstrated safety and improved clinical outcomes in patients that received combination r-tPA and argatroban. In general, we are in complete agreement with Dr. Shah’s comments and would like to make the following points.…”