The argatroban and tissue-type plasminogen activator stroke study: final results of a pilot safety study.
Publication/Presentation Date
3-1-2012
Abstract
BACKGROUND AND PURPOSE: Argatroban is a direct thrombin inhibitor that safely augments recanalization achieved by tissue-type plasminogen activator (tPA) in animal stroke models. The Argatroban tPA Stroke Study was an open-label, pilot safety study of tPA plus Argatroban in patients with ischemic stroke due to proximal intracranial occlusion.
METHODS: During standard-dose intravenous tPA, a 100-μg/kg bolus of Argatroban and infusion for 48 hours was adjusted to a target partial thromboplastin time of 1.75× baseline. The primary outcome was incidence of significant intracerebral hemorrhage defined as either symptomatic intracerebral hemorrhage or Parenchymal Hematoma Type 2. Recanalization was measured at 2 and 24 hours by transcranial Doppler or CT angiography.
RESULTS: Sixty-five patients were enrolled (45% men, mean age 63±14 years, median National Institutes of Health Stroke Scale=13). The median (interquartile range) time tPA to Argatroban bolus was 51 (38-60) minutes. Target anticoagulation was reached at a median (interquartile range) of 3 (2-7) hours. Significant intracerebral hemorrhage occurred in 4 patients (6.2%; 95% CI, 1.7-15.0). Of these, 3 were symptomatic (4.6%; 95% CI, 0.9-12.9). Seven patients (10%) died in the first 7 days. Within the 2-hour monitoring period, transcranial Doppler recanalization (n=47) occurred in 29 (61%) patients: complete in 19 (40%) and partial in another 10 (21%).
CONCLUSIONS: The combination of Argatroban and intravenous tPA is potentially safe in patients with moderate neurological deficits due to proximal intracranial arterial occlusions and may produce more complete recanalization than tPA alone. Continued evaluation of this treatment combination is warranted.
CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00268762.
Volume
43
Issue
3
First Page
770
Last Page
775
ISSN
1524-4628
Published In/Presented At
Barreto, A. D., Alexandrov, A. V., Lyden, P., Lee, J., Martin-Schild, S., Shen, L., Wu, T. C., Sisson, A., Pandurengan, R., Chen, Z., Rahbar, M. H., Balucani, C., Barlinn, K., Sugg, R. M., Garami, Z., Tsivgoulis, G., Gonzales, N. R., Savitz, S. I., Mikulik, R., Demchuk, A. M., … Grotta, J. C. (2012). The argatroban and tissue-type plasminogen activator stroke study: final results of a pilot safety study. Stroke, 43(3), 770–775. https://doi.org/10.1161/STROKEAHA.111.625574
Disciplines
Medicine and Health Sciences
PubMedID
22223235
Department(s)
Department of Medicine
Document Type
Article