The Argatroban and tissue-type plasminogen activator stroke study

Final results of a pilot safety study

Andrew D. Barreto, Andrei Alexandrov, Pat Lyden, Jessica Lee, Sheryl Martin-Schild, Loren Shen, Tzu Ching Wu, April Sisson, Renganayaki Pandurengan, Zhongxue Chen, Mohammad H. Rahbar, Clotilde Balucani, Kristian Barlinn, Rebecca M. Sugg, Zsolt Garami, Georgios Tsivgoulis, Nicole R. Gonzales, Sean I. Savitz, Robert Mikulik, Andrew M. Demchuk & 1 others James C. Grotta

Research output: Contribution to journalArticle

58 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)770-775
Number of pages6
JournalStroke
Volume43
Issue number3
DOIs
StatePublished - Mar 1 2012

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Plasminogen Activators
Tissue Plasminogen Activator
Stroke
Safety
Cerebral Hemorrhage
Antithrombins
Partial Thromboplastin Time
National Institutes of Health (U.S.)
Hematoma
argatroban
Animal Models
Incidence

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

The Argatroban and tissue-type plasminogen activator stroke study : Final results of a pilot safety study. / Barreto, Andrew D.; Alexandrov, Andrei; Lyden, Pat; Lee, Jessica; Martin-Schild, Sheryl; Shen, Loren; Wu, Tzu Ching; Sisson, April; Pandurengan, Renganayaki; Chen, Zhongxue; Rahbar, Mohammad H.; Balucani, Clotilde; Barlinn, Kristian; Sugg, Rebecca M.; Garami, Zsolt; Tsivgoulis, Georgios; Gonzales, Nicole R.; Savitz, Sean I.; Mikulik, Robert; Demchuk, Andrew M.; Grotta, James C.

In: Stroke, Vol. 43, No. 3, 01.03.2012, p. 770-775.

Research output: Contribution to journalArticle

Barreto, AD, Alexandrov, A, Lyden, P, Lee, J, Martin-Schild, S, Shen, L, Wu, TC, Sisson, A, Pandurengan, R, Chen, Z, Rahbar, MH, Balucani, C, Barlinn, K, Sugg, RM, Garami, Z, Tsivgoulis, G, Gonzales, NR, Savitz, SI, Mikulik, R, Demchuk, AM & Grotta, JC 2012, 'The Argatroban and tissue-type plasminogen activator stroke study: Final results of a pilot safety study', Stroke, vol. 43, no. 3, pp. 770-775. https://doi.org/10.1161/STROKEAHA.111.625574
Barreto, Andrew D. ; Alexandrov, Andrei ; Lyden, Pat ; Lee, Jessica ; Martin-Schild, Sheryl ; Shen, Loren ; Wu, Tzu Ching ; Sisson, April ; Pandurengan, Renganayaki ; Chen, Zhongxue ; Rahbar, Mohammad H. ; Balucani, Clotilde ; Barlinn, Kristian ; Sugg, Rebecca M. ; Garami, Zsolt ; Tsivgoulis, Georgios ; Gonzales, Nicole R. ; Savitz, Sean I. ; Mikulik, Robert ; Demchuk, Andrew M. ; Grotta, James C. / The Argatroban and tissue-type plasminogen activator stroke study : Final results of a pilot safety study. In: Stroke. 2012 ; Vol. 43, No. 3. pp. 770-775.
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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.",
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T1 - The Argatroban and tissue-type plasminogen activator stroke study

T2 - Final results of a pilot safety study

AU - Barreto, Andrew D.

AU - Alexandrov, Andrei

AU - Lyden, Pat

AU - Lee, Jessica

AU - Martin-Schild, Sheryl

AU - Shen, Loren

AU - Wu, Tzu Ching

AU - Sisson, April

AU - Pandurengan, Renganayaki

AU - Chen, Zhongxue

AU - Rahbar, Mohammad H.

AU - Balucani, Clotilde

AU - Barlinn, Kristian

AU - Sugg, Rebecca M.

AU - Garami, Zsolt

AU - Tsivgoulis, Georgios

AU - Gonzales, Nicole R.

AU - Savitz, Sean I.

AU - Mikulik, Robert

AU - Demchuk, Andrew M.

AU - Grotta, James C.

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N2 - 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.

AB - 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.

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