(Stroke. 1999;30:2598.)
© 1999 American Heart Association, Inc.
Original Contributions |
Combined Intravenous and Intra-Arterial r-TPA Versus Intra-Arterial Therapy of Acute Ischemic Stroke
Emergency Management of Stroke (EMS) Bridging Trial
From Henry Ford Health Sciences Center, Department of Emergency Medicine (C.A.L.); Emory University, Department of Neurology (M.F.); University of Cincinnati, Departments of Radiology, Division of Neuroradiology (T.A.T.), Neurology (J.B.), Emergency Medicine (J.S.), and Environmental Health (J.K.); Barrow Neurological Institute (J.F.), Oregon Health Sciences University, Department of Neurology (W.C.); University of California Los Angeles, Departments of Emergency Medicine and Neurology (S.S.); University of Texas Houston, Department of Neurology (J.G.); and Mayo Clinic Jacksonville, Department of Neurology (T.B.).
Correspondence to Thomas Brott, MD, Mayo Clinic Jacksonville, Department of Neurology, 4500 San Pablo Rd, Jacksonville, FL 32224. E-mail Brott.thomas{at}mayo.edu
Background and Purpose—The purpose of this study was to test the feasibility, efficacy, and safety of combined intravenous (IV) and local intra-arterial (IA) recombinant tissue plasminogen activator (r-TPA) therapy for stroke within 3 hours of onset of symptoms.
Methods—This was a double-blind, randomized, placebo-controlled multi-center Phase I study of IV r-TPA or IV placebo followed by immediate cerebral arteriography and local IA administration of r-TPA by means of a microcatheter. Treatment activity was assessed by improvement on the National Institutes of Health Stroke Scale Score (NIHSSS) at 7 to 10 days. The Barthel Index, modified Rankin Scale, and the Glasgow Outcome Scale measured 3-month functional outcome. Arterial recanalization rates and their relation to total r-TPA dose and time to lysis were measured. Rates of life-threatening bleeding, intracerebral hemorrhage (ICH), or other bleeding complications assessed safety.
Results—Thirty-five patients were randomly assigned, 17 into the IV/IA group and 18 into the placebo/IA group. There was no difference in the 7- to 10-day or the 3-month outcomes, although there were more deaths in the IV/IA group. Clot was found in 22 of 34 patients. Recanalization was better (P=0.03) in the IV/IA group with TIMI 3 flow in 6 of 11 IV/IA patients versus 1 of 10 placebo/IA patients and correlated to the total dose of r-TPA (P=0.05). There was no difference in the median treatment intervals from time of onset to IV treatment (2.6 vs 2.7 hours), arteriography (3.3 vs 3.0 hours), or clot lysis (6.3 vs 5.7 hours) between the IV/IA and placebo/IA groups, respectively. A direct relation between NIHSSS and the likelihood of the presence of a clot was identified. Eight ICHs occurred; all were hemorrhagic infarctions. There were no parenchymal hematomas. Symptomatic ICH within 24 hours occurred in 1 placebo/IA patient only. Beyond 24 hours, symptomatic ICH occurred in 2 IV/IA patients only. Life-threatening bleeding complications occurred in 2 patients, both in the IV/IA group. Moderate to severe bleeding complications occurred in 2 IV/IA patients and 1 placebo/IA patient.
Conclusions—This pilot study demonstrates combined IV/IA treatment is feasible and provides better recanalization, although it was not associated with improved clinical outcomes. The presence of thrombus on initial arteriography was directly related to the baseline NIHSSS. This approach is technically feasible. The numbers of symptomatic ICH were similar between the 2 groups, which suggests that this approach may be safe. Further study is needed to determine the safety and effectiveness of this new method of treatment. Such studies should address not only efficacy and safety but also the cost-benefit ratio and quality of life, given the major investment in time, personnel, and equipment required by combined IV and IA techniques.
Key Words: cerebral ischemia • cerebrovascular disorders • drug therapy, combination • stroke, acute • tissue plasminogen activator • thrombolytic therapy
This article has been cited by other articles:
 |
|
 |
|
  B. Nazliel, S. Starkman, D. S. Liebeskind, B. Ovbiagele, D. Kim, N. Sanossian, L. Ali, B. Buck, P. Villablanca, F. Vinuela, et al. A Brief Prehospital Stroke Severity Scale Identifies Ischemic Stroke Patients Harboring Persisting Large Arterial Occlusions Stroke, August 1, 2008; 39(8): 2264 - 2267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sugiura, K. Iwaisako, S. Toyota, and H. Takimoto Simultaneous Treatment with Intravenous Recombinant Tissue Plasminogen Activator and Endovascular Therapy for Acute Ischemic Stroke Within 3 Hours of Onset AJNR Am. J. Neuroradiol., June 1, 2008; 29(6): 1061 - 1066. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Nichols, P. Khatri, T. Tomsick, and J. Broderick Advantages of a Combined Approach to Recanalization Therapy Stroke, April 1, 2008; 39(4): e71 - e71. [Full Text] [PDF]
|
|
|
|
|
|
L. Valvassori, A. Ciccone, and R. Sterzi Response to Letter by Nichols et al Stroke, April 1, 2008; 39(4): e72 - e72. [Full Text] [PDF]
|
|
|
|
|
|
J. E. Acker III, A. M. Pancioli, T. J. Crocco, M. K. Eckstein, E. C. Jauch, H. Larrabee, N. M. Meltzer, W. C. Mergendahl, J. W. Munn, S. M. Prentiss, et al. Implementation Strategies for Emergency Medical Services Within Stroke Systems of Care: A Policy Statement From the American Heart Association/ American Stroke Association Expert Panel on Emergency Medical Services Systems and the Stroke Council Stroke, November 1, 2007; 38(11): 3097 - 3115. [Full Text] [PDF]
|
|
|
|
|
|
A. Ogawa, E. Mori, K. Minematsu, W. Taki, A. Takahashi, S. Nemoto, S. Miyamoto, M. Sasaki, T. Inoue, and for The MELT Japan Study Group Randomized Trial of Intraarterial Infusion of Urokinase Within 6 Hours of Middle Cerebral Artery Stroke: The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) Japan Stroke, October 1, 2007; 38(10): 2633 - 2639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-H. Rha and J. L. Saver Response to Letter by Kent and Mandava Stroke, October 1, 2007; 38(10): e104 - e104. [Full Text] [PDF]
|
|
|
|
|
|
J. De Keyser, Z. Gdovinova, M. Uyttenboogaart, P. C. Vroomen, and G. J. Luijckx Intravenous Alteplase for Stroke: Beyond the Guidelines and in Particular Clinical Situations Stroke, September 1, 2007; 38(9): 2612 - 2618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
The IMS II Trial Investigators The Interventional Management of Stroke (IMS) II Study Stroke, July 1, 2007; 38(7): 2127 - 2135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Mandava and T. A. Kent Intra-arterial therapies for acute ischemic stroke Neurology, June 12, 2007; 68(24): 2132 - 2139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Lindsberg and H. P. Mattle Response to Letter by Vatankhah et al Stroke, June 1, 2007; 38(6): e30 - e30. [Full Text] [PDF]
|
|
|
|
 |
|
 H. P. Adams Jr, G. del Zoppo, M. J. Alberts, D. L. Bhatt, L. Brass, A. Furlan, R. L. Grubb, R. T. Higashida, E. C. Jauch, C. Kidwell, et al. Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation, May 22, 2007; 115(20): e478 - e534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Mikulik, M. Ribo, M. D. Hill, J. C. Grotta, M. Malkoff, C. Molina, M. Rubiera, R. Delgado-Mederos, J. Alvarez-Sabin, A. V. Alexandrov, et al. Accuracy of Serial National Institutes of Health Stroke Scale Scores to Identify Artery Status in Acute Ischemic Stroke Circulation, May 22, 2007; 115(20): 2660 - 2665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. P. Adams Jr, G. del Zoppo, M. J. Alberts, D. L. Bhatt, L. Brass, A. Furlan, R. L. Grubb, R. T. Higashida, E. C. Jauch, C. Kidwell, et al. Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/ American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists Stroke, May 1, 2007; 38(5): 1655 - 1711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Saqqur, K. Uchino, A. M. Demchuk, C. A. Molina, Z. Garami, S. Calleja, N. Akhtar, F. O. Orouk, A. Salam, A. Shuaib, et al. Site of Arterial Occlusion Identified by Transcranial Doppler Predicts the Response to Intravenous Thrombolysis for Stroke Stroke, March 1, 2007; 38(3): 948 - 954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Khatri, L. R. Wechsler, and J. P. Broderick Intracranial Hemorrhage Associated With Revascularization Therapies Stroke, February 1, 2007; 38(2): 431 - 440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Shaltoni, K. C. Albright, N. R. Gonzales, R. U. Weir, A. M. Khaja, R. M. Sugg, M. S. Campbell III, E. D. Cacayorin, J. C. Grotta, and E. A. Noser Is Intra-Arterial Thrombolysis Safe After Full-Dose Intravenous Recombinant Tissue Plasminogen Activator for Acute Ischemic Stroke? Stroke, January 1, 2007; 38(1): 80 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Tomsick 2006: A Stroke Odyssey AJNR Am. J. Neuroradiol., November 1, 2006; 27(10): 2019 - 2021. [Full Text] [PDF]
|
|
|
|
|
|
L. Sekoranja, J. Loulidi, H. Yilmaz, K. Lovblad, P. Temperli, M. Comelli, and R. F. Sztajzel Intravenous Versus Combined (Intravenous and Intra-Arterial) Thrombolysis in Acute Ischemic Stroke: A Transcranial Color-Coded Duplex Sonography-Guided Pilot Study Stroke, July 1, 2006; 37(7): 1805 - 1809. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.S. Smith and for the Multi MERCI Investigators Safety of Mechanical Thrombectomy and Intravenous Tissue Plasminogen Activator in Acute Ischemic Stroke. Results of the Multi Mechanical Embolus Removal in Cerebral Ischemia (MERCI) Trial, Part I AJNR Am. J. Neuroradiol., June 1, 2006; 27(6): 1177 - 1182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-F.M. Fitzsimmons, T. Becske, and P.K. Nelson Rapid stent-supported revascularization in acute ischemic stroke. AJNR Am. J. Neuroradiol., May 1, 2006; 27(5): 1132 - 1134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-C. Shyu, S.-Z. Lin, C.-C. Lee, D. D. Liu, and H. Li Granulocyte colony-stimulating factor for acute ischemic stroke: a randomized controlled trial Can. Med. Assoc. J., March 28, 2006; 174(7): 927 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
The IMS Study Investigators Hemorrhage in the Interventional Management of Stroke Study Stroke, March 1, 2006; 37(3): 847 - 851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Choi, B. T. Bateman, S. Mangla, R. S. Marshall, S. Prabhakaran, J. Chong, J. P. Mohr, H. Mast, and J. Pile-Spellman Endovascular Recanalization Therapy in Acute Ischemic Stroke Stroke, February 1, 2006; 37(2): 419 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Part 9: Stroke Circulation, November 29, 2005; 112(22_suppl): III-110 - III-104. [Full Text] [PDF]
|
|
|
|
|
|
S. Mangiafico, M. Cellerini, P. Nencini, G. Gensini, and D. Inzitari Intravenous Glycoprotein IIb/IIIa Inhibitor (Tirofiban) followed by Intra-Arterial Urokinase and Mechanical Thrombolysis in Stroke AJNR Am. J. Neuroradiol., November 1, 2005; 26(10): 2595 - 2601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Fischer, M. Arnold, K. Nedeltchev, C. Brekenfeld, P. Ballinari, L. Remonda, G. Schroth, and H. P. Mattle NIHSS Score and Arteriographic Findings in Acute Ischemic Stroke Stroke, October 1, 2005; 36(10): 2121 - 2125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Renowden Interventional neuroradiology J. Neurol. Neurosurg. Psychiatry, September 1, 2005; 76(suppl_3): iii48 - iii63. [Full Text] [PDF]
|
|
|
|
|
|
O. C. Singer, F. Dvorak, R. du Mesnil de Rochemont, H. Lanfermann, M. Sitzer, and T. Neumann-Haefelin A Simple 3-Item Stroke Scale: Comparison With the National Institutes of Health Stroke Scale and Prediction of Middle Cerebral Artery Occlusion Stroke, April 1, 2005; 36(4): 773 - 776. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ergin and N. Ergin Is Thrombolytic Therapy Associated With Increased Mortality?: Meta-analysis of Randomized Controlled Trials Arch Neurol, March 1, 2005; 62(3): 362 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Slivka, G. A. Christoforidis, E. C. Bourekas, P. E. Calendine, and M. A. Notestine Clinical and Imaging Outcomes after Stroke with Normal Angiograms AJNR Am. J. Neuroradiol., February 1, 2005; 26(2): 242 - 245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Flaherty, D. Woo, B. Kissela, E. Jauch, A. Pancioli, J. Carrozzella, J. Spilker, P. Sekar, J. Broderick, and T. Tomsick Combined IV and intra-arterial thrombolysis for acute ischemic stroke Neurology, January 25, 2005; 64(2): 386 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Pierre Gobin, S. Starkman, G. R. Duckwiler, T. Grobelny, C. S. Kidwell, R. Jahan, J. Pile-Spellman, A. Segal, F. Vinuela, and J. L. Saver MERCI 1: A Phase 1 Study of Mechanical Embolus Removal in Cerebral Ischemia Stroke, December 1, 2004; 35(12): 2848 - 2854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Y. Lee, D. I. Kim, S. H. Kim, S. I. Lee, H. W. Chung, Y. W. Shim, S. M. Kim, and J. H. Heo Sequential Combination of Intravenous Recombinant Tissue Plasminogen Activator and Intra-Arterial Urokinase in Acute Ischemic Stroke AJNR Am. J. Neuroradiol., October 1, 2004; 25(9): 1470 - 1475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-K. Lee, D. I. Kim, S. Y. Kim, D. J. Kim, J. E. Lee, and J. H. Kim Reperfusion Cellular Injury in an Animal Model of Transient Ischemia AJNR Am. J. Neuroradiol., September 1, 2004; 25(8): 1342 - 1347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sorimachi, Y. Fujii, N. Tsuchiya, T. Nashimoto, A. Harada, Y. Ito, and R. Tanaka Recanalization by Mechanical Embolus Disruption during Intra-Arterial Thrombolysis in the Carotid Territory AJNR Am. J. Neuroradiol., September 1, 2004; 25(8): 1391 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Arnold, K Nedeltchev, G Schroth, R W Baumgartner, L Remonda, T J Loher, F Stepper, M Sturzenegger, B Schuknecht, and H P Mattle Clinical and radiological predictors of recanalisation and outcome of 40 patients with acute basilar artery occlusion treated with intra-arterial thrombolysis J. Neurol. Neurosurg. Psychiatry, June 1, 2004; 75(6): 857 - 862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
The IMS Study Investigators Combined Intravenous and Intra-Arterial Recanalization for Acute Ischemic Stroke: The Interventional Management of Stroke Study Stroke, April 1, 2004; 35(4): 904 - 911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nakajima, K. Kimura, T. Ogata, T. Takada, M. Uchino, and K. Minematsu Relationships between Angiographic Findings and National Institutes of Health Stroke Scale Score in Cases of Hyperacute Carotid Ischemic Stroke AJNR Am. J. Neuroradiol., February 1, 2004; 25(2): 238 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Provenzale, R. Jahan, T. P. Naidich, and A. J. Fox Assessment of the Patient with Hyperacute Stroke: Imaging and Therapy Radiology, November 1, 2003; 229(2): 347 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Jungreis, E. Nemoto, F. Boada, and M. B. Horowitz Model of Reversible Cerebral Ischemia in a Monkey Model AJNR Am. J. Neuroradiol., October 1, 2003; 24(9): 1834 - 1836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Hill, H. A. Rowley, F. Adler, M. Eliasziw, A. Furlan, R. T. Higashida, L. R. Wechsler, H. C. Roberts, W. P. Dillon, N. J. Fischbein, et al. Selection of Acute Ischemic Stroke Patients for Intra-Arterial Thrombolysis With Pro-Urokinase by Using ASPECTS Stroke, August 1, 2003; 34(8): 1925 - 1931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Higashida and A. J. Furlan Trial Design and Reporting Standards for Intra-Arterial Cerebral Thrombolysis for Acute Ischemic Stroke Stroke, August 1, 2003; 34 (8): e109 - e137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Hsia, H. S. Sachdev, J. Tomlinson, S. A. Hamilton, and D. C. Tong Efficacy of IV tissue plasminogen activator in acute stroke: Does stroke subtype really matter? Neurology, July 8, 2003; 61(1): 71 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hahnel, P. D. Schellinger, A. Gutschalk, K. Geletneky, M. Hartmann, M. Knauth, and K. Sartor Local Intra-arterial Fibrinolysis of Thromboemboli Occurring During Neuroendovascular Procedures With Recombinant Tissue Plasminogen Activator Stroke, July 1, 2003; 34(7): 1723 - 1728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Rymer, D. Thurtchley, and D. Summers Expanded Modes of Tissue Plasminogen Activator Delivery in a Comprehensive Stroke Center Increases Regional Acute Stroke Interventions Stroke, June 1, 2003; 34 (6): e58 - e60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Shih, J. L. Saver, J. R. Alger, S. Starkman, M. C. Leary, F. Vinuela, G. Duckwiler, Y. P. Gobin, R. Jahan, J. P. Villablanca, et al. Perfusion-Weighted Magnetic Resonance Imaging Thresholds Identifying Core, Irreversibly Infarcted Tissue Stroke, June 1, 2003; 34(6): 1425 - 1430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. P. Adams Jr, R. J. Adams, T. Brott, G. J. del Zoppo, A. Furlan, L. B. Goldstein, R. L. Grubb, R. Higashida, C. Kidwell, T. G. Kwiatkowski, et al. Guidelines for the Early Management of Patients With Ischemic Stroke: A Scientific Statement From the Stroke Council of the American Stroke Association Stroke, April 1, 2003; 34(4): 1056 - 1083. [Full Text] [PDF]
|
|
|
|
|
|
B. R. Mahon, G. M. Nesbit, S. L. Barnwell, W. Clark, T. R. Marotta, A. Weill, P. A. Teal, and A. I. Qureshi North American Clinical Experience with the EKOS MicroLysUS Infusion Catheter for the Treatment of Embolic Stroke AJNR Am. J. Neuroradiol., March 1, 2003; 24(3): 534 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C Foerch, R Du Mesnil de Rochemont, O Singer, T Neumann-Haefelin, M Buchkremer, F E Zanella, H Steinmetz, and M Sitzer S100B as a surrogate marker for successful clot lysis in hyperacute middle cerebral artery occlusion J. Neurol. Neurosurg. Psychiatry, March 1, 2003; 74(3): 322 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Labiche, F. Al-Senani, A. W. Wojner, J. C. Grotta, M. Malkoff, and A. V. Alexandrov Is the Benefit of Early Recanalization Sustained at 3 Months?: A Prospective Cohort Study Stroke, March 1, 2003; 34(3): 695 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Pelz Advances in Interventional Neuroradiology Stroke, February 1, 2003; 34(2): 357 - 358. [Full Text] [PDF]
|
|
|
|
|
|
P. D. Schellinger, J. B. Fiebach, W. Hacke, and J. Rother Imaging-Based Decision Making in Thrombolytic Therapy for Ischemic Stroke: Present Status Stroke, February 1, 2003; 34(2): 575 - 583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kassem-Moussa and C. Graffagnino Nonocclusion and Spontaneous Recanalization Rates in Acute Ischemic Stroke: A Review of Cerebral Angiography Studies Arch Neurol, December 1, 2002; 59(12): 1870 - 1873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Lisboa, B. D. Jovanovic, and M. J. Alberts Analysis of the Safety and Efficacy of Intra-Arterial Thrombolytic Therapy in Ischemic Stroke Stroke, December 1, 2002; 33(12): 2866 - 2871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|