A pilot dose-escalation safety study of tenecteplase in acute ischemic stroke

被引:167
作者
Haley, EC
Lyden, PD
Johnston, KC
Hemmen, TM
机构
[1] Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA 22908 USA
[2] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA
关键词
ischemic stroke; tenecteplase; tissue plasminogen activator; thrombolytic therapy;
D O I
10.1161/01.STR.0000154872.73240.e9
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Purpose-Recombinant tissue-type plasminogen activator (rtPA) is the only approved treatment in acute ischemic stroke. However, intracerebral hemorrhage (ICH) occurs in 6.4% of patients treated with rtPA and limits its use. Tenecteplase (TNK) is a modified form of rtPA, with longer half-life and greater fibrin specificity. Patients after myocardial infarction had fewer systemic hemorrhages when treated with TNK compared with rtPA. This open-label, dose-escalation safety study was conducted to develop initial experience with TNK in the treatment of ischemic stroke. Methods-Eligible patients were treated with an intravenous bolus infusion of TNK within 3 hours of stroke onset. The dose escalation was conducted in tiers of 25 patients, starting at 0.1 mg/kg, to a planned maximum of 0.6 mg/kg. The primary endpoint was symptomatic intracranial hemorrhage within 36 hours of treatment. All patients were followed-up for 3 months. Results-Eighty-eight (88) patients were treated in 4 dosing tiers. In the first 3 tiers (0.1, 0.2, 0.4 mg/kg) of 25 patients each, no symptomatic and 2 (8%), 8 (32%), and 7 (28%) asymptomatic ICHs occurred. Enrollment into the fourth tier at 0.5 mg/kg was closed after 2 of 13 patients (15%) had symptomatic and 3 (23%) had asymptomatic ICHs. Overall, modified Rankin scores at 3 months were similar to those of historical controls treated with rtPA and not significantly different between treatment groups. Conclusions-TNK doses of 0.1 to 0.4 mg/kg are safe in ischemic stroke. Future trials are needed to compare the effect of TNK on neurological outcome and safety as compared with rtPA.
引用
收藏
页码:607 / 612
页数:6
相关论文
共 19 条
[1]   CLASSIFICATION OF SUBTYPE OF ACUTE ISCHEMIC STROKE - DEFINITIONS FOR USE IN A MULTICENTER CLINICAL-TRIAL [J].
ADAMS, HP ;
BENDIXEN, BH ;
KAPPELLE, LJ ;
BILLER, J ;
LOVE, BB ;
GORDON, DL ;
MARSH, EE ;
KASE, CS ;
WOLF, PA ;
BABIKIAN, VL ;
LICATAGEHR, EE ;
ALLEN, N ;
BRASS, LM ;
FAYAD, PB ;
PAVALKIS, FJ ;
WEINBERGER, JM ;
TUHRIM, S ;
RUDOLPH, SH ;
HOROWITZ, DR ;
BITTON, A ;
MOHR, JP ;
SACCO, RL ;
CLAVIJO, M ;
ROSENBAUM, DM ;
SPARR, SA ;
KATZ, P ;
KLONOWSKI, E ;
CULEBRAS, A ;
CAREY, G ;
MARTIR, NI ;
FICARRA, C ;
HOGAN, EL ;
CARTER, T ;
GURECKI, P ;
MUNTZ, BK ;
RAMIREZLASSEPAS, M ;
TULLOCH, JW ;
QUINONES, MR ;
MENDEZ, M ;
ZHANG, SM ;
ALA, T ;
JOHNSTON, KC ;
ANDERSON, DC ;
TARREL, RM ;
NANCE, MA ;
BUDLIE, SR ;
DIERICH, M ;
HELGASON, CM ;
HIER, DB ;
SHAPIRO, RA .
STROKE, 1993, 24 (01) :35-41
[2]  
*AM AC EM MED WORK, POS STAT AM AC EM M
[3]   A systems approach to immediate evaluation and management of hyperacute stroke - Experience at eight centers and implications for community practice and patient care [J].
Brott, T ;
Broderick, J ;
Kothari, R ;
ODonoghue, M ;
Barsan, W ;
Tomsick, T ;
Spilker, J ;
Miller, R ;
Sauerbeck, L ;
Farrell, J ;
Kelly, J ;
Perkins, T ;
McDonald, T ;
Rorick, M ;
Hickey, C ;
Armitage, J ;
Perry, C ;
Thalinger, K ;
Rhude, R ;
Schill, J ;
Becker, PS ;
Heath, RS ;
Adams, D ;
Reed, R ;
Klei, M ;
Hughes, A ;
Anthony, J ;
Baudendistel, D ;
Zadicoff, C ;
Rymer, M ;
Bettinger, I ;
Laubinger, P ;
Schmerler, M ;
Meiros, G ;
Lyden, P ;
Dunford, J ;
Zivin, J ;
Rapp, K ;
Babcock, T ;
Daum, P ;
Persona, D ;
Brody, M ;
Jackson, C ;
Lewis, S ;
Liss, J ;
Mahdavi, Z ;
Rothrock, J ;
Tom, T ;
Zweifler, R ;
Kobayashi, J .
STROKE, 1997, 28 (08) :1530-1540
[4]   Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke [J].
Brott, T ;
Broderick, J ;
Kothari, R ;
ODonoghue, M ;
Barsan, W ;
Tomsick, T ;
Spilker, J ;
Miller, R ;
Sauerbeck, L ;
Farrell, J ;
Kelly, J ;
Perkins, T ;
Miller, R ;
McDonald, T ;
Rorick, M ;
Hickey, C ;
Armitage, J ;
Perry, C ;
Thalinger, K ;
Rhude, R ;
Schill, J ;
Becker, PS ;
Heath, RS ;
Adams, D ;
Reed, R ;
Klei, M ;
Hughes, A ;
Anthony, J ;
Baudendistel, D ;
Zadicoff, C ;
Rymer, M ;
Bettinger, I ;
Laubinger, P ;
Schmerler, M ;
Meiros, G ;
Lyden, P ;
Dunford, J ;
Zivin, J ;
Rapp, K ;
Babcock, T ;
Daum, P ;
Persona, D ;
Brody, M ;
Jackson, C ;
Lewis, S ;
Liss, J ;
Mahdavi, Z ;
Rothrock, J ;
Tom, T ;
Zweifler, R .
STROKE, 1997, 28 (11) :2109-2118
[5]   Predicting major neurological improvement with intravenous recombinant tissue plasminogen activator treatment of stroke [J].
Brown, DL ;
Johnston, KC ;
Wagner, DP ;
Haley, EC .
STROKE, 2004, 35 (01) :147-150
[6]   TNK tissue plasminogen activator compared with front-loaded alteplase in acute myocardial infarction - Results of the TIMI 10B trial [J].
Cannon, CP ;
Gibson, CM ;
McCabe, CH ;
Adgey, AAJ ;
Schweiger, MJ ;
Sequeira, RF ;
Grollier, G ;
Giugliano, RP ;
Frey, M ;
Mueller, HS ;
Steingart, RM ;
Weaver, WD ;
Van de Werf, F ;
Braunwald, E .
CIRCULATION, 1998, 98 (25) :2805-2814
[7]   Comparison of TNK with wild-type tissue plasminogen activator in a rabbit embolic stroke model [J].
Chapman, DF ;
Lyden, P ;
Lapchak, PA ;
Nunez, S ;
Thibodeaux, H ;
Zivin, J .
STROKE, 2001, 32 (03) :748-752
[8]  
HACKE W, 1995, JAMA-J AM MED ASSOC, V274, P1017, DOI 10.1001/jama.274.13.1017
[9]   HEMORRHAGIC CEREBRAL INFARCTION - A PROSPECTIVE-STUDY [J].
HORNIG, CR ;
DORNDORF, W ;
AGNOLI, AL .
STROKE, 1986, 17 (02) :179-185
[10]   Medical and neurological complications of ischemic stroke - Experience from the RANTTAS trial [J].
Johnston, KC ;
Li, JY ;
Lyden, PD ;
Hanson, SK ;
Feasby, TE ;
Adams, RJ ;
Faught, RE ;
Haley, EC .
STROKE, 1998, 29 (02) :447-453