Clinical trials in acute ischemic stroke

CNS Drugs

Volumn 28, Issue 10, 2014, Pages 929-938

  Kikuchi, Kiyoshi ^a,b   Tanaka, Eiichiro ^b   Murai, Yoshinaka ^b   Tancharoen, Salunya ^a  

^a MAHIDOL UNIVERSITY   (Thailand)

^b KURUME UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ALTEPLASE; DESMOTEPLASE; DEXAMETHASONE; DEXTRAN 40; DISUFENTON SODIUM; GINSENOSIDE RD; MAGNESIUM; MINOCYCLINE; NORPHENAZONE; PLACEBO; POSTSYNAPTIC DENSITY PROTEIN 95 INHIBITOR; PROTEIN INHIBITOR; TENECTEPLASE; UNCLASSIFIED DRUG; URIC ACID; NEUROPROTECTIVE AGENT;

BLOOD CLOT LYSIS; BRAIN HEMORRHAGE; BRAIN INJURY; BRAIN ISCHEMIA; CLINICAL TRIAL (TOPIC); CONTINUOUS INFUSION; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; EXCITOTOXICITY; FIBRINOLYTIC THERAPY; HUMAN; NEUROPROTECTION; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); RECOMMENDED DRUG DOSE; REVIEW; TREATMENT OUTCOME; ANIMAL; DRUG COMBINATION; ENDOVASCULAR SURGERY; MULTIMODALITY CANCER THERAPY; STROKE;

ANIMALS; BRAIN ISCHEMIA; CLINICAL TRIALS AS TOPIC; COMBINED MODALITY THERAPY; DRUG THERAPY, COMBINATION; ENDOVASCULAR PROCEDURES; HUMANS; NEUROPROTECTIVE AGENTS; STROKE;

EID: 84910154744     PISSN: 11727047     EISSN: 11791934     Source Type: Journal    
DOI: 10.1007/s40263-014-0199-6     Document Type: Review

References (91)

1. World Health Organization. The top 10 causes of death. http://www.who.int/mediacentre/factsheets/fs310/en/index.html. Accessed 3 Apr 2014.
2. Demaerschalk BM, Hwang HM, Leung G. US cost burden of ischemic stroke: a systematic literature review. Am J Manag Care. 2010;16:525-33.
3. Ingall T. Stroke: incidence, mortality, morbidity and risk. J Insur Med. 2004;36:143-52.
4. Amaro S, Chamorro A. Translational stroke research of the combination of thrombolysis and antioxidant therapy. Stroke. 2011;42:1495-9.
5. O'Collins VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, Howells DW. 1,026 experimental treatments in acute stroke. Ann Neurol. 2006;59:467-77.
6. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581-8.
7. Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, et al., for the ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008; 359:1317-29.
8. Wahlgren N, Ahmed N, Davalos A, Ford GA, Grond M, Hacke W, et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet. 2007;369:275-82.
9. Lapchak PA. Recommendations and practices to optimize stroke therapy: developing effective translational research programs. Stroke. 2013;44:841-3.
10. Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Multicentre Acute Stroke Trial-Italy (MAST-I) Group. Lancet. 1995; 346:1509-14.
11. Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA. 1995;274:1017-25.
12. Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet. 1998;352:1245-51.
13. The IST-3 collaborative group, Sandercock P, Wardlaw JM, Lindley RI, Dennis M, Cohen G, et al. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the Third International Stroke Trial [IST-3]): a randomised controlled trial Lancet. 2012;379:2352-63.
14. Thrombolytic therapy with streptokinase in acute ischemic stroke. The Multicenter Acute Stroke Trial-Europe Study Group. N Engl J Med. 1996; 335:145-50
15. Donnan GA, Davis SM, Chambers BR, Gates PC, Hankey GJ, McNeil JJ, Rosen D, Stewart-Wynne EG, Tuck RR. Streptokinase for acute ischemic stroke with relationship to time of administration: Australian Streptokinase (ASK) Trial Study Group. JAMA. 1996;276:961-6.
16. Clark WM, Albers GW, Madden KP, Hamilton S. The rtPA (alteplase) 0- to 6-hour acute stroke trial, part A (A0276g): results of a double-blind, placebo-controlled, multicenter study. Thrombolytic Therapy in Acute Ischemic Stroke Study Investigators. Stroke. 2000;31:811-6.
17. Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, Hamilton S. Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA. 1999;282:2019-26.
18. Saver JL, Fonarow GC, Smith EE, Reeves MJ, Grau-Sepulveda MV, Pan W, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA. 2013;309:2480-8.
19. Lees KR, Bluhmki E, von Kummer R, Brott TG, Toni D, Grotta JC, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet. 2010;375:1695-703.
20. Meretoja A, Keshtkaran M, Saver JL, Tatlisumak T, Parsons MW, Kaste M, et al. Stroke thrombolysis: save a minute, save a day. Stroke. 2014;45:1053-8.
21. Helsinki Stroke Thrombolysis Registry Group. Does time of the day or physician experience affect outcome of acute ischemic stroke patients treated with thrombolysis? Int J Stroke. 2012;7:511-6.
22. Fonarow GC, Smith EE, Saver JL, Reeves MJ, Bhatt DL, Grau-Sepulveda MV et al. Timeliness of tissue-type plasminogen activator therapy in acute ischemic stroke: patient characteristics, hospital factors, and outcomes associated with door-to-needle times within 60 minutes. Circulation. 2011;123:750-758.
23. Albers GW, Olivot JM. Intravenous alteplase for ischaemic stroke. Lancet. 2007;369:249-50.
24. Fang MC, Cutler DM, Rosen AB. Trends in thrombolytic use for ischemic stroke in the United States. J Hosp Med. 2010;5:406-9.
25. Katzan IL, Hammer MD, Hixson ED, Furlan AJ, Abou-Chebl A, Nadzam DM. Utilization of intravenous tissue plasminogen activator for acute ischemic stroke. Arch Neurol. 2004;61:346-50.
26. Lichtman JH, Watanabe E, Allen NB, Jones SB, Dostal J, Goldstein LB. Hospital arrival time and intravenous t-PA use in US Academic Medical Centers, 2001-2004. Stroke. 2009;40:3845-50.
27. Wahlgren N, Ahmed N, Davalos A, Hacke W, Millán M, Muir K, et al. Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet. 2008;372:1303-9.
28. Sandercock P, Wardlaw JM, Lindley RI, Dennis M, Cohen G, Murray G, et al. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the Third International Stroke Trial [IST-3]): a randomised controlled trial. Lancet. 2012;379:2352-63.
29. Wardlaw JM, Murray V, Berge E, del Zoppo G, Sandercock P, Lindley RL, et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet. 2012;379:2364-72.
30. The Internet Stroke Center: Extending the Time for Thrombolysis in Emergency Neurological Deficits "EXTEND." http://www.strokecenter.org/trials/clinicalstudies/extending-the-time-for-thrombolysis-in-emergency-neurological-deficit. Accessed 3 Apr 2014.
31. Boudreau DM, Guzauskas G, Villa KF, Fagan SC, Veenstra DL. A model of cost-effectiveness of tissue plasminogen activator in patient subgroups 3 to 4.5 hours after onset of acute ischemic stroke. Ann Emerg Med. 2013;61:46-55.
32. Lee KY, Han SW, Kim SH, Nam HS, Ahn SW, Kim DJ, et al. Early recanalization after intravenous administration of recombinant tissue plasminogen activator as assessed by pre- and post-thrombolytic angiography in acute ischemic stroke patients. Stroke. 2007;38:192-3.
33. Saqqur M, Tsivgoulis G, Molina CA, et al. Symptomatic intracerebral hemorrhage and recanalization after IV rt-PA: a multicenter study. Neurology. 2008;71:1304-12.
34. Saqqur M, Uchino K, Demchuk AM, Molina CA, Garami Z, Calleja S, et al. Site of arterial occlusion identified by transcranial Doppler predicts the response to intravenous thrombolysis for stroke. Stroke. 2007;38:948-54.
35. Lo EH, Dalkara T, Moskowitz MA. Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci. 2003;4:399-415.
36. Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999;22:391-7.
37. Lapchak PA, Schubert DR, Maher PA. Delayed treatment with a novel neurotrophic compound reduces behavioral deficits in rabbit ischemic stroke. J Neurochem. 2011;116:122-31.
38. Kaste M, Fogelholm R, Waltimo O. Combined dexamethasone and low-molecular-weight dextran in acute brain infarction: double-blind study. Br Med J. 1976;2:1409-10.
39. Minnerup J, Sutherland BA, Buchan AM, Kleinschnitz C. Neuroprotection for stroke: current status and future perspectives. Int J Mol Sci. 2012;13:11753-72.
40. Piironen K, Tiainen M, Mustanoja S, Kaukonen KM, Meretoja A, Tatlisumak T, et al. Mild hypothermia after intravenous thrombolysis in patients with acute stroke: a randomized controlled trial. Stroke. 2014;45:486-91.
41. Barreto AD, Alexandrov AV, Shen L, Sisson A, Bursaw AW, Sahota P, et al. Device in patients with acute ischemic stroke CLOTBUST-hands free: pilot safety study of a novel operator-independent ultrasound. Stroke. 2013;44:3376-81.
42. Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD, et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013;368:893-903.
43. Ciccone A, Valvassori L, Nichelatti M, Sgoifo A, Ponzio M, Sterzi R. Endovascular treatment for acute ischemic stroke. N Engl J Med. 2013;368:904-13.
44. Kidwell CS, Jahan R, Gornbein J, Alger JR, Nenov V, Ajani Z, et al. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med. 2013;368:914-23.
45. Smith WS, Sung G, Starkman S, Saver JL, Kidwell CS, Gobin YP, et al. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke. 2005;36:1432-8.
46. Broussalis E, Trinka E, Hitzl W, Wallner A, Chroust V, Killer-Oberpfalzer M. Comparison of stent-retriever devices versus the Merci retriever for endovascular treatment of acute stroke. Am J Neuroradiol. 2013;34:366-72.
47. Schaar KL, Brenneman MM, Savitz SI. Functional assessments in the rodent stroke model. Exp Transl Stroke Med. 2010;19:1-11.
48. Stroke Therapy Academic Industry Roundtable (STAIR). Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke. 1999;30:2752-8.
49. Lees KR, Zivin JA, Ashwood T, Davalos A, Davis SM, Diener H. NXY-059 for acute ischemic stroke. N Engl J Med. 2006;354:588-600.
50. Shuaib A, Lees KR, Lyden P, Grotta J, Davalos A, Davis SM. NXY-059 for the treatment of acute ischemic stroke. N Engl J Med. 2007;357:562-71.
51. Savitz SI. A critical appraisal of the NXY-059 neuroprotection studies for acute stroke: a need for more rigorous testing of neuroprotective agents in animal models of stroke. Exp Neurol. 2007;205:20-5.
52. Kuroda S, Tsuchidate R, Smith ML, Maples KR, Siesjo BK. Neuroprotective effects of a novel nitrone, NXY-059, after transient focal cerebral ischemia in the rat. J Cereb Blood Flow Metab. 1999;19:778-87.
53. Liu X, Xia J, Wang L, Song Y, Yang J, Yan Y, et al. Efficacy and safety of ginsenoside-Rd for acute ischemic stroke: a randomized, double-blind, placebo-controlled, phase II multicenter trial. Eur J Neurol. 2009;16:569-75.
54. Liu X, Wang L, Wen A, Yang J, Yan Y, Song Y, et al. Ginsenoside-Rd improves outcome of acute ischaemic stroke: a randomized, double-blind, placebo-controlled, multicenter trial. Eur J Neurol. 2012;19:855-63.
55. Bogousslavsky J, Regli F, Zumstein V, Köbberling W. Double-blind study of nimodipine in non-severe stroke. Eur Neurol. 1990;30:23-6.
56. Hill MD, Martin RH, Mikulis D, Wong JH, Silver FL, Terbrugge KG. Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT): a phase 2, randomized, double-blind, placebo-controlled trial. Lancet Neurol. 2012;11:942-50.
57. Kikuchi K, Miura N, Kawahara KI, Murai Y, Morioka M, Lapchak PA, et al. Edaravone (Radicut), a free radical scavenger, is a potentially useful addition to thrombolytic therapy in patients with acute ischemic stroke. Biomed Rep. 2013;1:7-12.
58. Kikuchi K, Tancharoen S, Matsuda F, Biswas KK, Ito T, Morimoto Y, et al. Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4. Biochem Biophys Res Commun. 2009;390:1121-5.
59. Tanaka E, Niiyama S, Sato S, Yamada A, Higashi H. Arachidonic acid metabolites contribute to the irreversible depolarization induced by in vitro ischemia. J Neurophysiol. 2003;90:3213-23.
60. Yagi K, Kitazato KT, Uno M, Tada Y, Kinouchi T, Shimada K, et al. Edaravone, a free radical scavenger, inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator. Stroke. 2009;40:626-31.
61. Yamashita T, Kamiya T, Deguchi K, Inaba T, Zhang H, Shang J, et al. Dissociation and protection of the neurovascular unit after thrombolysis and reperfusion in ischemic rat brain. J Cereb Blood Flow Metab. 2009;29:715-25.
62. Kaste M, Murayama S, Ford GA, Dippel DW, Walters MR, Tatlisumak T. Safety, tolerability and pharmacokinetics of MCI-186 in patients with acute ischemic stroke: new formulation and dosing regimen. Cerebrovasc Dis. 2013;36:196-204.
63. Nakagawara J, Minematsu K, Okada Y, Tanahashi N, Nagahiro S, Mori E. Thrombolysis with 0.6 mg/kg intravenous alteplase for acute ischemic stroke in routine clinical practice: the Japan post-Marketing Alteplase Registration Study (J-MARS). Stroke. 2010;41:1984-9.
64. Kimura K, Aoki J, Sakamoto Y, Kobayashi K, Sakai K, Inoue T, et al. Administration of edaravone, a free radical scavenger, during t-PA infusion can enhance early recanalization in acute stroke patients: a preliminary study. J Neurol Sci. 2012;313:132-6.
65. Watanabe T, Tahara M, Todo S. The novel antioxidant edaravone: from bench to bedside. Cardiovasc Ther. 2008;26:101-14.
66. Yoshida H, Yanai H, Namiki Y, Fukatsu-Sasaki K, Furutani N, Tada N. Neuroprotective effects of edaravone: a novel free radical scavenger in cerebrovascular injury. CNS Drug Rev. 2006;12:9-20.
67. UMIN CTR: Post-marketing Registry On Treatment with Edaravone in acute Cerebral infarction by the Time window of 4.5 hours. http://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000010785&language=J [in Japanese]. Accessed 3 Apr 2014.
68. UMIN CTR: Tissue type plasminogen activator (t-PA) and Edaravon combination therapy study. http://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000007504&language=J [in Japanese]. Accessed 3 Apr 2014.
69. Fagan SC, Waller JL, Nichols FT, Edwards DJ, Pettigrew LC, Clark WM, et al. Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study. Stroke. 2010;41:2283-7.
70. Kohler E, Prentice DA, Bates TR, Hankey GJ, Claxton A, van Heerden J, et al. Intravenous minocycline in acute stroke: a randomized, controlled pilot study and meta-analysis. Stroke. 2013;44:2493-9.
71. Blacker DJ, Prentice D, Alvaro A, Bates TR, Bynevelt M, Kelly A, et al. Reducing haemorrhagic transformation after thrombolysis for stroke: a strategy utilising minocycline. Stroke Res Treat. 2013;2013;362961.
72. Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology. 2007;69:1404-10.
73. Padma Srivastava MV, Bhasin A, Bhatia R, Garg A, Gaikwad S, Prasad K, et al. Efficacy of minocycline in acute ischemic stroke: a single-blinded, placebo-controlled trial. Neurol India. 2012;60:23-8.
74. Amaro S, Castellanos M, Segura T, Arenillas J, Martí-Fábregas J, Gállego J, et al.; URICO-ICTUS Investigators. The URICO-ICTUS Study: a randomized trial of efficacy and safety of uric acid administration in acute stroke. http://www.my.americanheart.org/idc/groups/ahamah-public/@wcm/@sop/@scon/documents/downloadable/ucm-460525.pdf. Accessed 3 Apr 2014.
75. The Medical News: FAST-MAG clinical trial finds that magnesium does not improve stroke-related disability. http://www.news-medical.net/news/20140214/FAST-MAG-clinical-trial-finds-that-magnesium-does-not-improve-stroke-related-disability.aspx. Accessed 3 Apr 2014.
76. FAST-MAG: scientific background. http://www.fastmag.info/sci-bkg.htm. Accessed 3 Apr 2014.
77. The Internet Stroke Center. Randomized Controlled Trial of Argatroban With tPA for Acute Stroke "ARTSS-2." http://www.strokecenter.org/trials/clinicalstudies/randomized-controlled-trial-of-argatroban-with-tpa-for-acute-stroke. Accessed 3 Apr 2014.
78. Pancioli AM, Adeoye O, Schmit PA, Khoury J, Levine SR, Tomsick TA, et al. CLEAR-ER Investigators. Combined approach to lysis utilizing eptifibatide and recombinant tissue plasminogen activator in acute ischemic stroke-enhanced regimen stroke trial. Stroke. 2013;44:2381-7.
79. The Internet Stroke Center. Thrombolysis and Deferoxamine in Middle Cerebral Artery Occlusion "TANDEM-1." http://www.strokecenter.org/trials/clinicalstudies/thrombolysis-and-deferoxamine-in-middle-cerebral-artery-occlusion. Accessed 3 Apr 2014.
80. Tanswell P, Modi N, Combs D, Danays T. Pharmacokinetics and pharmacodynamics of tenecteplase in fibrinolytic therapy of acute myocardial infarction. Clin Pharmacokinet. 2002;41:1229-45.
81. Verstraete M. Third-generation thrombolytic drugs. Am J Med. 2000;109:52-8.
82. Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F, et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med. 2012;366:1099-107.
83. Liberatore GT, Samson A, Bladin C, Schleuning WD, Medcalf RL. Vampire bat salivary plasminogen activator (desmoteplase): a unique fibrinolytic enzyme that does not promote neurodegeneration. Stroke. 2003;34:537-43.
84. Schleuning WD. Vampire bat plasminogen activator DSPA-alpha-1 (desmoteplase): a thrombolytic drug optimized by natural selection. Haemostasis. 2001;31:118-22.
85. Hacke W, Albers G, Al-Rawi Y, Bogousslavsky J, Davalos A, Eliasziw M, et al. The Desmoteplase in Acute Ischemic Stroke Trial (DIAS): a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. Stroke. 2005;36:66-73.
86. Furlan AJ, Eyding D, Albers GW, Al-Rawi Y, Lees KR, Rowley HA. Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset. Stroke. 2006;37:1227-31.
87. Hacke W, Furlan AJ, Al-Rawi Y, Davalos A, Fiebach JB, Gruber F, et al. Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2009;8:141-50.
88. The Internet Stroke Center. Efficacy and safety study of Desmoteplase to Treat Acute Ischemic Stroke (DIAS-4). http://www.strokecenter.org/trials/clinicalstudies/efficacy-and-safety-study-of-desmoteplase-to-treat-acute-ischemic-stroke-dias-4. Accessed 3 Apr 2014.
89. The Internet Stroke Center. Efficacy and safety study of Desmoteplase to Treat Acute Ischemic Stroke "DIAS-3." http://www.strokecenter.org/trials/clinicalstudies/efficacy-and-safety-study-of-desmoteplase-to-treat-acute-ischemic-stroke. Accessed 3 Apr 2014.
90. Paciaroni M, Medeiros E, Bogousslavsky J. Desmoteplase. Expert Opin Biol Ther. 2009;9:773-8.
91. Jones CW, Handler L, Crowell KE, Keil LG, Weaver MA, Platts-Mills TF. Non-publication of large randomized clinical trials: cross sectional analysis. BMJ. 2013;347:f6104.