Feigin VL, Lawes CMM, Bennett DA,
Anderson CS (2003) Stroke epidemiology:
a review of population-based
studies of the incidence, prevalence,
and case-fatality in the late 20th century.
Lancet Neurol 2:43–53
Article
PubMed
Google Scholar
Martinez-Vila E, Sieira PI (2001) Current
status and perspectives of neuroprotection
in ischemic stroke treatment.
Cerebrovasc Dis 11(Suppl 1):60–70
Article
PubMed
Google Scholar
Lees KR (2002) Management of acute
stroke. Lancet Neurol 1:41–50
Article
PubMed
Google Scholar
Fang J, Alderman MH (2001) Trend of
stroke hospitalization, United States,
1988–1997. Stroke 32:2221–2226
PubMed
Google Scholar
Howard G, Howard VJ, Katholi C, Oli
MK, Huston S (2001) Decline in US
stroke mortality: an analysis of temporal
patterns by sex, race, and geographic
region. Stroke 32:2213–2220
PubMed
Google Scholar
Michaud CM, Murray CJ, Bloom BR
(2001) Burden of disease–implications
for future research. JAMA 285:535–539
Article
PubMed
Google Scholar
Fisher M, Schaebitz W (2000) An
overview of acute stroke therapy: past,
present, and future. Arch Intern Med
160:3196–3206
Article
PubMed
Google Scholar
Caplan LR (2002) Treatment of patients
with stroke. Arch Neurol 59:703–707
Article
PubMed
Google Scholar
Heuschmann PU, Berger K, Misselwitz
B, Hermanek P, Leffmann C,Adelmann
M, Buecker-Nott HJ, Rother J,Neundoerfer
B,Kolominsky-Rabas PL
(2003) Frequency of thrombolytic
therapy in patients with acute ischemic
stroke and the risk of in-hospital
mortality. The German Stroke
Registers Study Group. Stroke 34:1106–1113
Article
Google Scholar
Muir KW, Grosset DG (1999) Neuroprotection
for acute stroke: making
clinical trials work. Stroke 30:180–182
PubMed
Google Scholar
Szoeke CE, Parsons MW, Butcher KS,
Baird TA, Mitchell PJ, Fox SE, Davis SM
(2003) Acute stroke thrombolysis with
intravenous tissue plasminogen activator
in an Australian tertiary hospital.
Med J Aust 178:324–328
PubMed
Google Scholar
Albers GW, Goldstein LB, Hall D, Lesko
LM, for the Aptiganel Acute Stroke
Investigators (2001) Aptiganel in acute
ischemic stroke. A randomized controlled
trial. JAMA 286:2673–2678
Article
PubMed
Google Scholar
Jensen BS (2002) BMS-204352: a potassium
channel opener developed for the
treatment of stroke. CNS Drug Reviews
8:353–360
PubMed
Google Scholar
Davis SM, Lees KR, Albers GW, Diener
HC, Markabi S, Karlsson G, et al. (2000)
Selfotel in acute ischemic stroke: possible
neurotoxic effects of an NMDA
antagonist. Stroke 31:347–354
PubMed
Google Scholar
Davalos A, Castillo J, Alvarez-Sabin J,
Secades JJ, Mercadal J, Lopez S, et al.
(2002) Oral citicoline in acute ischemic
stroke: an individual patient data pooling
analysis of clinical trials. Stroke
33:2850–2857
Article
PubMed
Google Scholar
Clark WM, Williams BJ, Selzer KA,
Zweifler RM, Sabounjian LA, Gammans
RE (1999) A randomized efficacy
trial of citicoline in patients with acute
ischemic stroke. Stroke 30:2592–2597
PubMed
Google Scholar
Clark WM, Wechsler LR, Sabounjian
LA, Schwiderski UE (2001) A phase III
randomized efficacy trial of 2000 mg
citicoline in acute ischemic stroke patients.
Neurology 57:1595–1602
PubMed
Google Scholar
Wahlgren NG, Ranasinha KW, Rosolacci
T, et al. (1999) Clomethiazole
Acute Stroke Study (CLASS). Results of
a randomized, controlled trial of
clomethiazole versus placebo in 1360
acute stroke patients. Stroke 30:21–28
PubMed
Google Scholar
Lyden P, Shuaib A, Ng K, Levin K, et al.
(2002) Clomethiazole Acute Stroke
Study in Ischemic Stroke (CLASS-I).
Final results. Stroke 33:122–129
Article
PubMed
Google Scholar
Yamaguchi T, Sano K, Takakura K,
Saito I, Shinohara Y, Asano T, et al.
(1998) Ebselen in acute ischemic
stroke: a placebo-controlled, doubleblind
clinical trial. Ebselen Study
Group. Stroke 29:12–17
PubMed
Google Scholar
Enlimomab Acute Stroke Trial Investigators
(2001) Use of anti-ICAM-1 therapy
in ischemic stroke: results of the
Enlimomab Acute Stroke Trial. Neurology
57:1428–1434
PubMed
Google Scholar
Lees KR, Asplund K, Carolei A, Davis
SM, Diener H-C, Kaste M, Orgogozo
J-M, Whitehead J, for the GAIN International
Investigators (2000) Glycine
antagonist (gavestinel) in neuroprotection
(GAIN International) in patients
with acute stroke: a randomised controlled
trial. Lancet 355:1949–1950
Article
PubMed
Google Scholar
Sacco RL, DeRosa JT,Haley EC Jr,
Levin B, Ordronneau P, Phillips SJ, et al.
(2001) Glycine antagonist in neuroprotection
for patients with acute stroke:
GAIN Americas: a randomized controlled
trial. JAMA 285:1719–1728
Article
PubMed
Google Scholar
Diener HC (1998) Multinational randomized
trial of lubeluzole in acute
ischaemic stroke: European and Australian
Lubeluzole Ischaemic Stroke
Study Group. Cerebrovasc Dis 8:172–181
Article
PubMed
Google Scholar
Diener HC, Cortens M, Ford G, et al.
(2000) Lubeluzole in acute ischemic
stroke treatment a double-blind study
with an 8-hour inclusion window comparing
a 10-mg daily dose of lubeluzole
with placebo. Stroke 31:2543–2551
PubMed
Google Scholar
Grotta J (1997) Lubeluzole treatment
of acute ischemic stroke. The US and
Canadian Lubeluzole Ischemic Stroke
Study Group. Stroke 28:2338–2346
PubMed
Google Scholar
Clark W, Ertag W, Orecchio E, Raps E
(1999) Cervene in acute ischemic
stroke: Results of a double-blind,
placebo-controlled, dose-comparison
study. J Stroke Cerebrovasc Dis 8:224–230
Google Scholar
Clark WM, Raps EC, Tong DC, Kelly
RE, for the Cervene Stroke Study
Investigators (2000) Cervene (nalmefene)
in acute ischemic stroke. Final
results of a phase III efficacy study.
Stroke 31:1234–1239
PubMed
Google Scholar
De Deyn PP, De Reuck J, Deberdt W,
Vlietinck R, Orgogozo JM, for the
Members of the Piracetam in Acute
Stroke Study (PASS) Group (1997)
Treatment of acute ischemic stroke
with piracetam. Stroke 28:2347–2352
PubMed
Google Scholar
Tirilazad mesylate in acute ischemic
stroke: A systematic review (2000)
Tirilazad International Steering
Committee. Stroke 31:2257–2265
PubMed
Google Scholar
Bogousslavsky J, Victor SJ, Salinas EO,
Pallay A, Donnan GA, Fieschi C, et al.
(2002) Fiblast (trafermin) in acute
stroke: results of the European-Australian
phase II/III safety and efficacy
trial. Cerebrovasc Dis 14:239–251
Article
PubMed
Google Scholar
http://www.dendron.com
Stroke Therapy Academic Industry
Roundtable II (STAIR-II) (2001) Recommendations
for clinical trial evaluation
of acute stroke therapies. Stroke
32:1598–1606
PubMed
Google Scholar
Gladstone DJ, Black SE, Hakim AM
(2002) Toward wisdom from failure:
lessons from neuroprotective stroke
trials and new therapeutic directions.
Stroke 33:2123–2136
Article
PubMed
Google Scholar
Grotta J (2002) Neuroprotection is
unlikely to be effective in humans
using current trial designs. Stroke
33:306–307
PubMed
Google Scholar
Lees KR, Hankey GJ, Hacke W (2003)
Design of future acute-stroke treatment
trials. Lancet Neurol 2:54–61
Article
PubMed
Google Scholar
Stroke Therapy Academic Industry
Roundtable (STAIR) (1998) Recommendations
for standards regarding
preclinical neuroprotective and
restorative drug development. Stroke
30:2752–2758
Google Scholar
Ikonomidou C, Turski L (2002) Why
did NMDA receptor antagonists fail
clinical trials for stroke and traumatic
brain injury? Lancet Neurol 1:383–386
PubMed
Google Scholar
Muir KW (2002) Heterogeneity of
stroke pathophysiology and neuroprotective
clinical trial design. Stroke
33:1545–1550
Article
PubMed
Google Scholar
Uchino K, Billheimer D, Cramer SC
(2001) Entry criteria and baseline
characteristics predict outcome in
acute stroke trials. Stroke 32:909–916
PubMed
Google Scholar
Yam PS, Dunn LT, Graham DI, Dewar
D, McCulloch JNMD (2000) A receptor
blockade fails to alter axonal injury in
focal cerebral ischemia. J Cereb Blood
Flow Metab 20:772–779
PubMed
Google Scholar
Bamford J, Sandercock P, Dennis M,
Burn J, Warlow C (1991) Classification
and natural history of clinically identifiable
subtypes of cerebral infarction.
Lancet 337:1521–1526
Article
PubMed
Google Scholar
Jorgensen HS, Reith J, Nakayama H,
Kammersgaard LP, Raaschou HO,
Olsen TS (1999) What determines
good recovery in patients with the
most severe strokes? The Copenhagen
Stroke Study. Stroke 30:2008–2012
PubMed
Google Scholar
Sherman DG, Atkinson RP, Chippendale
T, Levin KA, Ng K, Futrell N, et al.
(2000) Intravenous ancrod for treatment
of acute ischemic stroke: the
STAT study: a randomized controlled
trial. Stroke Treatment with Ancrod
Trial. JAMA 283:2395–2403
Article
PubMed
Google Scholar
Wahlgren NG, Bornhov S, Sharma A,
Cederin B, Rosolacci T, Ashwood T,
et al. (1999) The clomethiazole stroke
study (CLASS): Efficacy results in 545
patients classified as total anterior
circulation syndrome (TACS). J Stroke
Cerebrovasc Dis 8:231–239
Google Scholar
Muir KW, Lees KR, Ford I, Davis S;
Intravenous Magnesium Efficacy in
Stroke (IMAGES) Study Investigators
(2004) Magnesium for acute stroke
(Intravenous Magnesium Efficacy in
Stroke trial): randomised controlled
trial. Lancet 363:439–445
Article
PubMed
Google Scholar
DeGraba TJ, Hallenbeck JM, Pettigrew
KD, Dutka AJ, Kelly BJ (1999) Progression
in acute stroke.Value of the initial
NIH Stroke Scale score in patient
stratification in future trials. Stroke
30:1208–1212
PubMed
Google Scholar
The NINDS t-PA Stroke Study Group
(1997) Generalized efficacy of t-PA for
acute stroke: subgroup analysis of the
NINDS t-PA stroke trial. Stroke 28:
2119–2125
PubMed
Google Scholar
Grotta JC, Chiu D, Lu M, Patel S, Levine
SR, Tilley BC, Brott TG, et al. (1999)
Agreement and variability in the interpretation
of early CT changes in stroke
patients qualifying for intravenous
rrtPA therapy. Stroke 30:1528–1533
PubMed
Google Scholar
Warach S (2004) Early reperfusion
related to clinical response in DIAS:
phase II, randomized, placebocontrolled
dose finding trial of IV
desmoteplase 3–9 hours from onset in
patients with diffusion-perfusion
mismatch. Presented at the 29th International
Stroke Conference, San Diego,
California
Marler JR, Tilley BC, Lu M, Brott TG,
Lyden PC, Grotta JC, Broderick JP,
Levine SR, Frankel MP, Horowitz SH,
Haley EC Jr, Lewandowski CA,
Kwiatkowski TP (2000) Early stroke
treatment associated with better outcome:
the NINDS rt-PA stroke study.
Neurology 55:1649–1655
PubMed
Google Scholar
Hacke for the ATLANTIS, ECASS, and
NINDS rt-PA Study Group Investigators
(2004) Better outcome with early
stroke treatment: A pooled analysis of
ATLANTIS, ECASS, and NINDS rt-PA
stroke trials. Lancet (in press)
Kidwell CS, Liebeskind DS, Starkman
S, Saver JL (2001) Trends in acute ischemic
stroke trials through the 20th
century. Stroke 32:1349–1359
PubMed
Google Scholar
Sereghy T, Overgaard K, Boysen G
(1993) Neuroprotection by excitatory
amino acid antagonist augments the
benefit of thrombolysis in embolic
stroke in rats. Stroke 24:1702–1708
PubMed
Google Scholar
Grotta J (2001) Combination Therapy
Stroke Trial: recombinant tissue-type
plasminogen activator with/without
lubeluzole. Cerebrovasc Dis 12:258–263
Article
PubMed
Google Scholar
Liebeskind DS, Kasner SE (2001)
Neuroprotection for ischaemic stroke:
an unattainable goal? CNS Drugs
15:165–174
PubMed
Google Scholar
Krams M, Lees KR, Hacke W, Grieve
AP, Orgogozo J-M, Ford GA (2003)
Acute stroke therapy by inhibition of
neutrophils (ASTIN): An adaptive
dose-response study of UK-279.276 in
acute ischemic stroke. Stroke 34:2543–2548
Article
PubMed
Google Scholar
Dorman J, Sandercock PA (1996)
Consideration of the design of clinical
trials of neuroprotective therapy in
acute stroke. Stroke 27:1507–1515
PubMed
Google Scholar
Samsa GP, Matchar DB (2001) Have
randomized controlled trials of neuroprotective
drugs been underpowered?
An illustration of three statistical
principles. Stroke 32:669–674
PubMed
Google Scholar
Duncan PW, Jorgensen HS, Wade DT
(2000) Outcome measures in acute
stroke trials. A systematic review and
some recommendations to improve
practice. Stroke 31:1429–1438
PubMed
Google Scholar
Roberts L, Counsell C (1998) Assessment
of clinical outcomes in acute
stroke trials. Stroke 29:986–991
PubMed
Google Scholar
Young FB, Lees KR, Weir CJ for the
Glycine Antagonist in Neuroprotection
(GAIN) (2003) International Trial
Steering Committee and Investigators.
Stroke 34:2676–2680
Article
PubMed
Google Scholar
Duncan PW, Wallace D, Lai SM, Johnson
D, Embretson S, Laster LJ (1999)
The stroke impact scale version 2.0.
Evaluation of reliability, validity, and
sensitivity to change. Stroke 30:
2131–2140
PubMed
Google Scholar
Wilson JT, Hareendran A, Grant M,
Baird T, Schulz UG, Muir KW, Bone I
(2002) Improving the assessment of
outcomes in stroke: use of a structured
interview to assign grades on the
modified Rankin Scale. Stroke 33:2243–2249
Article
PubMed
Google Scholar
Weir CJ,Kaste M, Lees KR, for the
GAIN International Steering Committee
and Investigators (2003) Targeting
neuroprotective clinical trials on patients
with potential to benefit increases
statistical power and reduces
the sample size required. Presented at
the International Stroke Conference,
San Antonio, Texas
Hacke W, Kaste M, Fieschi C, von
Kummer R, Davalos A, Meier D, Larrue
V, Bluhmki E, Davis S, Donnan G,
Schneider D, Diez-Tejedor E, Trouillas
P (1998) 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 352:1245–1251
Article
PubMed
Google Scholar
Wardlaw JM, Sandercock PA, Warlow
CP, Lindley RI (2000) Trials of thrombolysis
in acute ischemic stroke: does
the choice of primary outcome measure
really matter? Stroke 31:1133–1135
PubMed
Google Scholar
Stroke Unit Trialists’ Collaboration
(2002) Organised inpatient (stroke
unit) care for stroke. Cochrane Database
Syst Rev 1:CD000197
Google Scholar
Bode-Greuel KM, Klisch J, Horvath E,
Glaser T, Traber J (1990) The effect of
BAY x 3702 on hippocampal damage
after transient forebrain ischemia in
the Mongolian gerbil. Stroke 21:164–166
Google Scholar
Horvath E, Augstein K-H, Wittka R
(1997) Neuroprotective effect of the
novel 5-HT1A receptor agonist BAY x
3702 in a rat model of permanent focal
cerebral ischemia and traumatic brain
injury (abstract). Soc Neurosci 23:1923
Google Scholar
Horvath E, Augstein K-H (1997) Neuroprotection
by the novel 5-HT1A
receptor agonist BAY x 3702 in the rat
model of acute subdural hematoma
(abstract). J Neurotrauma 14:800
Google Scholar
Teal P, on behalf of the BRAINS Study
Group (1998) BRAINS, a phase II study
of the neuroprotectant, BAY x 3702 in
patients with ischemic stroke (abstract).
Cerebrovasc Dis 8(Suppl 4):20
Article
PubMed
Google Scholar
Teal P, Lyden P,Hennerici M,Kaste M,
Davis SM, Sprenger K (2003) Design
and rationale for the modification of a
Randomized Exposure Control Trial of
repinotan in acute ischemic stroke.
Presented at the International Stroke
Conference, Phoenix, Arizona
Lees KR, Barer D, Ford GA, Hacke W,
Kostulas V, Sharma AK, et al. (2003)
Tolerability of NXY-059 at higher
target concentrations in patients with
acute stroke. Stroke 34:482–487
Article
PubMed
Google Scholar
Davis SM, Donnan GA (2002) Neuroprotection:
establishing proof of
concept in human stroke. Stroke
33:309–310
Article
PubMed
Google Scholar
Lees KR, Sharma AK, Barer D, Ford
GA,Kostulas V, Cheng Y-F, et al. (2001)
Tolerability and pharmacokinetics of
the nitrone NXY-059 in patients with
acute stroke. Stroke 32:675–680
PubMed
Google Scholar
Hacke W (2004) The DIAS Study:
results of a phase II, MRI-based dose
finding study of desmoteplase in acute
stroke. Presented at the 29th International
Stroke Conference, San Diego,
California
Google Scholar
Peterson L, Prince HC,Williams B,
Tempel D,Grotta JC (2002) ARTIST+:
AMPA Receptor Antagonist Treatment
in Ischemic Stroke Trial, YM872 +
Alteplase. Ongoing Clinical Trials
Session, 27th International Stroke
Conference
Yurko-Mauro KA, Prince HC,Williams
B, Tempel D,Warach S, for the ARTIST
MRI Study Group (2002) ARTIST MRI:
AMPA Receptor Antagonist Treatment
in Ischemic Stroke Trial-MRI. Ongoing
Clinical Trials Session, 27th International
Stroke Conference
Google Scholar
Lodder J, van Raak L, Kessels F (2001)
Early GABA-ergic activation study in
stroke. Ongoing Clinical Trials Session,
26th International Stroke Conference
van Raak L, Hilton A, Kessels F, Lodder
J (2002) Implementing the EGASIS
trial, an international multicenter
acute intervention trial in stroke.
Control Clin Trials 23:74–79
Article
PubMed
Google Scholar
IMAGES Study Investigators (2004)
Magnesium for acute stroke (Intravenous
Magnesium Efficacy in Stroke
trial): randomised controlled trial.
Lancet 363:414–415
Article
PubMed
Google Scholar
Saver JL, Kidwell CS, Hamilton S, Stratton
S, Eckstein M, Cohen S, et al. (2002)
The Field Administration of Stroke
Therapy – Magnesium (FAST-MAG)
Phase 3 Trial. Ongoing Clinical Trials
Session, 27th International Stroke Conference
Bath PMW, Willmot MR, Weaver CW,
Leonardi-Bee J, for the ENOS Investigators
(2002) Efficacy of Nitric Oxide
in Stroke (ENOS): A prospective, large,
randomised controlled trial in acute
stroke. British Association of Stroke
Physicians Conference