Stroke trials

Hacke W, Albers G, Al-Rawi Y, Bogousslavsky J, Davalos A, Eliasziw M, Fischer M, Furlan A, Kaste M, Lees KR, Soehngen M, Warach S, Group DS. 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. 

Clark WM, Albers GW, Madden KR Hamilton S. The rtPA (alteplase) 0- to 6-hour acute stroke trial, part a (a0276g) results of a double-bhnd, placebo-controlled, multicenter study. Thrombolytic Therapy in Acute Ischemic Stroke Study Investigators. Stroke. 2000 31 811-816. 

Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JR, Brott T, Frankel M, Grotta JC, Haley EC, Jr., Kwiatkowski T, Levine SR, Lewandowski C, Lu M, Lyden R, Marler JR, Patel S, Tilley BC, Albers G, Bluhmki E, Wilhelm M, Hamilton S. Association of outcome with early stroke treatment Pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004 363 768-774. 

Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Multicentre Acute Stroke Trial-Italy (MAST-I)... 

Thrombolytic therapy with streptokinase in acute ischemic stroke. The Multicenter Acute Stroke Trial-Europe study group. N Engl J Med. 1996 335 145-150. 

Generalized efficacy of t-pa for acute stroke. Subgroup analysis of the NINDS t-pa stroke trial. Stroke. 1997 28 2119-2125. 

OR 1.81, 95% Cl 1.46-2.24), most of which were related to symptomatic intracranial hemorrhage (OR 3.37, 95% Cl 2.68. 22). In addition, a pooled analysis of six major randomized placebo-controlled IV rt-PA stroke trials (Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) I and II, European Cooperative Acute Stroke Study (ECASS) I and II, and NINDS I and II), including 2775 patients who were treated with IV rt-PA or placebo within 360 minutes of stroke onset, confirmed the beneht up to 3 hours and suggested a potential beneht beyond 3 hours for some patients. The pattern of a decreasing chance of a favorable 3-month outcome as the time interval from stroke onset to start of treatment increased was consistent with the findings of the original NINDS study. ... 

The Interventional Management of Stroke (IMS I) Study was a multicenter, open-labeled, single-arm pilot study in which 80 patients (median NIHSS 18) were enrolled to receive IV rt-PA (0.6 mg/kg, 60 mg maximum, 15% of the dose as a bolus with the remainder administered over 30 minutes) within 3 hours of stroke onset (median time to initiation 140 minutes). " Additional rt-PA was subsequently administered via a microcatheter at the site of the thrombus in 62 of the 80 patients, up to a total dose of 22 mg over 2 hours of infusion or until complete recanalization. Primary comparisons were with similar subsets of the placebo and rt-PA-treated subjects from the NINDS rt-PA Stroke Trial. The 3-month mortality in IMS I subjects (16%) was numerically lower but not statistically different than the mortality of the placebo (24%) or rt-PA-treated subjects (21%) in the NINDS rt-PA Stroke Trial. The rate of symptomatic ICH (6.3%) in IMS I subjects was similar to that of the rt-PA-treated subjects (6.6%) but higher than the rate in the... 

Haley Jr EC, Lewandowski C, Tilley BC. Myths regarding the NINDS rt-PA Stroke Trial setting the record straight. Ann Emerg Med 1997 30 676-682. 

Kidwell CS, Liebeskind DS, Starkman S, Saver JL. Trends in acute ischemic stroke trials through the 20th century. Stroke 2001 32 1349-1359. 

Enlimomab Acute Stroke Trial Investigators. Use of anti-icam-1 therapy in ischemic stroke results of the enlimomab acute stroke trial. Neurology 2001 57 1428-1434. 

Eisher M, Hanley DE, Howard G, Jauch EC, Warach S. Recommendations from the stair V meeting on acute stroke trials, technology and outcomes. Stroke 2007 38 245-248. 

Lodder J, van Raak L, Hilton A, Hardy E, Kessels A. Diazepam to improve acute stroke outcome results of the early gaba-ergic activation study in stroke trial. A randomized double-blind placebo-controlled trial. Cerebrovasc Dis 2006 21 120-127. 

Muir KW, Lees KR, Ford I, Davis S. Magnesium for acute stroke (intravenous magnesium efficacy in stroke trial) randomised controlled trial. Lancet 2004 363 439 45. 

Grotta J. Combination therapy stroke trial recombinant tissue-t3fpe plasminogen activator with/without lubeluzole. Cerebrovasc Dis 2001 12 258-263. 

Rusyniak DE, Kirk MA, May JD, Kao LW, Brizendine EJ, Welch JL, Cordell WH, Alonso RJ. Hyperbaric oxygen therapy in acute ischemic stroke results of the hyperbaric oxygen in acute ischemic stroke trial pilot study. Stroke 2003 34 571-574. 

Scott JF, Robinson GM, French JM, O Connell JE, Alberti KG, Gray CS. Glucose potassium insulin infusions in the treatment of acute stroke patients with mild to moderate hyperglycemia the glucose insulin in stroke trial (GIST). Stroke 1999 30 793-799. 

Placebo-Controlled Trials ofUFH, LMWH, and Heparinoids The International Stroke Trial (1ST) was a randomized, placebo-controlled trial of UFH (5000 or 12,500 lU twice daily) and aspirin (300 mg) in 19,435 unselected patients with acute stroke within 48 hours of symptom onset. Because of limited availability of neuroimaging, 33% of participants were enrolled with suspected but not proven ischemic stroke, some of whom may have suffered primary intracerebral hemorrhage (ICH). 

The Heparin in Acute Embolic Stroke Trial (HAEST) was a multicenter, randomized trial of the effect of LMWH (dalteparin 100 lU/kg sc twice daily) or aspirin (160 mg once daily) for the acute treatment of 449 patients with ischemic stroke and atrial fibrillation (AF). The primary outcome was the rate of recurrent stroke within 14 days. No difference in rates of early recurrence (8.5% dalteparin treated vs. 7.5% aspirin treated) or good 3-month functional outcome was found. The frequency of early slCH was 2.7% on dalteparin versus 1.8% on aspirin. 

In the Multicenter Acute Stroke Trial Italy (MAST-I) study, 622 patients were randomized in a 2 X 2 factorial design to receive either a 1-hour infusion of 1.5 lU streptokinase or 300 mg aspirin or both, or neither. Streptokinase (alone or with aspirin) was associated with a greater number of fatahties at 10 days (OR 2.7,95% Cl 1.7. 3). In MAST-I, neither aspirin monotherapy nor combination therapy reduced the primary outcome of combined 6-month fatahty and severe disability. 

The abciximab in Acute Ischemic Stroke trial was a randomized, placebo-controlled dose-escalation study to examine the safety of abciximab in acute stroke. It randomized 74 patients within 24 hours of stroke onset to receive one of four doses of abciximab (by bolus with or without additional infusion, 54 patients) or placebo (20 patients). The median baseline National Institute of Health Stroke Scale (NIHSS) score was 15. The rates of asymptomatic ICH were 19% in the intervention group compared to 5% in the placebo group p = 0.07). Most (9 of 11) of the asymptomatic ICH patients had more severe stroke (NIHSS >14). No cases of symptomatic ICH or major systemic bleeding occurred. There was a trend toward a lower rate of stroke recurrence (2% vs. 5%) and a higher rate of functional recovery at 3 months in the group treated with abciximab than with placebo. 

International Stroke Trial Collabarative Group. The International Stroke Trial (1ST) a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischemic stroke. Lancet 1997 349 1569-1581. 

CAST (Chinese Acute Stroke Trial) Collaborative Group. CAST randomised placebo-controUed trial of early aspirin use in 20,000 patients with acute ischemic stroke. Lancet 1997 349(9066) 1641-1649. 

Stroke Trials Registry. Abciximab in Emergent Stroke Treatment Trial - 11. www. strokecenter.org/trials. Accessed on July 15, 2007. 

Erankel MR, Morgenstem LB, Kwiatkowski T, Lu M, Tilley BC, Broderick JP, Libman R, Levine SR, Brott T. Predicting poor prognosis after acute ischemic stroke an analysis of the placebo group from the NINDS rt-PA stroke trial. Neurology 2000 54 A89. 

Alteplase (rt-PA Activase) is an IV thrombolytic (fibrinolytic) that was approved for acute stroke treatment in 1996 based on the results of the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial.10 The current American Stroke Association guidelines include alteplase as the only Food and Drug Administration (FDA) approved acute treatment for ischemic stroke and strongly encourage early diagnosis and treatment of appropriate patients.11... 

Aspirin in acute ischemic stroke has been studied in two large, randomized trials, the International Stroke Trial and the Chinese Acute Stroke Trial.20,21 Patients who received aspirin within 24 to... 

The ATLANTIS, ECASS and NINDS rt-PA Study Group Investigators. Association of outcome with early stroke treatment pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 2004 363 768-74. 

The Desmoteplase in Acute Ischemic Stroke Trial (DIAS) was based on MRI and included patients... 

A Potential Thrombolysis Algorithm 34 3A.2.3 Improving Acute Stroke Trial Design Using MRI 35... 

The positive National Institute of Neurological Disorders and Stroke trial of tissue plasminogen activator (tPA) for stroke in 1995 heralded the start of the thrombolytic era for stroke (National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group 1995). This trial showed that tPA, if given within 3 h of stroke onset, increased independent survival by 30%, with a 12% absolute increase in the number of patients with no, or minimal disability. Other large trials testing thrombolysis within 6 h of stroke onset have been less positive (Hacke etal. 1995,1998). As a consequence thrombolysis is not a universally accepted routine treatment for stroke and remains the subject of intense debate and research. Despite this, stroke thrombolysis has the potential to dramatically improve the outcome of many patients with severe... 

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