Granulocyte colony-stimulating factor for acute ischemic stroke: a randomized controlled trial. 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. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. A pilot study with monosialoganglioside GM1 on acute cerebral ischemia. Abciximab in acute ischemic stroke. A randomized, double-blind, placebo-controlled, dose-escalation study.
Because granulocyte colony-stimulating factor (G-CSF) has anti-inflammatory and neuroprotective properties and is known to mobilize stem cells, it may be useful in the treatment of acute ischemic stroke. We sought to examine the feasibility, safety and efficacy of using G-CSF to treat acute stroke.
                We conducted a randomized, blinded controlled trial involving 10 patients with acute cerebral infarction (middle cerebral artery territory as documented by the admission MRI) who presented within 7 days of onset and whose scores on the National Institutes of Health Stroke Scale (NIHSS) were between 9 and 20. Patients were assigned to either G-CSF therapy or usual care. The G-CSF group (n = 7) received subcutaneous G-CSF injections (15 microg/kg per day) for 5 days. The primary outcome was percentage changes between baseline and 12-month follow-up in mean group scores on 4 clinical scales: the NIHSS, European Stroke Scale (ESS), ESS Motor Subscale (EMS) and Barthel Index (BI). We also assessed neurologic functioning using PET to measure cerebral uptake of fluorodeoxyglucose in the cortical areas surrounding the ischemic core.
                All of the patients completed the 5-day course of treatment, and none were lost to follow-up. No severe adverse effects were seen in patients receiving G-CSF. There was greater improvement in neurologic functioning between baseline and 12-month follow-up in the G-CSF group than in the control group (NIHSS: 59% change in the mean G-CSF group score v. 36% in the mean control group score, ESS: 33% v. 20%, EMS: 106% v. 58%, BI: 120% v. 60%). Although at 12 months there was no difference between the 2 groups in cerebral uptake of fluorodeoxyglucose in the ischemic core, uptake in the area surrounding the core was significantly improved in the G-CSF group compared with the control group. There was positive correlation between metabolic activity and EMS score following simple linear correlation analysis.
                Our preliminary evidence suggests that using G-CSF as therapy for acute stroke is safe and feasible and leads to improved neurologic outcomes. Recombinant tissue-type plasminogen activator (rt-PA) improves outcomes for patients with acute ischemic stroke, but current approved use is limited to within 3 hours of symptom onset. This restricts the number of patients who can be treated, since most stroke patients present more than 3 hours after symptom onset.
                To test the efficacy and safety of rt-PA in patients with acute ischemic stroke when administered between 3 and 5 hours after symptom onset.
                The Alteplase ThromboLysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study is a phase 3, placebo-controlled, double-blind randomized study conducted between December 1993 and July 1998, with up to 90 days of follow-up.
                One hundred forty university and community hospitals in North America.
                An intent-to-treat population of 613 acute ischemic stroke patients was enrolled, with 547 of these treated as assigned within 3 to 5 hours of symptom onset. A total of 39 others were treated within 3 hours of symptom onset, 24 were treated more than 5 hours after symptom onset, and 3 never received any study drug.
                Administration of 0.9 mg/kg of rt-PA (n = 272) or placebo (n = 275) intravenously over 1 hour.
                Primary efficacy was an excellent neurologic recovery at day 90 (National Institutes of Health Stroke Scale [NIHSS] score of < or =1); secondary end points included excellent recovery on functional outcome measures (Barthel index, modified Rankin scale, and Glasgow Outcome Scale) at days 30 and 90. Serious adverse events were also assessed.
                In the target population, 32% of the placebo and 34% of rt-PA patients had an excellent recovery at 90 days (P = .65). There were no differences on any of the secondary functional outcome measures. In the first 10 days treatment with rt-PA significantly increased the rate of symptomatic intracerebral hemorrhage (ICH) (1.1% vs 7.0% [P<.001]), a symptomatic ICH (4.7% vs 11.4% [P = .004]), and fatal ICH (0.3% vs 3.0% [P<.001]). Mortality at 90 days was 6.9% with placebo and 11.0% with rt-PA (P = .09). Results in the intent-to-treat population were similar.
                This study found no significant rt-PA benefit on the 90-day efficacy end points in patients treated between 3 and 5 hours. The risk of symptomatic ICH increased with rt-PA treatment. These results do not support the use of intravenous rt-PA for stroke treatment beyond 3 hours. Septic shock may be associated with relative adrenal insufficiency. Thus, a replacement therapy of low doses of corticosteroids has been proposed to treat septic shock.
                To assess whether low doses of corticosteroids improve 28-day survival in patients with septic shock and relative adrenal insufficiency.
                Placebo-controlled, randomized, double-blind, parallel-group trial performed in 19 intensive care units in France from October 9, 1995, to February 23, 1999.
                Three hundred adult patients who fulfilled usual criteria for septic shock were enrolled after undergoing a short corticotropin test.
                Patients were randomly assigned to receive either hydrocortisone (50-mg intravenous bolus every 6 hours) and fludrocortisone (50- micro g tablet once daily) (n = 151) or matching placebos (n = 149) for 7 days.
                Twenty-eight-day survival distribution in patients with relative adrenal insufficiency (nonresponders to the corticotropin test).
                One patient from the corticosteroid group was excluded from analyses because of consent withdrawal. There were 229 nonresponders to the corticotropin test (placebo, 115; corticosteroids, 114) and 70 responders to the corticotropin test (placebo, 34; corticosteroids, 36). In nonresponders, there were 73 deaths (63%) in the placebo group and 60 deaths (53%) in the corticosteroid group (hazard ratio, 0.67; 95% confidence interval, 0.47-0.95; P =.02). Vasopressor therapy was withdrawn within 28 days in 46 patients (40%) in the placebo group and in 65 patients (57%) in the corticosteroid group (hazard ratio, 1.91; 95% confidence interval, 1.29-2.84; P =.001). There was no significant difference between groups in responders. Adverse events rates were similar in the 2 groups.
                In our trial, a 7-day treatment with low doses of hydrocortisone and fludrocortisone significantly reduced the risk of death in patients with septic shock and relative adrenal insufficiency without increasing adverse events. Reported here are the results of an open controlled study on the use of GM1 in cases of ischemic strokes in its acute phase. A statistically significant improvement was observed in cases treated with GM1 for neurological deficits (assessed by Mathew's rating scale, modified by Fritz-Werner) at 21, 60 and 120 days and for disability at 120 days. Abciximab is a potent parenterally administered platelet glycoprotein IIb/IIIa antagonist. Because this agent has been shown to improve outcomes in coronary artery disease, there is interest to evaluate whether it could improve cerebral perfusion and outcomes after ischemic stroke. This study was designed to evaluate the safety of abciximab in acute ischemic stroke and to obtain pilot efficacy data.
                We conducted a randomized, double-blind, placebo-controlled, dose-escalation trial. Seventy-four eligible and consenting patients presenting within 24 hours after ischemic stroke onset at 38 study sites were randomly allocated to receive either an escalating dose of abciximab (54 patients) or placebo (20 patients) in a ratio of 3:1. We studied 4 escalating doses of abciximab. Patients underwent a scheduled follow-up head CT scan 24 to 36 hours after the completion of study agent administration to monitor for bleeding complications and were evaluated through 3 months.
                There were no cases of major intracranial hemorrhage. Asymptomatic parenchymal hemorrhages were detected on post-study agent CT in 4 of 54 abciximab patients (7%) and in 1 of 20 placebo patients (5%). Six additional abciximab patients had asymptomatic hemorrhagic lesions detected by unscheduled brain imaging during their follow-up period. Nine of 11 patients with asymptomatic hemorrhage had a baseline National Institutes of Health Stroke Scale score >14. At 3 months, there was a trend toward a higher rate of minimal residual disability (Barthel Index > or =95 or modified Rankin scale < or =1) among abciximab patients compared with those who received placebo.
                Abciximab appears to be safe when administered up to 24 hours after stroke onset, and it might improve functional outcome.
There is not enough evidence to evaluate corticosteroid treatment for people with acute presumed ischaemic stroke. The conclusions are unchanged since the previous update.