Dataset Information

THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6?mg/kg (THAWS) Trial.

ABSTRACT: Because of lack of information regarding timing of stroke, patients who suffer stroke during sleep are generally ineligible for intravenous thrombolysis, although many of these patients could potentially recover with this treatment. Magnetic resonance image findings with positive diffusion-weighted imaging and no marked parenchymal hyperintensity on fluid-attenuated inversion recovery (negative pattern) can identify acute ischemic stroke patients within 4·5?h from symptom onset.The THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6?mg/kg trial aims to determine the efficacy and safety of intravenous thrombolysis with alteplase at 0·6?mg/kg body weight, the approved dose for Japanese stroke patients, using magnetic resonance image-based selection in ischemic stroke patients with unclear time of symptom onset, and compare findings with standard treatment.This is an investigator-initiated, multicenter, prospective, randomized, open-treatment, blinded-end-point clinical trial. The design is similar to the Efficacy and Safety of MRI-based Thrombolysis in Wake-up Stroke trial. Patients with unclear-onset time of stroke symptoms beyond 4·5?h and within 12?h after the time of the last-known-well period and within 4·5?h after symptom recognition, who showed a negative fluid-attenuated inversion recovery pattern, are randomized to either intravenous thrombolysis or standard treatment.The primary efficacy end-point is modified Rankin Scale 0-1 at 90 days. The safety outcome measures are symptomatic intracranial hemorrhage at 22-36?h, and major bleeding and mortality at 90 days.This trial may help determine if low-dose alteplase at 0·6?mg/kg should be recommended as a routine clinical strategy for ischemic stroke patients with unclear-onset time.

SUBMITTER: Koga M

PROVIDER: S-EPMC4660886 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6 mg/kg (THAWS) Trial.

Koga Masatoshi M Toyoda Kazunori K Kimura Kazumi K Yamamoto Haruko H Sasaki Makoto M Hamasaki Toshimitsu T Kitazono Takanari T Aoki Junya J Seki Kenta K Homma Kazunari K Sato Shoichiro S Minematsu Kazuo K

International journal of stroke : official journal of the International Stroke Society 20140804 8

<h4>Rationale</h4>Because of lack of information regarding timing of stroke, patients who suffer stroke during sleep are generally ineligible for intravenous thrombolysis, although many of these patients could potentially recover with this treatment. Magnetic resonance image findings with positive diffusion-weighted imaging and no marked parenchymal hyperintensity on fluid-attenuated inversion recovery (negative pattern) can identify acute ischemic stroke patients within 4·5 h from symptom onset ...[more]

PMID: 25088843

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Project description:Importance:The rationale for intravenous thrombolysis in patients with lacunar infarcts is debated, since it is hypothesized that the microvascular occlusion underlying lacunar infarcts might not be susceptible to pharmacological reperfusion treatment. Objective:To study the efficacy and safety of intravenous thrombolysis among patients with lacunar infarcts. Design, Setting, and Participants:This exploratory secondary post hoc analysis of the WAKE-UP trial included patients who were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). The WAKE-UP trial was a multicenter, double-blind, placebo-controlled randomized clinical trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time, guided by magnetic resonance imaging. All 503 patients randomized in the WAKE-UP trial were reviewed for lacunar infarcts. Diagnosis of lacunar infarcts was based on magnetic resonance imaging and made by consensus of 2 independent investigators blinded to clinical information. Main Outcomes and Measures:The primary efficacy variable was favorable outcome defined by a score of 0 to 1 on the modified Rankin Scale at 90 days after stroke, adjusted for age and severity of symptoms. Results:Of the 503 patients randomized in the WAKE-UP trial, 108 patients (including 74 men [68.5%]) had imaging-defined lacunar infarcts, whereas 395 patients (including 251 men [63.5%]) had nonlacunar infarcts. Patients with lacunar infarcts were younger than patients with nonlacunar infarcts (mean age [SD], 63 [12] years vs 66 [12] years; P = .003). Of patients with lacunar infarcts, 55 (50.9%) were assigned to treatment with alteplase and 53 (49.1%) to receive placebo. Treatment with alteplase was associated with higher odds of favorable outcome, with no heterogeneity of treatment outcome between lacunar and nonlacunar stroke subtypes. In patients with lacunar strokes, a favorable outcome was observed in 31 of 53 patients (59%) in the alteplase group compared with 24 of 52 patients (46%) in the placebo group (adjusted odds ratio [aOR], 1.67 [95% CI, 0.77-3.64]). There was 1 death and 1 symptomatic intracranial hemorrhage according to Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria in the alteplase group, while no death and no symptomatic intracranial hemorrhage occurred in the placebo group. The distribution of the modified Rankin Scale scores 90 days after stroke also showed a nonsignificant shift toward better outcomes in patients with lacunar infarcts treated with alteplase, with an adjusted common odds ratio of 1.94 (95% CI, 0.95-3.93). Conclusions and Relevance:While the WAKE-UP trial was not powered to demonstrate the efficacy of treatment in subgroups of patients, the results indicate that the association of intravenous alteplase with functional outcome does not differ in patients with imaging-defined lacunar infarcts compared with those experiencing other stroke subtypes.

Project description:Background: Hemorrhagic transformation (HT) is an important complication of intravenous thrombolysis with alteplase. HT can show a wide range from petechiae to parenchymal hematoma with mass effect with varying clinical impact. We studied clinical and imaging characteristics of patients with HT and evaluated whether different types of HT are associated with functional outcome. Methods: We performed a post-hoc analysis of WAKE-UP, a multicenter, randomized, placebo-controlled trial of MRI-guided intravenous alteplase in unknown onset stroke. HT was assessed on follow-up MRI or CT and diagnosed as hemorrhagic infarction type 1 and type 2 (HI1 and HI2, combined as HI), and parenchymal hemorrhage type 1 and type 2 (PH1 and PH2, combined as PH). Severity of stroke symptoms was assessed using the National Institutes of Health Stroke Scale (NIHSS) at baseline. Stroke lesion volume was measured on baseline diffusion weighted imaging (DWI). Primary endpoint was a favorable outcome defined as a modified Rankin Scale score 0-1 at 90 days. Results: Of 483 patients included in the analysis, 95 (19.7%) showed HI and 21 (4.4%) had PH. Multiple logistic regression analysis identified treatment with alteplase (OR, 2.08 [95% CI, 1.28-3.40]), baseline NIHSS score (OR, 1.11 [95% CI, 1.05-1.17]), DWI lesion volume (OR, 1.03 [95% CI, 1.01-1.05]), baseline glucose levels (OR, 1.01 [95% CI, 1.00-1.01]) and atrial fibrillation (OR, 3.02 [95% CI, 1.57-5.80]) as predictors of any HT. The same parameters predicted HI. Predictors of PH were baseline NIHSS score (OR, 1.11 [95% CI, 1.01-1.22]) and as a trend treatment with alteplase (OR, 2.40 [95% CI, 0.93-6.96]). PH was associated with lower odds of favorable outcome (OR 0.25, 95% [CI 0.05-0.86]), while HI was not. Conclusion: Our results indicate that HI is associated with stroke severity, cardiovascular risk factors and thrombolysis. PH is a rare complication, more frequent in severe stroke and with thrombolysis. In contrast to HI, PH is associated with worse functional outcome. The impact of HT after MRI-guided intravenous alteplase for unknown onset stroke on clinical outcome is similar as in the trials of stroke thrombolysis within a known early time-window.

Dataset Information

THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6?mg/kg (THAWS) Trial.

Publications

THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6 mg/kg (THAWS) Trial.

Similar Datasets

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