Microbubbles and Ultrasound in Stroke Trial: MUST Study

Study Overview
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Brief Summary
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To determine whether transcranial 2-MHz ultrasound combined with intravenous administration of microbubbles improves early recanalization in patients with acute ischemic stroke caused by middle cerebral artery (MCA) proximal occlusion treated with intravenous alteplase within 3 hours of symptom onset.

Detailed Description
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Proximal MCA occlusion is recognized using MR or CT angiography performed before inclusion. All patients are treated with alteplase according to current guidelines. In addition, patients randomized in the active group are continuously exposed to transcranial 2-MHz ultrasound for 1 hour combined with intravenous administration of microbubbles. Controls are only treated with alteplase. The ultrasound beam is positioned at the thrombus/blood flow interface using color-coded sonography. Galactose-based microbubbles are administered via continuous intravenous infusion over 40 min. Early recanalization is assessed using MR or CT angiography 4 to 8 hours after symptom onset. The evaluation of angiograms is performed by 2 neuroradiologists blinded to group of randomization and clinical details. The primary outcome measure is the rate of early recanalization. Recanalization is assessed using the TIMI classification. Secondary endpoints include the rate of symptomatic intracerebral hemorrhage, mortality, and functional outcome on the modified Rankin scale at 3 months.

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Radiation: Ultrasound
* Drug: Levovist


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute ischemic stroke MCA proximal occlusion on CT or MR angiography Thrombolysis with intravenous alteplase initiated within 3 hours of stroke onset

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Levovist | Radiation: Ultrasound<br>* 2-MHz, low intensity transcranial ultrasound<br>Drug: Levovist<br>* D-Galactose and palmitic palmitique intravenous 4 g<br>|
| No Intervention: 2<br>No specific intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of early recanalization on post-treatment MR or CT angiography. Recanalization is described using the tIMI classification. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of symptomatic intracerebral hemorrhage, mortality, Score on the modified Rankin scale |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, thrombolysis, ultrasound, microbubbles, alteplase