Microbubbles and Ultrasound in Stroke Trial: MUST Study

Terminated

Phase 2 Results N/A

Trial Description

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

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

Interventions

  • Ultrasound Device
    Intervention Desc: 2-MHz, low intensity transcranial ultrasound
    ARM 1: Kind: Experimental
    Label: 1
    Description: Levovist
  • Levovist (D-Galactose palmityl coated microbubbles) Drug
  • Levovist Drug
    Other Names: Levovist
    Intervention Desc: D-Galactose and palmitic palmitique intravenous 4 g
    ARM 1: Kind: Experimental
    Label: 1
    Description: Levovist

Trial Design

  • Allocation: Randomized
  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

Patients will receive transcranial, 2-MHz, low-intensity ultrasound focused on middle cerebral artery stem combined with intravenous galactose-based microbubbles (Levovist).

Outcomes

Type Measure Time Frame Safety Issue
Primary Recanalization rate on CT or MR angiography at 4 to 8 hours after symptom onset.
Secondary Recanalization rate on TCD at 24 hours. Proportion of patients with clinical improvement at end of treatment and 24 hours measured by NIHSS. Proportion of hemorrhagic transformations at 24-36 hours. Proportion of patients scoring 0, 1, or 2 on the modified Rankin scale at 3 months.
Primary Rate of early recanalization on post-treatment MR or CT angiography. Recanalization is described using the tIMI classification. Yes
Secondary Rate of symptomatic intracerebral hemorrhage, mortality, Score on the modified Rankin scale 3 months Yes

Sponsors