Ultrasound Enhanced Thrombolytic Therapy of Middle Cerebral Artery Occlusion

Recruiting

Phase 3 Results N/A

Trial Description

The purpose of the present, randomized, controlled multicenter phase III trial is to investigate the safety and efficacy of continuous 1-hour insonation of occluded middle cerebral artery with 2 MHz TCCS in stroke patients treated with intravenous tissue plasminogen activator (t-PA) within 3 hours after symptom onset.

Detailed Description

Thrombolysis with intravenous(iv) tissue plasminogen activator (t-PA) is the only effective and approved therapy for acute ischemic stroke. The most frequent cause of ischemic stroke is thrombosis of the middle cerebral artery (MCA). Preliminary in vitro, animal and human studies suggest that ultrasound accelerates thrombolysis induced by t-PA, and recanalization of acute MCA occlusion due to thrombolysis is an independent predictor of good clinical outcome. Thus, insonation of an occluded MCA through the temporal bone in stroke patients who are treated with iv t-PA might enhance recanalization and improve clinical outcome. The present prospective, randomized, controlled multicenter pilot study will investigate the safety and efficacy of continuous 1-hour insonation of the occluded MCA with 2 MHz transcranial color duplex sonography in patients with ischemic stroke treated with iv t-PA within 3 hours after symptom onset. It is planned to randomize 400 patients in 6 Swiss centers during an enrolment period of 33 months with an individual follow up of 3 months. The study endpoints include safety and efficacy assessments. The primary safety endpoint is to determine the rate of symptomatic intracranial hemorrhage (ICH) in both treatment groups. The primary efficacy endpoint is to determine whether a good functional outcome (modified Rankin scale, mRs, score of 0-2) differs between both treatment groups. Secondary endpoints include (1) asymptomatic ICH occuring during or within the first 24-48 hours after t-PA infusion, (2) early clinical recovery by 10 or more National Institute of Health Stroke Scale (NIHSS) points or dramatic recovery (total NIHSS score of 3 or less) at 24-48 hours after t-PA infusion, (3) mean mRS score at 90 days after t-PA infusion, (4) death occuring during the study period, and (5) recanalization at 24-48 hours after t-PA infusion.

Conditions

Interventions

Trial Design

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

Patient Involvement

All patients will be randomized to one of two groups, with the treatment group receiving continuous 1-hour insonation of the occluded MCA with 2 MHz transcranial color duplex sonography (TCCS) in addition to the iv t-PA given within 3 hours after symptom onset to the control group.

Outcomes

Type Measure Time Frame Safety Issue
Primary Efficacy endpoint: functional outcome (modified Rankin scale) Safety endpoint: rate of symptomatic intracranial hemorrhage (ICH)
Secondary Asymptomatic ICH occurring during or within the first 24-48 hours after t-PA infusion; early clinical recovery by >9 National Institute of Health Stroke Scale (NIHSS) points or dramatic recovery (total NIHSS score <4) at 24-48 hours after t-PA infusion; mean mRS score at 90 days after t-PA infusion; mortality rate during the study period; and recanalization at 24-48 hours after t-PA infusion.
Primary Symptomatic intracranial hemorrhage (safety)
Primary Functional outcome (efficacy)
Secondary Asymptomatic intracranial hemorrhage 24-48 hours after t-PA infusion
Secondary Early clinical recovery by 10 or more NIHSS points or dramatic recovery (total NIHSS 3 or less)at 24-48 hours after t-PA infusion
Secondary Mean mRS score at 90 days after t-PA infusion
Secondary Death occurring during study period
Secondary Recanalization at 24-48 hours after t-PA infusion

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