Ultrasound Enhanced Thrombolytic Therapy of Middle Cerebral Artery Occlusion

Transcranial Ultrasound Enhanced Thrombolysis (TRUST)

Sponsors

Lead Sponsor: University of Zurich

Collaborator: Swiss National Science Foundation

Source University of Zurich
Brief Summary

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.

Overall Status Unknown status
Start Date 2006-06-01
Completion Date 2009-06-01
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Symptomatic intracranial hemorrhage (safety)
Functional outcome (efficacy)
Secondary Outcome
Measure Time Frame
Asymptomatic intracranial hemorrhage 24-48 hours after t-PA infusion
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
Mean mRS score at 90 days after t-PA infusion
Death occurring during study period
Recanalization at 24-48 hours after t-PA infusion
Enrollment 400
Condition
Intervention

Intervention Type: Procedure

Intervention Name: transcranial ultrasound in patients treated with iv t-PA

Eligibility

Criteria:

Inclusion Criteria: - acute ischemic stroke in the MCA territory according to clinical and cranial computed tomography (CT) or cranial MR imaging (MRI) findings - patient undergoing iv thrombolysis with t-PA within 3 hours after stroke onset - Occlusion of sphenoidal (M1) or insular (M2) segment of the MCA at CT (CTA), MR (MRA) or catheter (CA) angiography - appropriate temporal bony window without echocontrast agents for insonation with TCCS - full functional independence prior to present stroke (mRS 0-1), use of a cane for walking due to comorbid condition is acceptable - written informed consent, signed and dated by the subject (or subject's authorized representative, if allowed by local laws) and by the person obtaining the consent, indicating agreement to comply with all protocol-specific procedures Exclusion Criteria: - unconsciousness (more than 2 points on item 1a on NIHSS) - history of intracranial hemorrhage, arteriovenous malformation or aneurysm - severe cranio-cerebral trauma within the last 3 months - symptoms of subarachnoidal hemorrhage - time of symptom onset unclear - large surgical intervention or trauma within the last 10 days - expected survival below 90 days after iv t-PA treatment - severe hepatic disease, esophageal varices, acute pancreatitis - septic embolism, endocarditis, pericarditis after myocardial infarction - pregnancy or childbirth within the last 30 days or nursing mothers - history of hemorrhagic diathesis or coagulopathy - untreatable increase of arterial blood pressure (>185mmHg systolic, >110mmHg diastolic) - intracranial hemorrhage, arteriovenous malformations or aneurysm at brain imaging - thrombocytes <100'000 per microliter - international normalized ratio (INR)>1.7 or partial thromboplastin time (PTT) prolongated - serum glucose <2.7mmol/l or >22.2mmol/l - severe renal insufficiency or other contraindications against CT-contrast agents

Gender:

All

Minimum Age:

N/A

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Ralf W Baumgartner, MD Study Chair University Hospital of Zurich, Department of Neurology, Zurich, Switzerland
Overall Contact

Last Name: Ralf W Baumgartner, MD

Phone: +41 1 255 56 86

Email: [email protected]

Location
Facility: Status: Contact: Investigator:
Kantonsspital Aarau, Department of Neurology | Aarau, Switzerland Recruiting Hansjörg Hungerbühler, MD +41 62 838 66 75 [email protected] Hansjörg Hungerbühler, MD Principal Investigator
University Hospital of Basel, Department of Neurology | Basel, Switzerland Recruiting Stefan Engelter, MD +41 61 265 25 25 [email protected] Philippe Lyrer, MD Principal Investigator Stefan Engelter, MD Principal Investigator
University hospital of Bern, Department of Neurology | Bern, Switzerland Recruiting Marcel Arnold, MD +41 31 632 33 32 [email protected] H.-P. Mattle, MD Principal Investigator Marcel Arnold, MD Principal Investigator
University Hospital of Geneva, Department of Neurology | Geneva, Switzerland Recruiting Roman Sztajzel, MD +41 22 372 83 10 [email protected] Roman Sztajzel, MD Principal Investigator
University Hospital of Lausanne, Department of Neurology | Lausanne, Switzerland Recruiting Patrik Michel, MD +41 21 314 11 85 [email protected] Patrik Michel, MD Principal Investigator
University Hospital of Zurich, Department of Neurology | Zurich, 8091, Switzerland Recruiting Ralf W Baumgartner, MD +41 1 255 56 86 [email protected] Ralf W Baumgartner, MD Principal Investigator Dimitrios Georgiadis, MD Principal Investigator Hakan Sarikaya, MD Sub-Investigator
Location Countries

Switzerland

Verification Date

2007-04-01

Keywords
Has Expanded Access No
Condition Browse
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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