Clinical trial NCT00336596: Ultrasound Enhanced Thrombolytic Therapy of Middle Cerebral Artery Occlusion
Official title: Transcranial Ultrasound Enhanced Thrombolysis (TRUST)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Intracranial Embolism
Thrombosis
Keywords: middle cerebral artery occlusion
intracranial embolism and thrombosis
ultrasound enhanced thrombolysis
Patients receiving iv thrombolytic therapy (t-PA)
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
First posted: 2006-06-14
Enrollment: 400
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Symptomatic intracranial hemorrhage (safety)
measure: Functional outcome (efficacy)
Secondary outcomes:
measure: Asymptomatic intracranial hemorrhage 24-48 hours after t-PA infusion
measure: 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
measure: Mean mRS score at 90 days after t-PA infusion
measure: Death occurring during study period
measure: Recanalization at 24-48 hours after t-PA infusion
Other outcomes:
Locations:
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau, Department of Neurology
city: Basel
country: Switzerland
facility: University Hospital of Basel, Department of Neurology
city: Bern
country: Switzerland
facility: University hospital of Bern, Department of Neurology
city: Geneva
country: Switzerland
facility: University Hospital of Geneva, Department of Neurology
city: Lausanne
country: Switzerland
facility: University Hospital of Lausanne, Department of Neurology
city: Zurich
country: Switzerland
facility: University Hospital of Zurich, Department of Neurology
Study officials:
affiliation: University Hospital of Zurich, Department of Neurology, Zurich, Switzerland
name: Ralf W Baumgartner, MD
role: STUDY_CHAIR
References: