Interventional Management of Stroke (IMS) II Study

Phase 2

Completed

Conditions: Stroke

Registration Number: NCT00243906

Lead Sponsor: University of Cincinnati

Brief Summary: The purpose of this study is to examine the effects of delivering intra-arterial recombinant tissue plasminogen activator (rt-PA) and ultrasound to the site of the blood clot blocking blood flow to the brain of stroke patients.

Detailed Description: The overall goal of Interventional Management of Stroke (IMS II) study is to refine thrombolytic therapy for patients with acute ischemic stroke who can be treated within three hours of stroke onset.

This multi-center, non-randomized pilot study will provide preliminary data about the benefits and risks of combined intravenous (IV) and intra-arterial (IA) recombinant tissue plasminogen activator (rtPA) and low-intensity ultrasound energy in ischemic stroke patients with baseline NIHSSS \>/= 10 in whom intravenous treatment can be started within three hours of stroke onset. rt-PA is a thrombolytic, clot-dissolving drug.

The primary objectives for the study are to obtain reliable estimates of the effectiveness and safety of a treatment approach combining IV/IA rt-PA and ultrasound for stroke patients; and to determine if the estimated effectiveness of combined IV/IA rt-PA at 3 months-as compared to the 3 month outcome of placebo-treated patients in the NINDS rt-PA Stroke Trial-warrants proceeding to a large, phase III randomized trial.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 81

Inclusion Criteria

Age: 18 through 80 years (i.e., candidates must have had their 18th birthday, but not had their 81st birthday)
Initiation of intravenous rt-PA within 3 hours of onset of stroke symptoms. Time of onset is defined as the last time when the subject was witnessed to be at baseline (i.e., subjects who have stroke symptoms upon awakening will be considered to have their onset at beginning of sleep)
An NIHSSS >/= 10 at the time that intravenous rt-PA is begun

Exclusion Criteria

History of stroke in the past 3 months
Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arteriovenous malformation
Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT scan is normal
Hypertension at time of treatment; systolic BP > 185 or diastolic > 110 mm Hg) or aggressive measures to lower blood pressure to below these limits are needed.
Presumed septic embolus
Presumed pericarditis, including pericarditis after acute myocardial infarction
Recent (within 30 days) surgery or biopsy of parenchymal organ
Recent (within 30 days) trauma, with internal injuries or ulcerative wounds
Recent (within 90 days) severe head trauma or head trauma with loss of consciousness
Any active or recent (within 30 days) hemorrhage
Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency or oral anticoagulant therapy with INR > 1.5 or institutionally equivalent prothrombin time
Females of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission
Baseline lab values: glucose < 50mg/dl or > 400mg/dl, platelets <100,000, or Hct <25
Subjects that require hemodialysis or peritoneal dialysis
Subjects who have received heparin within 48 hours must have a normal partial thromboplastin time (PTT) to be eligible
Subjects with an arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days
Subjects with a seizure at onset of stroke
Subjects with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations
Other serious, advanced, or terminal illness
Any other condition that the investigator feels would pose a significant hazard to the subject if Activase (Alteplase) therapy is initiated
Current participation in another research drug treatment protocol; subject cannot start another experimental agent until after 90 days
Informed consent is not or cannot be obtained. For example, obtunded subjects are not automatically excluded from the study. However, if the next of kin or legal guardian (i.e., the individual legally empowered in the state where the consent is obtained) cannot provide consent, randomization and entry into the study could not proceed

CT Scan Exclusion Criteria:

High density lesion consistent with hemorrhage of any degree
Significant mass effect with midline shift
Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT scan. Sulcal effacement and/or loss of grey-white differentiation alone are not contraindications for treatment

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Primary Safety Endpoint	36 hours after completion of rt-PA infusion	Development of intracerebral hematoma or hemorrhagic infarction with clinical deterioration likely to result in permanent disability or death, or other severe systemic bleeding complications such as groin hematoma, retroperitoneal hematoma, or gastrointestinal bleeding requiring transfusion of 3 units of blood replacement or major surgical intervention.
Primary Angiographic Outcome	60 minutes after start of IA therapy	The primary revascularization end point was complete (arterial occlusive lesion III) recanalization of the targeted arterial occlusion at 60 minutes after the start of IA rt-PA and ultrasound therapy,
Primary Outcome Measure	3 months following treatment	modified Rankin Score of 0 or 1