Clinical trial NCT00243906: Interventional Management of Stroke (IMS) II Study
Official title: Interventional Management of Stroke (IMS) II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stroke
Keywords: acute ischemic stroke
stroke
rt-PA
thrombolytic
recombinant tissue plasminogen activator
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2005-10-25
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Primary Safety Endpoint
timeFrame: 36 hours after completion of rt-PA infusion
measure: Primary Angiographic Outcome
timeFrame: 60 minutes after start of IA therapy
measure: Primary Outcome Measure
timeFrame: 3 months following treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Joseph P. Broderick, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cincinnati
name: Thomas A. Tomsick, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: IMS II Trial Investigators. The Interventional Management of Stroke (IMS) II Study. Stroke. 2007 Jul;38(7):2127-35. doi: 10.1161/STROKEAHA.107.483131. Epub 2007 May 24.