Interventional Management of Stroke (IMS) Study

Condition(s) targeted: Stroke

Intervention: recombinant tissue plasminogen activator (Drug); low-intensity ultrasound (Procedure)

Phase: Phase 2

Status: Completed

Sponsored by: National Institute of Neurological Disorders and Stroke (NINDS)

Official(s) and/or principal investigator(s):
Joseph P. Broderick, MD, Principal Investigator, Affiliation: University of Cincinnati
Thomas A. Tomsick, MD, Principal Investigator, Affiliation: University of Cincinnati

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

Official title: Interventional Management of Stroke (IMS) Study

Study design: Treatment, Non-Randomized, Open Label

Primary outcome:

Efficacy endpoint is a modified Rankin Score of 0 or 1 at 3 months

the primary angiographic outcome measure will be the rate of TIMI Grade 3 recanalization of the targeted occluded vessel at one hour after start of IA rt-PA plus ultrasound therapy.

Detailed description: The overall goal of Interventional Management of Stroke (IMS) 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.

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

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

University of Cincinnati, Cincinnati, Ohio 45267, United States

Related publications:

The IMS II Trial Investigators. The Interventional Management of Stroke (IMS) II Study. Stroke. 2007 Jul;38(7):2127-35. Epub 2007 May 24.

Starting date: January 2003
Last updated: June 27, 2007