Methodology of the Interventional Management of Stroke III Trial.
BACKGROUND
The Interventional Management of Stroke (IMS) I and II pilot trials demonstrated that the combined intravenous (i.v.) and intraarterial (i.a.) approach to recanalization may be more effective than standard i.v. rt-PA (Activase) alone for moderate-to-large National Institutes of Health Stroke Scale (NIHSS>or=10) strokes, and with a similar safety profile.


OBJECTIVE
The primary objective of this NIH-funded, Phase III, randomized, multicenter, open-label clinical trial is to determine whether a combined i.v./i.a. approach to recanalization is superior to standard i.v. rt-PA alone when initiated within 3 h of acute ischemic stroke onset. The IMS III trial will develop and maintain a network of interventional centers to test the safety, feasibility, and potential efficacy of new FDA-approved catheter devices as part of a combined i.v./i.a. approach to recanalization as the IMS III study progresses. A secondary objective of the IMS III trial is to determine the cost-effectiveness of the combined i.v./i.a. approach as compared with standard i.v. rt-PA. Trial enrollment began in July of 2006.


METHODS
A projected 900 subjects with moderate-to-large (NIHSS>or=10) ischemic strokes between ages 18 and 80 will be enrolled over the next 5 years at 40-plus centers in the United States and Canada. Patients must have i.v. treatment initiated within 3 h of stroke onset in both arms. Subjects will be randomized in a 2 : 1 ratio with more subjects enrolled in the combined i.v./i.a. group. The i.v. rt-PA alone group will receive the standard full dose [0.9 mg/kg, 90 mg maximum (10% as bolus)] of rt-PA intravenously over an hour. The combined i.v./i.a. group will receive a lower dose of i.v. rt-PA ( approximately 0.6 mg/kg, 60 mg maximum) over 40 min, followed by immediate angiography. If a treatable thrombus is not demonstrated, no i.a. therapy will be administered. If an appropriate thrombus is identified, treatment will continue with either the Concentric Merci thrombus-removal device, infusion of rt-PA and delivery of low-intensity ultrasound at the site of the occlusion via the EKOS Micro-Infusion Catheter, or infusion of rt-PA via a standard microcatheter. If i.a. rt-Pa therapy is the chosen strategy, a maximum of 22 mg of i.a. rt-PA may be given. The choice of i.a. strategy will be made by the treating neurointerventionalist. The i.a. treatment must begin within 5 h and be completed within 7 h of stroke onset.


RESULTS
The primary outcome measure is a favorable clinical outcome, defined as a modified Rankin Scale Score of 0-2 at 3 months. The primary safety measure is mortality at 3 months and symptomatic ICH within the 24 h of randomization.
Khatri
Pooja
P
Department of Neurology, University of Cincinnati, 231 Albert Sabin Way ML 0525, Cincinnati, OH 45267-0525, USA. pooja.khatri@uc.edu
Hill
Michael D
MD
Palesch
Yuko Y
YY
Spilker
Judith
J
Jauch
Edward C
EC
Carrozzella
Janice A
JA
Demchuk
Andrew M
AM
Martin
Renee'
R
Mauldin
Patrick
P
Dillon
Catherine
C
Ryckborst
Karla J
KJ
Janis
Scott
S
Tomsick
Thomas A
TA
Broderick
Joseph P
JP
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008875:Middle Aged; D018579:Patient Selection; D010865:Pilot Projects; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator