Clinical trial NCT00111852: Study of Desmoteplase (International Nonproprietary Name [INN]) in Acute Ischemic Stroke (DIAS-2)
Official title: A Prospective, Randomized, Double-blind, Placebo-controlled, Single Bolus, Multinational, Multi-center, Parallel Group, Dose-ranging Study of Desmoteplase (INN) in the Indication of Acute Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Stroke, Acute
Keywords: Desmoteplase
Acute Ischemic Stroke
Stroke, Acute
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
First posted: 2005-05-27
Enrollment: 193
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate desmoteplase (which is a manufactured protein derived from the saliva of the vampire bat) in dissolving clots that are blocking the flow of blood through one (or more) of the blood vessels supplying the brain, thereby reopening the blocked blood vessel and allowing blood to flow again in individuals suffering from ischemic stroke.


Eligibility criteria: Inclusion Criteria:

* Eligible for study treatment within 3-9 hours after onset of stroke symptoms.
* Score of 4-24 on the NIHSS with clinical signs of hemispheric infarction (i.e. hemiparesis) suggestive of ischemic stroke.

Inclusion Criteria from diagnostic imaging screening:

* Distinct penumbra (at least 20%), measured by MRI (PWI/DWI) or perfusion CT, related to middle cerebral artery (MCA), anterior cerebral artery (ACA), or posterior cerebral artery (PCA) territory in a hemispheric distribution.

Exclusion Criteria:

* History or clinical presentation of intracranial hemorrhage (ICH), subarachnoid hemorrhage, arteriovenous malformation, aneurysm, or cerebral neoplasm.
* Rapidly improving neurological symptoms.
* Pre-stroke MRS score of \> 1 (including previous disability).
* Suspected acute vertebral or basilar artery occlusion.
* Current use of anticoagulants and a prolonged prothrombin time.
* Uncontrolled hypertension.
* Baseline hematocrit of \< 0.25.
* Baseline platelet count \< 100,000/mm3.

Primary outcomes:
measure: National Institutes of Health Stroke Scale (NIHSS)
timeFrame: Change from Baseline to day 90
measure: Modified Rankin Scale (MRS)
timeFrame: Day 90
measure: Barthel Index (BI) score of 75-100.
timeFrame: Day 90
Secondary outcomes:
measure: Percentage of patients with improvement in NIHSS score
timeFrame: From Baseline to Day 90
measure: Percentage of patients with MRS score of 0-2
timeFrame: Day 90
measure: Percentage of patients with BI score of 75-100
timeFrame: Day 90
measure: Infarct Volume
timeFrame: Change from baseline to Day 30
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Neurological Institute, Dept. of Neurology
state: Alabama
city: Los Angeles
country: United States
facility: University of California Los Angeles Medical Center
state: California
city: Delray Beach
country: United States
facility: Brain Matters, Inc.
state: Florida
city: Melbourne
country: United States
facility: Melbourne Internal Medicine Associates (MIMA)
state: Florida
city: Melbourne
country: United States
facility: Holmes Regional Medical Center
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana Neuroscience Institute
state: Indiana
city: Louisville
country: United States
facility: Jewish Hospital Healthcare Services, Inc.
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Hospital
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (BIDMC)
state: Massachusetts
city: Las Vegas
country: United States
facility: Nevada Neurosciences Institute at Sunrise
state: Nevada
city: Edison
country: United States
facility: JFK Medical Center
state: New Jersey
city: Charlotte
country: United States
facility: Presbyterian Hospital
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Chattanooga
country: United States
facility: Erlanger Health System
state: Tennessee
city: Chattanooga
country: United States
facility: University of Tennessee, College of Medicine
state: Tennessee
city: Nashville
country: United States
facility: Saint Thomas Hospital
state: Tennessee
city: Dallas
country: United States
facility: University of Texas, Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
city: Winchester
country: United States
facility: Winchester Medical Center
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: New Lambton Heights
country: Australia
facility: John Hunter Hospital
city: Victoria
country: Australia
facility: Box Hill Hospital
city: Woodville
country: Australia
facility: Queen Elizabeth Hospital
city: Graz
country: Austria
facility: Medizinische Universitat Graz
city: Innsbruck
country: Austria
facility: Leopold-Franzens-Universitat Innsbruck
city: Linz
country: Austria
facility: O O Landesnervenklinik Wagner-Jauregg
city: Edmonton
country: Canada
facility: Walter Mackenzie Health Sciences Centre
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Bonn
country: Germany
facility: Neurologische Universitatsklinik
city: Leipzig
country: Germany
facility: Klinik und Poliklinik der Universitat Leipzig
city: Ulm
country: Germany
facility: Neurologische Klinik Universitat Ulm
city: Amsterdam
country: Netherlands
facility: University Hospital Amsterdam Department Neurology
city: Badalona
country: Spain
facility: University Hospital Germans Trias i Pujol
city: Girona
country: Spain
facility: Hospital Universitari Doctor Josep Trueta
Study officials:
affiliation: Forest Laboratories
name: Leslie Lipka, MD
role: STUDY_DIRECTOR
References:
citation: Warach S, Al-Rawi Y, Furlan AJ, Fiebach JB, Wintermark M, Lindsten A, Smyej J, Bharucha DB, Pedraza S, Rowley HA. Refinement of the magnetic resonance diffusion-perfusion mismatch concept for thrombolytic patient selection: insights from the desmoteplase in acute stroke trials. Stroke. 2012 Sep;43(9):2313-8. doi: 10.1161/STROKEAHA.111.642348. Epub 2012 Jun 26.
citation: Fiebach JB, Al-Rawi Y, Wintermark M, Furlan AJ, Rowley HA, Lindsten A, Smyej J, Eng P, Warach S, Pedraza S. Vascular occlusion enables selecting acute ischemic stroke patients for treatment with desmoteplase. Stroke. 2012 Jun;43(6):1561-6. doi: 10.1161/STROKEAHA.111.642322. Epub 2012 Apr 3.
citation: Hacke W, Furlan AJ, Al-Rawi Y, Davalos A, Fiebach JB, Gruber F, Kaste M, Lipka LJ, Pedraza S, Ringleb PA, Rowley HA, Schneider D, Schwamm LH, Leal JS, Sohngen M, Teal PA, Wilhelm-Ogunbiyi K, Wintermark M, Warach S. Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion-diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2009 Feb;8(2):141-50. doi: 10.1016/S1474-4422(08)70267-9. Epub 2008 Dec 25.