Clinical trial NCT00856661: Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke (DIAS-4)
Official title: A Randomised, Double-Blind, Parallel-Group Placebo-Controlled Phase III Study to Evaluate the Efficacy and Safety of Desmoteplase in Subjects With Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Stroke
Keywords: Acute ischemic stroke
Angiography
Desmoteplase
Thrombolytic
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2009-03-06
Enrollment: 270
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 the study is to determine whether desmoteplase is effective and safe in the treatment of patients with acute ischaemic stroke when given within 3 to 9 hours from onset of stroke symptoms.

Detailed description: Acute stroke is a major cause of mortality and long-term disability in the developed world. The only currently approved thrombolytic intervention for acute ischemic stroke, which constitutes the majority of strokes, is alteplase (recombinant tissue plasminogen activator; rtPA). The use of alteplase is limited as it is approved for use within 3 hours after symptom onset and by the risk of inducing intracerebral haemorrhage; consequently fewer than 3% of acute stroke subjects are treated. The thrombolytic agent desmoteplase (recombinant Desmodus Salivary Plasminogen Activator alpha-1; rDSPAalpha-1) produced by recombinant biotechnology has its naturally occurring counterpart in the saliva of the vampire bat Desmodus rotundus. Compared to alteplase, desmoteplase has a more favourable profile in terms of high fibrin specificity and non neurotoxicity.

The study aims to confirm efficacy and safety of desmoteplase for thrombolytic therapy of patients with acute ischaemic stroke in the extended time window of 3 to 9 hours after onset of stroke symptoms.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of acute ischemic stroke
* Informed consent
* Age between 18 and 85 years
* Treatment can be initiated within 3 to 9 hours after the onset of stroke symptoms
* NIHSS Score of 4 to 24
* Vessel occlusion or high-grade stenosis on MRI or CTA in proximal cerebral arteries

Exclusion Criteria:

* Pre-stroke mRS \>1
* Previous exposure to desmoteplase
* Extensive early infarction on MRI or CT in any affected area
* Imaging evidence of ICH or SAH; AV malformation; cerebral aneurysm; or cerebral neoplasm
* Internal carotid artery occlusion on the side of the stroke lesion
* Treatment with heparin in the past 48 hours and a prolonged partial thromboplastin time
* Treatment with oral anticoagulants and a prolonged prothrombin time
* Treatment with glycoprotein IIb - IIIa inhibitors within the past 72 hours. Use of single agent oral platelet inhibitors is permitted
* Treatment with a thrombolytic agent within the past 72 hours

Primary outcomes:
measure: Modified Rankin Scale Score (mRS) (Percentage of Participants With mRS Scores 0-2)
timeFrame: Day 90
Secondary outcomes:
measure: National Institutes of Health Stroke Scale (NIHSS) Score. (Percentage of Participants With NIHSS Scores <=1 or NIHSS Decrease >=8)
timeFrame: 90 days
measure: Composite of mRS & NIHSS Response (Percentage of Participants With mRS Scores 0-2 and (NIHSS <= 1 or NIHSS Decrease >= 8)
timeFrame: Day 90
measure: Modified Ranking Scale Score (Using the Ordinal Scale)
timeFrame: Day 90
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: US053
state: Arizona
city: Castro Valley
country: United States
facility: US081
state: California
city: La Jolla
country: United States
facility: US089
state: California
city: Loma Linda
country: United States
facility: US043
state: California
city: Los Angeles
country: United States
facility: US008
state: California
city: Palo Alto
country: United States
facility: US020
state: California
city: Pasadena
country: United States
facility: US050
state: California
city: Santa Barbara
country: United States
facility: US098
state: California
city: Thousand Oaks
country: United States
facility: US051
state: California
city: Englewood
country: United States
facility: US068
state: Colorado
city: Fairfield
country: United States
facility: US063
state: Connecticut
city: New Haven
country: United States
facility: US104
state: Connecticut
city: Pensacola
country: United States
facility: US049
state: Florida
city: Atlanta
country: United States
facility: US109
state: Georgia
city: Augusta
country: United States
facility: US042
state: Georgia
city: Columbus
country: United States
facility: US052
state: Georgia
city: Decatur
country: United States
facility: US080
state: Georgia
city: Lawrenceville
country: United States
facility: US040
state: Georgia
city: Macon
country: United States
facility: US067
state: Georgia
city: Savannah
country: United States
facility: US085
state: Georgia
city: Savannah
country: United States
facility: US086
state: Georgia
city: Chicago
country: United States
facility: US093
state: Illinois
city: Chicago
country: United States
facility: US101
state: Illinois
city: Chicago
country: United States
facility: US044
state: Illinois
city: Evanston
country: United States
facility: US074
state: Illinois
city: Glenview
country: United States
facility: US073
state: Illinois
city: Maywood
country: United States
facility: US091
state: Illinois
city: Oak Lawn
country: United States
facility: US088
state: Illinois
city: Indianapolis
country: United States
facility: US016
state: Indiana
city: Des Moines
country: United States
facility: US072
state: Iowa
city: New Orleans
country: United States
facility: US061
state: Louisiana
city: New Orleans
country: United States
facility: US108
state: Louisiana
city: Shreveport
country: United States
facility: US064
state: Louisiana
city: Baltimore
country: United States
facility: US014
state: Maryland
city: Boston
country: United States
facility: US039
state: Massachusetts
city: Boston
country: United States
facility: US003
state: Massachusetts
city: Worcester
country: United States
facility: US017
state: Massachusetts
city: Detroit
country: United States
facility: US066
state: Michigan
city: Detroit
country: United States
facility: US096
state: Michigan
city: Detroit
country: United States
facility: US083
state: Michigan
city: Grand Blanc
country: United States
facility: US060
state: Michigan
city: Grand Rapids
country: United States
facility: US078
state: Michigan
city: Kalamazoo
country: United States
facility: US103
state: Michigan
city: Petoskey
country: United States
facility: US056
state: Michigan
city: Royal Oak
country: United States
facility: US113
state: Michigan
city: Southfield
country: United States
facility: US076
state: Michigan
city: Southfield
country: United States
facility: US082
state: Michigan
city: Troy
country: United States
facility: US079
state: Michigan
city: Gulfport
country: United States
facility: US059
state: Mississippi
city: Springfield
country: United States
facility: US048
state: Missouri
city: Lebanon
country: United States
facility: US077
state: New Hampshire
city: Edison
country: United States
facility: US055
state: New Jersey
city: Neptune
country: United States
facility: US115
state: New Jersey
city: Ridgewood
country: United States
facility: US100
state: New Jersey
city: Albany
country: United States
facility: US075
state: New York
city: Brooklyn
country: United States
facility: US102
state: New York
city: Buffalo
country: United States
facility: US012
state: New York
city: Stony Brook
country: United States
facility: US026
state: New York
city: Greensboro
country: United States
facility: US037
state: North Carolina
city: Winston-Salem
country: United States
facility: US069
state: North Carolina
city: Cleveland
country: United States
facility: US038
state: Ohio
city: Columbus
country: United States
facility: US001
state: Ohio
city: Columbus
country: United States
facility: US062
state: Ohio
city: Toledo
country: United States
facility: US046
state: Ohio
city: Springfield
country: United States
facility: US095
state: Oregon
city: Allentown
country: United States
facility: US070
state: Pennsylvania
city: Philadelphia
country: United States
facility: US023
state: Pennsylvania
city: Pittsburg
country: United States
facility: US099
state: Pennsylvania
city: Pittsburg
country: United States
facility: US084
state: Pennsylvania
city: Providence
country: United States
facility: US092
state: Rhode Island
city: Warwick
country: United States
facility: US087
state: Rhode Island
city: Columbia
country: United States
facility: US057
state: South Carolina
city: Chattanooga
country: United States
facility: US019
state: Tennessee
city: Nashville
country: United States
facility: US058
state: Tennessee
city: Houston
country: United States
facility: US021
state: Texas
city: Houston
country: United States
facility: US031
state: Texas
city: Houston
country: United States
facility: US112
state: Texas
city: Richmond
country: United States
facility: US047
state: Virginia
city: Winchester
country: United States
facility: US006
state: Virginia
city: Madison
country: United States
facility: US011
state: Wisconsin
city: Milwaukee
country: United States
facility: US097
state: Wisconsin
city: Brugge
country: Belgium
facility: BE008
city: Hasselt
country: Belgium
facility: BE004
city: Roeselare
country: Belgium
facility: BE005
city: Wilrijk
country: Belgium
facility: BE006
city: Campinas
country: Brazil
facility: BR012
city: Porto Alegre
country: Brazil
facility: BR004
city: Porto Alegre
country: Brazil
facility: BR008
city: Porto Alegre
country: Brazil
facility: BR007
city: Rio de Janeiro
country: Brazil
facility: BR009
city: Rio de Janeiro
country: Brazil
facility: BR011
city: Salvador
country: Brazil
facility: BR006
city: Calgary
country: Canada
facility: CA001
state: Alberta
city: Edmonton
country: Canada
facility: CA004
city: Halifax
country: Canada
facility: CA006
city: Mississauga
country: Canada
facility: CA008
city: Ottawa
country: Canada
facility: CA007
city: Toronto
country: Canada
facility: CA012
city: Toronto
country: Canada
facility: CA002
city: Victoria
country: Canada
facility: CA005
city: Santiago
country: Chile
facility: CL002
city: Santiago
country: Chile
facility: CL003
city: Santiago
country: Chile
facility: CL004
city: Santiago
country: Chile
facility: CL006
city: Valparaiso
country: Chile
facility: CL005
city: Aalborg
country: Denmark
facility: DK002
city: Aarhus
country: Denmark
facility: DK001
city: Copenhagen NV
country: Denmark
facility: DK004
city: Glostrup
country: Denmark
facility: DK003
city: Helsinki
country: Finland
facility: FI001
city: Tampere
country: Finland
facility: FI002
city: Turku
country: Finland
facility: FI003
city: Dublin
country: Ireland
facility: IE001
city: Ancona
country: Italy
facility: IT010
city: Brescia
country: Italy
facility: IT008
city: Firenze
country: Italy
facility: IT003
city: Imperia
country: Italy
facility: IT004
city: Milano
country: Italy
facility: IT002
city: Milano
country: Italy
facility: IT006
city: Milano
country: Italy
facility: IT009
city: Modena
country: Italy
facility: IT012
city: Rome
country: Italy
facility: IT001
city: Rome
country: Italy
facility: IT005
city: Rozzano
country: Italy
facility: IT007
city: Verona
country: Italy
facility: IT011
city: D.f.
country: Mexico
facility: MX002
city: Mexico City
country: Mexico
facility: MX003
city: Mexico City
country: Mexico
facility: MX004
city: Monterrey Nuevo Leon
country: Mexico
facility: MX005
city: Bergen
country: Norway
facility: NO003
city: Oslo
country: Norway
facility: NO001
city: Trondheim
country: Norway
facility: NO002
city: Cape Town
country: South Africa
facility: ZA003
city: Cape Town
country: South Africa
facility: ZA002
city: Cape Town
country: South Africa
facility: ZA001
city: Lund
country: Sweden
facility: SE002
city: Malmø
country: Sweden
facility: SE001
city: Belfast
country: United Kingdom
facility: GB012
city: Christchurch
country: United Kingdom
facility: GB004
city: Dundee
country: United Kingdom
facility: GB010
city: Exeter
country: United Kingdom
facility: GB002
city: Glasgow
country: United Kingdom
facility: GB009
city: Glasgow
country: United Kingdom
facility: GB007
city: Liverpool
country: United Kingdom
facility: GB011
city: London
country: United Kingdom
facility: GB006
city: London
country: United Kingdom
facility: GB003
city: Newcastle upon Tyne
country: United Kingdom
facility: GB001
city: Nottingham
country: United Kingdom
facility: GB016
city: Sheffield
country: United Kingdom
facility: GB014
city: Stoke on Trent
country: United Kingdom
facility: GB005
city: Westcliff-on-Sea
country: United Kingdom
facility: GB015
city: Wolverhampton
country: United Kingdom
facility: GB013
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References:
citation: von Kummer R, Mori E, Truelsen T, Jensen JS, Gronning BA, Fiebach JB, Lovblad KO, Pedraza S, Romero JM, Chabriat H, Chang KC, Davalos A, Ford GA, Grotta J, Kaste M, Schwamm LH, Shuaib A, Albers GW; DIAS-4 Investigators. Desmoteplase 3 to 9 Hours After Major Artery Occlusion Stroke: The DIAS-4 Trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke). Stroke. 2016 Dec;47(12):2880-2887. doi: 10.1161/STROKEAHA.116.013715. Epub 2016 Nov 1.