Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke (DIAS-4)

Stroke Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00856661
• Other study ID #: 12649A
• Secondary ID: 2008-005539-14
• Status: Terminated
• Phase: Phase 3
• First received: March 5, 2009
• Last updated: November 18, 2015
• Start date: April 2009

Study information

• Verified date: November 2015
• Source: H. Lundbeck A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaBelgium: Federal Agency for Medicinal Products and Health ProductsBrazil: Ministry of HealthCanada: Health CanadaChile: Comisión Nacional de Investigación Científica y TecnológicaDenmark: Danish Medicines AgencyFinland: Finnish Medicines AgencyIreland: Irish Medicines BoardItaly: The Italian Medicines AgencyMexico: Ministry of HealthNorway: Norwegian Medicines AgencySouth Africa: Medicines Control CouncilSpain: Agencia Española de Medicamentos y Productos SanitariosSweden: Medical Products AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 270
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Stroke

Intervention

Drug:
• Desmoteplase
90 µg/kg bodyweight, IV, single bolus over 1 to 2 minutes on 1st day
• Placebo
IV, single bolus over 1 to 2 minutes on 1st day

Locations

Country	Name	City	State
Belgium	BE008	Brugge
Belgium	BE004	Hasselt
Belgium	BE005	Roeselare
Belgium	BE006	Wilrijk
Brazil	BR012	Campinas
Brazil	BR004	Porto Alegre
Brazil	BR007	Porto Alegre
Brazil	BR008	Porto Alegre
Brazil	BR009	Rio de Janeiro
Brazil	BR011	Rio de Janeiro
Brazil	BR006	Salvador
Canada	CA001	Calgary	Alberta
Canada	CA004	Edmonton
Canada	CA006	Halifax
Canada	CA008	Mississauga
Canada	CA007	Ottawa
Canada	CA002	Toronto
Canada	CA012	Toronto
Canada	CA005	Victoria
Chile	CL002	Santiago
Chile	CL003	Santiago
Chile	CL004	Santiago
Chile	CL006	Santiago
Chile	CL005	Valparaiso
Denmark	DK002	Aalborg
Denmark	DK001	Aarhus
Denmark	DK004	Copenhagen NV
Denmark	DK003	Glostrup
Finland	FI001	Helsinki
Finland	FI002	Tampere
Finland	FI003	Turku
Ireland	IE001	Dublin
Italy	IT010	Ancona
Italy	IT008	Brescia
Italy	IT003	Firenze
Italy	IT004	Imperia
Italy	IT002	Milano
Italy	IT006	Milano
Italy	IT009	Milano
Italy	IT012	Modena
Italy	IT001	Rome
Italy	IT005	Rome
Italy	IT007	Rozzano
Italy	IT011	Verona
Mexico	MX002	D.f.
Mexico	MX003	Mexico City
Mexico	MX004	Mexico City
Mexico	MX005	Monterrey Nuevo Leon
Norway	NO003	Bergen
Norway	NO001	Oslo
Norway	NO002	Trondheim
South Africa	ZA001	Cape Town
South Africa	ZA002	Cape Town
South Africa	ZA003	Cape Town
Sweden	SE002	Lund
Sweden	SE001	Malmø
United Kingdom	GB012	Belfast
United Kingdom	GB004	Christchurch
United Kingdom	GB010	Dundee
United Kingdom	GB002	Exeter
United Kingdom	GB007	Glasgow
United Kingdom	GB009	Glasgow
United Kingdom	GB011	Liverpool
United Kingdom	GB003	London
United Kingdom	GB006	London
United Kingdom	GB001	Newcastle upon Tyne
United Kingdom	GB016	Nottingham
United Kingdom	GB014	Sheffield
United Kingdom	GB005	Stoke on Trent
United Kingdom	GB015	Westcliff-on-Sea
United Kingdom	GB013	Wolverhampton
United States	US075	Albany	New York
United States	US070	Allentown	Pennsylvania
United States	US109	Atlanta	Georgia
United States	US042	Augusta	Georgia
United States	US014	Baltimore	Maryland
United States	US003	Boston	Massachusetts
United States	US039	Boston	Massachusetts
United States	US102	Brooklyn	New York
United States	US012	Buffalo	New York
United States	US081	Castro Valley	California
United States	US019	Chattanooga	Tennessee
United States	US044	Chicago	Illinois
United States	US093	Chicago	Illinois
United States	US101	Chicago	Illinois
United States	US038	Cleveland	Ohio
United States	US057	Columbia	South Carolina
United States	US001	Columbus	Ohio
United States	US052	Columbus	Georgia
United States	US062	Columbus	Ohio
United States	US080	Decatur	Georgia
United States	US072	Des Moines	Iowa
United States	US066	Detroit	Michigan
United States	US083	Detroit	Michigan
United States	US096	Detroit	Michigan
United States	US055	Edison	New Jersey
United States	US068	Englewood	Colorado
United States	US074	Evanston	Illinois
United States	US063	Fairfield	Connecticut
United States	US073	Glenview	Illinois
United States	US060	Grand Blanc	Michigan
United States	US078	Grand Rapids	Michigan
United States	US037	Greensboro	North Carolina
United States	US059	Gulfport	Mississippi
United States	US021	Houston	Texas
United States	US031	Houston	Texas
United States	US112	Houston	Texas
United States	US016	Indianapolis	Indiana
United States	US103	Kalamazoo	Michigan
United States	US089	La Jolla	California
United States	US040	Lawrenceville	Georgia
United States	US077	Lebanon	New Hampshire
United States	US043	Loma Linda	California
United States	US008	Los Angeles	California
United States	US067	Macon	Georgia
United States	US011	Madison	Wisconsin
United States	US091	Maywood	Illinois
United States	US097	Milwaukee	Wisconsin
United States	US058	Nashville	Tennessee
United States	US115	Neptune	New Jersey
United States	US104	New Haven	Connecticut
United States	US061	New Orleans	Louisiana
United States	US108	New Orleans	Louisiana
United States	US088	Oak Lawn	Illinois
United States	US020	Palo Alto	California
United States	US050	Pasadena	California
United States	US049	Pensacola	Florida
United States	US056	Petoskey	Michigan
United States	US023	Philadelphia	Pennsylvania
United States	US053	Phoenix	Arizona
United States	US084	Pittsburg	Pennsylvania
United States	US099	Pittsburg	Pennsylvania
United States	US092	Providence	Rhode Island
United States	US047	Richmond	Virginia
United States	US100	Ridgewood	New Jersey
United States	US113	Royal Oak	Michigan
United States	US098	Santa Barbara	California
United States	US085	Savannah	Georgia
United States	US086	Savannah	Georgia
United States	US064	Shreveport	Louisiana
United States	US076	Southfield	Michigan
United States	US082	Southfield	Michigan
United States	US048	Springfield	Missouri
United States	US095	Springfield	Oregon
United States	US026	Stony Brook	New York
United States	US051	Thousand Oaks	California
United States	US046	Toledo	Ohio
United States	US079	Troy	Michigan
United States	US087	Warwick	Rhode Island
United States	US006	Winchester	Virginia
United States	US069	Winston-Salem	North Carolina
United States	US017	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
H. Lundbeck A/S

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Canada,  Chile,  Denmark,  Finland,  Ireland,  Italy,  Mexico,  Norway,  South Africa,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modified Rankin Scale Score (mRS) (Percentage of Participants With mRS Scores 0-2)	The mRS is a clinician-rated scale designed to provide a global assessment of the patients dependency after stroke. The scale consists of a single item measuring the patient's function based on the ability to perform daily activities. The patient is rated on a 7-point scale from 0 to 6, where a score of 5 corresponds to severe disability, and 6 to death. Assessment of a pre-stroke mRS score is based on an interview addressing the status of the patient prior to the stroke	Day 90	No
Secondary	National Institutes of Health Stroke Scale (NIHSS) Score. (Percentage of Participants With NIHSS Scores <=1 or NIHSS Decrease >=8)	The NIHSS is a clinician-rated, 15-item scale designed to assess the severity of stroke-related neurological deficits: level of consciousness, eye movements, visual fields, facial symmetry, motor strength (arm and leg), coordination, sensation, language (aphasia and dysarthria), and neglect. Each item is rated on a 3-, 4-, or 5-point scale ranging from 0 (normal) to the maximum score (extremely severe symptoms). The total score of the 15 items ranges from 0 to 42, where lower scores indicate less impairment.	90 days	No
Secondary	Composite of mRS & NIHSS Response (Percentage of Participants With mRS Scores 0-2 and (NIHSS <= 1 or NIHSS Decrease >= 8)	Please see outcomes measure one and two for detailed description of the scales	Day 90	No
Secondary	Modified Ranking Scale Score (Using the Ordinal Scale)	Please see outcomes measure one for detailed description of the mRS scale	Day 90	No