Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke (DIAS-3)

• ClinicalTrials.gov Identifier: NCT00790920
• Recruitment Status: Completed
• First Posted: November 14, 2008
• Last Update Posted: September 18, 2015
• Sponsor: H. Lundbeck A/S
• Information provided by (Responsible Party): H. Lundbeck A/S

Tracking Information

• First Submitted Date: November 13, 2008
• First Posted Date: November 14, 2008
• Last Update Posted Date: September 18, 2015
• Study Start Date: December 2008
• Actual Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 13, 2008): Modified Rankin Scale Score [ Time Frame: 90 days ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: November 13, 2008): National Institutes of Health Stroke Scale (NIHSS) Score [ Time Frame: 90 days ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke
• 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
• 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 3-9 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 3-9 hours after onset of stroke symptoms.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Stroke

Intervention

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

Study Arms

• Experimental: Desmoteplase
  Intervention: Drug: Desmoteplase
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Albers GW, von Kummer R, Truelsen T, Jensen JK, Ravn GM, Gronning BA, Chabriat H, Chang KC, Davalos AE, Ford GA, Grotta J, Kaste M, Schwamm LH, Shuaib A; DIAS-3 Investigators. Safety and efficacy of desmoteplase given 3-9 h after ischaemic stroke in patients with occlusion or high-grade stenosis in major cerebral arteries (DIAS-3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet Neurol. 2015 Jun;14(6):575-84. doi: 10.1016/S1474-4422(15)00047-2. Epub 2015 Apr 30.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 17, 2015): 492
• Original Estimated Enrollment (submitted: November 13, 2008): 320
• Study Completion Date: Not Provided
• Actual Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of acute ischemic stroke
• Informed consent
• Age between 18 and 85 years
• Treatment can be initiated within 3-9 hours after the onset of stroke symptoms
• NIHSS Score of 4-24
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Estonia, France, Germany, Hong Kong, India, Korea, Republic of, Netherlands, Philippines, Poland, Singapore, Spain, Switzerland, Taiwan, Thailand, Vietnam

Administrative Information

• NCT Number: NCT00790920
• Other Study ID Numbers: 12402A; 2008-000622-40 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: H. Lundbeck A/S
• Original Responsible Party: Same as current
• Current Study Sponsor: H. Lundbeck A/S
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Email contact via H. Lundbeck A/S; LundbeckClinicalTrials@lundbeck.com

• PRS Account: H. Lundbeck A/S
• Verification Date: September 2015