DESMOTEPLASE (INN) IN ACUTE ISCHAEMIC STROKE: PHASE III; A prospective, randomised, double-blind, placebo-controlled, single bolus, multinational, multi-centre, parallel group, dose ranging study of desmoteplase (INN) in the indication of acute stroke - DIAS-2

• Conditions: acute ischaemic stroke; MedDRA version: 8.1Level: LLTClassification code 10061256Term: Ischaemic stroke

• Registration Number: EUCTR2005-000421-34-FI
• Lead Sponsor: PAION Deutschland GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-04-26
• Last Update Posted: 1 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 196

Inclusion Criteria

1.Informed Consent (all sites) and HIPAA authorization (US sites only)
2.Age 18 – 85 years
3.Treatment onset within 3 - 9 hours after onset of stroke symptomsIf the exact onset of stroke is unclear, but the onset of stroke symptoms was less than 8 hours before arrival at the hospital, then the patient can be considered eligible for the study (this provides 1 hour for eligibility determination prior to receipt of randomized therapy). All measures should be taken so that treatment with alteplase within 3 hours of symptom onset is not delayed in patients who qualify for receiving alteplase.
4.Score of 4 - 24 on the NIHSS with clinical signs of hemispheric infarction (e.g. hemiparesis) suggestive of ischemic stroke

Inclusion Criterion from diagnostic imaging screening:A 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Previous participation in a desmoteplase study (i.e., DEEP, DIAS, DEDAS, DEPTH).
2.Participation in any investigational study in the previous 30 days.
3.Any terminal illness that is serious or advanced (patient is not expected to survive more than 1 year).
4.Any condition that could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study (this applies to patients with severe microangiopathy such as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura)The judgment is left to the discretion of the Investigator.
5.Patients not able to receive study medication within 60 minutes after completion of diagnostic imaging screening.
6.Pregnant women (positive serum ßHCG pregnancy test, positive urine pregnancy test or clinically evident pregnancy).
7.Rapidly improving neurological symptoms such that the rate of improvement is projected to give the patient an NIHSS score of < 4 at randomization.
8.Pre-stroke MRS score of > 1 (indicating previous disability).
8.1.Consciousness level > 2 on question 1a of NIHSS
9.History or clinical presentation of ICH, subarachnoid hemorrhage (SAH), arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm. Patients with incidental small intracranial aneurysm can be considered for the study if the aneurysm is < 5 mm, not thrombosed, and not visibly bleeding.
10.Suspected acute vertebral or basilar artery occlusion.
11.Current use of oral anticoagulants and a prolonged prothrombin time (INR > 1.6).
12.Use of heparin, except for low dose subcutaneous heparin, in the previous 48 hours and a prolonged partial thromboplastin time exceeding the upper limit of the local laboratory normal range.
13.Use of glycoprotein IIb - IIIa inhibitors within the past 72 hours. Use of single agent oral platelet inhibitors (clopidogrel or low-dose aspirin) prior to study entry is permitted.
14.Baseline platelet count < 100,000/mm³.
15.Baseline hematocrit of < 0.25.
16.Baseline blood glucose < 50 mg/dl or > 300 mg/dl (< 3 mmol/l or > 17 mmol/l). Patients with blood glucose value between 200-300 mg/dL can be considered for the study only if the blood glucose value decreases to < 200 mg/dl after antidiabetic treatment and before administration of study medication.
17.Uncontrolled hypertension defined by a blood pressure > 185 mmHg systolic or >110 mmHg diastolic on at least 2 separate occasions at least 10 minutes apart, or requiring aggressive treatment to reduce the blood pressure within the limitsThe definition of aggressive treatment” is left to the discretion of the responsible Investigator.
18.Hereditary or acquired hemorrhagic diathesis.
19.Gastrointestinal or urinary bleeding within the preceding 21 days.
20.Arterial puncture at a non-compressible site within the previous 7 days.
21.Another stroke or a serious head injury in the previous 6 weeks.
22.Any history of prior stroke in a patient with diabetes unless the blood glucose is within the range indicated above.
23.Major surgery within the preceding 14 days.
24.Seizure at the onset of stroke.
25.Acute myocardial infarction (AMI) within the previous 3 weeks.
26.Exposure to a thrombolytic within the previous 72 hours.
27.Any intracranial pathology that would interfere with the assessment of the chosen imaging technique for screeningExclusion criteria from diagnostic imaging screening:
28.Extensive early infarction in any affected area defined by an infarcted core involving >1/3 of MCA territory or t

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Main objective : The study objective is to further investigate the clinical efficacy and safety of two doses of desmoteplase (90 µg/kg and 125 µg/kg) administered as a single intravenous bolus to patients with acute ischaemic stroke within 3 – 9 hours after onset of symptoms. ;Secondary Objective: ;Primary end point(s): The primary efficacy parameter is clinical improvement at Day 90 defined for each patient as achievement of all three of the following: (1) Improvement of > = 8 points from baseline on the National Institutes of Health Stroke Scale (NIHSS) (or NIHSS score < = 1), (2) Modified Rankin Scale (MRS) score of 0 – 2, and (3) Barthel Index (BI) score of 100 – 75.