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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00856661
Recruitment Status : Terminated (The recruitment into DIAS4 has been stopped as the result of DIAS 3 indicates that the study is unlikely to reach its primary endpoint with the current protocol)
First Posted : March 6, 2009
Results First Posted : December 22, 2015
Last Update Posted : March 16, 2017
Sponsor:
Information provided by (Responsible Party):
H. Lundbeck A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Stroke
Interventions Drug: Desmoteplase
Drug: Placebo
Enrollment 270
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Desmoteplase Placebo
Hide Arm/Group Description 90 μg/kg bodyweight, IV, single bolus over 1 to 2 minutes 3-9 hours after symptoms onset Placebo: IV, single bolus over 1 to 2 minutes 3-9 hours after symptoms onset
Period Title: Overall Study
Started 135 [1] 135 [1]
Treated 126 131
Randomized Not Treated 9 4
Completed 108 106
Not Completed 27 29
Reason Not Completed
Death             15             18
Protocol Violation             2             1
Withdrawal by Subject             1             2
Lost to Follow-up             1             3
Physician Judgement             8             5
[1]
Randomised
Arm/Group Title Desmoteplase Placebo Total
Hide Arm/Group Description Desmoteplase: 90 μg/kg bodyweight, IV, single bolus over 1 to 2 minutes 3-9 hours after symptoms onset Placebo: IV, single bolus over 1 to 2 minutes 3-9 hours after symptoms onset Total of all reporting groups
Overall Number of Baseline Participants 135 135 270
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 135 participants 135 participants 270 participants
69.1  (11.1) 68.2  (12.5) 68.6  (11.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 135 participants 135 participants 270 participants
Female
72
  53.3%
69
  51.1%
141
  52.2%
Male
63
  46.7%
66
  48.9%
129
  47.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 135 participants 135 participants 270 participants
White 111 115 226
Black or african americal 11 9 20
Asian 7 6 13
Other 6 5 11
1.Primary Outcome
Title Modified Rankin Scale Score (mRS) (Percentage of Participants With mRS Scores 0-2)
Hide Description 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
Time Frame Day 90
Hide Outcome Measure Data
Hide Analysis Population Description
Two and three patients from the desmoteplase and placebo group, respectively, had no valid functional assessment done. Hence, the full analysis set consisted of 124 and 128 patients, respectively.
Arm/Group Title Desmoteplase Placebo
Hide Arm/Group Description:
Desmoteplase: 90 μg/kg bodyweight, IV, single bolus over 1 to 2 minutes 3-9 hours after symptoms onset
Placebo: IV, single bolus over 1 to 2 minutes 3-9 hours after symptoms onset
Overall Number of Participants Analyzed 124 128
Measure Type: Number
Unit of Measure: Percentage of participants
41.9 35.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Desmoteplase, Placebo
Comments All patients who were treated and had at least one valid post-baseline assessment of the mRS. As death is a valid outcome on the mRS, patients who died within 90 days after IMP administration were included.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2290
Comments [Not Specified]
Method Regression, Logistic
Comments If no assessment was available for last observation carried forward after baseline, the mRS score was set to 5 if alive, or 6, if otherwise = death
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.45
Confidence Interval (2-Sided) 95%
0.79 to 2.64
Estimation Comments [Not Specified]
2.Secondary Outcome
Title National Institutes of Health Stroke Scale (NIHSS) Score. (Percentage of Participants With NIHSS Scores <=1 or NIHSS Decrease >=8)
Hide Description 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.
Time Frame 90 days
Hide Outcome Measure Data
Hide Analysis Population Description
Two and three patients from the desmoteplase and placebo group, respectively, had no valid functional assessment done. Hence, the full analysis set consisted of 124 and 128 patients, respectively.
Arm/Group Title Desmoteplase Placebo
Hide Arm/Group Description:
Desmoteplase: 90 μg/kg bodyweight, IV, single bolus over 1 to 2 minutes 3-9 hours after symptoms onset
Placebo: IV, single bolus over 1 to 2 minutes 3-9 hours after symptoms onset
Overall Number of Participants Analyzed 124 128
Measure Type: Number
Unit of Measure: Percentage of participants
49.2 50.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Desmoteplase, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9401
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.59 to 1.62
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Composite of mRS & NIHSS Response (Percentage of Participants With mRS Scores 0-2 and (NIHSS <= 1 or NIHSS Decrease >= 8)
Hide Description Please see outcomes measure one and two for detailed description of the scales
Time Frame Day 90
Hide Outcome Measure Data
Hide Analysis Population Description
Two and three patients from the desmoteplase and placebo group, respectively, had no valid functional assessment done. Hence, the full analysis set consisted of 124 and 128 patients, respectively.
Arm/Group Title Desmoteplase Placebo
Hide Arm/Group Description:
Desmoteplase: 90 μg/kg bodyweight, IV, single bolus over 1 to 2 minutes 3-9 hours after symptoms onset
Placebo: IV, single bolus over 1 to 2 minutes 3-9 hours after symptoms onset
Overall Number of Participants Analyzed 124 128
Measure Type: Number
Unit of Measure: Percentage of participants
32.3 28.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Desmoteplase, Placebo
Comments All patients treated, who had at least one valid post-baseline assessment of the mRS and with a baseline NIHSS score of 8 to 24. If no assessment was available for last observation carried forward after baseline, the mRS score was set to 5 if the patient was known to be alive, or 6, if otherwise = dead.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5076
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.22
Confidence Interval (2-Sided) 95%
0.68 to 2.18
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Modified Ranking Scale Score (Using the Ordinal Scale)
Hide Description Please see outcomes measure one for detailed description of the mRS scale
Time Frame Day 90
Hide Outcome Measure Data
Hide Analysis Population Description
Two and three patients from the desmoteplase and placebo group, respectively, had no valid functional assessment done. Hence, the full analysis set consisted of 124 and 128 patients, respectively.
Arm/Group Title Desmoteplase Placebo
Hide Arm/Group Description:
Desmoteplase: 90 μg/kg bodyweight, IV, single bolus over 1 to 2 minutes 3-9 hours after symptoms onset
Placebo: IV, single bolus over 1 to 2 minutes 3-9 hours after symptoms onset
Overall Number of Participants Analyzed 124 128
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
3.02  (0.14) 3.12  (0.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Desmoteplase, Placebo
Comments all patients treated, who had at least one valid post-baseline assessment of the mRS. As death is a valid outcome on the mRS, patients who died within 90 days after IMP administration were included
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6146
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.72 to 1.75
Estimation Comments [Not Specified]
Time Frame baseline to end of study
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Desmoteplase
Hide Arm/Group Description Placebo: IV, single bolus over 1 to 2 minutes 3-9 hours after symptoms onset Desmoteplase: 90 ug/kg, IV, single bolus over 1 to 2 minutes 3-9 hours after symptoms onset
All-Cause Mortality
Placebo Desmoteplase
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Desmoteplase
Affected / at Risk (%) Affected / at Risk (%)
Total   56/131 (42.75%)   61/126 (48.41%) 
Blood and lymphatic system disorders     
Anaemia of chronic disease  1  0/131 (0.00%)  1/126 (0.79%) 
Coagulopathy  1  1/131 (0.76%)  0/126 (0.00%) 
Deficiency anaemia  1  0/131 (0.00%)  2/126 (1.59%) 
Iron deficiency anaemia  1  0/131 (0.00%)  1/126 (0.79%) 
Leukopenia  1  0/131 (0.00%)  1/126 (0.79%) 
Normochromic normocytic anaemia  1  1/131 (0.76%)  1/126 (0.79%) 
Pernicious anaemia  1  0/131 (0.00%)  1/126 (0.79%) 
Cardiac disorders     
Acute myocardial infarction  1  1/131 (0.76%)  2/126 (1.59%) 
Atrial fibrillation  1  4/131 (3.05%)  4/126 (3.17%) 
Bradycardia  1  1/131 (0.76%)  2/126 (1.59%) 
Cardiac arrest  1  1/131 (0.76%)  2/126 (1.59%) 
Cardiac failure  1  0/131 (0.00%)  2/126 (1.59%) 
Cardiac failure congestive  1  2/131 (1.53%)  0/126 (0.00%) 
Cardiac tamponade  1  0/131 (0.00%)  1/126 (0.79%) 
Cardiomyopathy  1  0/131 (0.00%)  1/126 (0.79%) 
Left ventricular dysfunction  1  1/131 (0.76%)  0/126 (0.00%) 
Mitral valve incompetence  1  1/131 (0.76%)  0/126 (0.00%) 
Sick sinus syndrome  1  1/131 (0.76%)  0/126 (0.00%) 
Tachycardia  1  0/131 (0.00%)  1/126 (0.79%) 
Ventricular tachycardia  1  2/131 (1.53%)  0/126 (0.00%) 
Eye disorders     
Pupils unequal  1  0/131 (0.00%)  1/126 (0.79%) 
Gastrointestinal disorders     
Abdominal discomfort  1  1/131 (0.76%)  0/126 (0.00%) 
Abdominal pain  1  1/131 (0.76%)  0/126 (0.00%) 
Gastric haemorrhage  1  1/131 (0.76%)  0/126 (0.00%) 
Gastrointestinal haemorrhage  1  1/131 (0.76%)  0/126 (0.00%) 
Haematochezia  1  1/131 (0.76%)  0/126 (0.00%) 
Vomiting  1  0/131 (0.00%)  1/126 (0.79%) 
General disorders     
Catheter site phlebitis  1  0/131 (0.00%)  1/126 (0.79%) 
Death  1 [1]  0/131 (0.00%)  1/126 (0.79%) 
Multi-organ failure  1  1/131 (0.76%)  0/126 (0.00%) 
Hepatobiliary disorders     
Cholangitis  1  0/131 (0.00%)  1/126 (0.79%) 
Cholelithiasis  1  0/131 (0.00%)  1/126 (0.79%) 
Infections and infestations     
Bacterial sepsis  1  1/131 (0.76%)  0/126 (0.00%) 
Bronchopneumonia  1  1/131 (0.76%)  0/126 (0.00%) 
Endocarditis bacterial  1  1/131 (0.76%)  1/126 (0.79%) 
Gastroenteritis  1  0/131 (0.00%)  1/126 (0.79%) 
Lower respiratory tract infection  1  0/131 (0.00%)  1/126 (0.79%) 
Pneumonia  1  1/131 (0.76%)  3/126 (2.38%) 
Pneumonia bacterial  1  4/131 (3.05%)  5/126 (3.97%) 
Pulmonary sepsis  1  1/131 (0.76%)  0/126 (0.00%) 
Pyelonephritis acute  1  0/131 (0.00%)  1/126 (0.79%) 
Sepsis  1  2/131 (1.53%)  0/126 (0.00%) 
Staphylococcal infection  1  1/131 (0.76%)  0/126 (0.00%) 
Urinary tract infection  1  0/131 (0.00%)  1/126 (0.79%) 
Urinary tract infection bacterial  1  0/131 (0.00%)  2/126 (1.59%) 
Urosepsis  1  1/131 (0.76%)  0/126 (0.00%) 
Injury, poisoning and procedural complications     
Hip fracture  1  0/131 (0.00%)  1/126 (0.79%) 
Investigations     
Blood culture positive  1  0/131 (0.00%)  1/126 (0.79%) 
Electrocardiogram abnormal  1  0/131 (0.00%)  1/126 (0.79%) 
Haemoglobin decreased  1  4/131 (3.05%)  2/126 (1.59%) 
Nih stroke scale score increased  1  4/131 (3.05%)  0/126 (0.00%) 
Oxygen saturation decreased  1  0/131 (0.00%)  1/126 (0.79%) 
Platelet count decreased  1  0/131 (0.00%)  1/126 (0.79%) 
Respiratory rate increased  1  0/131 (0.00%)  1/126 (0.79%) 
Metabolism and nutrition disorders     
Dehydration  1  1/131 (0.76%)  0/126 (0.00%) 
Hypoglycaemia  1  0/131 (0.00%)  1/126 (0.79%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cardiac valve fibroelastoma  1  1/131 (0.76%)  0/126 (0.00%) 
Colorectal cancer  1  0/131 (0.00%)  1/126 (0.79%) 
Hepatocellular carcinoma  1  1/131 (0.76%)  0/126 (0.00%) 
Lung adenocarcinoma  1  0/131 (0.00%)  1/126 (0.79%) 
Metastases to central nervous system  1  1/131 (0.76%)  0/126 (0.00%) 
Nervous system disorders     
Basal ganglia haemorrhage  1  0/131 (0.00%)  1/126 (0.79%) 
Brain oedema  1  6/131 (4.58%)  3/126 (2.38%) 
Brain stem stroke  1  0/131 (0.00%)  1/126 (0.79%) 
Carotid artery stenosis  1  0/131 (0.00%)  1/126 (0.79%) 
Cerebral artery occlusion  1  0/131 (0.00%)  1/126 (0.79%) 
Cerebral haemorrhage  1  1/131 (0.76%)  2/126 (1.59%) 
Cerebrovascular accident  1  1/131 (0.76%)  0/126 (0.00%) 
Depressed level of consciousness  1  0/131 (0.00%)  1/126 (0.79%) 
Embolic stroke  1  1/131 (0.76%)  0/126 (0.00%) 
Grand mal convulsion  1  1/131 (0.76%)  0/126 (0.00%) 
Haemorrhage intracranial  1  2/131 (1.53%)  2/126 (1.59%) 
Haemorrhagic transformation stroke  1  0/131 (0.00%)  4/126 (3.17%) 
Intracranial pressure increased  1  0/131 (0.00%)  1/126 (0.79%) 
Ischaemic cerebral infarction  1  0/131 (0.00%)  1/126 (0.79%) 
Ischaemic stroke  1  5/131 (3.82%)  3/126 (2.38%) 
Loss of consciousness  1  0/131 (0.00%)  1/126 (0.79%) 
Neurological decompensation  1  2/131 (1.53%)  0/126 (0.00%) 
Stroke in evolution  1  6/131 (4.58%)  10/126 (7.94%) 
Syncope  1  1/131 (0.76%)  0/126 (0.00%) 
Transient ischaemic attack  1  0/131 (0.00%)  3/126 (2.38%) 
Psychiatric disorders     
Agitation  1  1/131 (0.76%)  0/126 (0.00%) 
Major depression  1  0/131 (0.00%)  2/126 (1.59%) 
Suicidal ideation  1  0/131 (0.00%)  1/126 (0.79%) 
Renal and urinary disorders     
Renal failure acute  1  2/131 (1.53%)  1/126 (0.79%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  2/131 (1.53%)  0/126 (0.00%) 
Aspiration  1  0/131 (0.00%)  1/126 (0.79%) 
Pneumonia aspiration  1  1/131 (0.76%)  0/126 (0.00%) 
Pneumothorax  1  0/131 (0.00%)  1/126 (0.79%) 
Pulmonary embolism  1  3/131 (2.29%)  1/126 (0.79%) 
Pulmonary oedema  1  1/131 (0.76%)  1/126 (0.79%) 
Respiratory acidosis  1  0/131 (0.00%)  1/126 (0.79%) 
Respiratory distress  1  1/131 (0.76%)  1/126 (0.79%) 
Respiratory failure  1  0/131 (0.00%)  3/126 (2.38%) 
Vascular disorders     
Deep vein thrombosis  1  1/131 (0.76%)  1/126 (0.79%) 
Hypotension  1  0/131 (0.00%)  1/126 (0.79%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
[1]
Deaths after end of study (day 167). Only deaths occuring within 90 days of IMP are reported in main study
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Desmoteplase
Affected / at Risk (%) Affected / at Risk (%)
Total   107/131 (81.68%)   98/126 (77.78%) 
Cardiac disorders     
Atrial fibrillation  1  13/131 (9.92%)  11/126 (8.73%) 
Gastrointestinal disorders     
Constipation  1  32/131 (24.43%)  30/126 (23.81%) 
Diarrhoea  1  8/131 (6.11%)  6/126 (4.76%) 
Nausea  1  14/131 (10.69%)  12/126 (9.52%) 
Vomiting  1  13/131 (9.92%)  7/126 (5.56%) 
General disorders     
Oedema peripheral  1  1/131 (0.76%)  11/126 (8.73%) 
Pain  1  7/131 (5.34%)  7/126 (5.56%) 
Pyrexia  1  11/131 (8.40%)  8/126 (6.35%) 
Infections and infestations     
Pneumonia bacterial  1  7/131 (5.34%)  3/126 (2.38%) 
Urinary tract infection  1  4/131 (3.05%)  8/126 (6.35%) 
Urinary tract infection bacterial  1  26/131 (19.85%)  22/126 (17.46%) 
Injury, poisoning and procedural complications     
Fall  1  9/131 (6.87%)  3/126 (2.38%) 
Investigations     
Blood potassium decreased  1  4/131 (3.05%)  8/126 (6.35%) 
Nih stroke scale score increased  1  10/131 (7.63%)  8/126 (6.35%) 
Metabolism and nutrition disorders     
Hypercholesterolaemia  1  12/131 (9.16%)  9/126 (7.14%) 
Hyperglycaemia  1  1/131 (0.76%)  7/126 (5.56%) 
Hypokalaemia  1  20/131 (15.27%)  18/126 (14.29%) 
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  7/131 (5.34%)  9/126 (7.14%) 
Nervous system disorders     
Headache  1  22/131 (16.79%)  22/126 (17.46%) 
Stroke in evolution  1  7/131 (5.34%)  7/126 (5.56%) 
Psychiatric disorders     
Anxiety  1  8/131 (6.11%)  11/126 (8.73%) 
Depressive symptom  1  13/131 (9.92%)  13/126 (10.32%) 
Insomnia  1  11/131 (8.40%)  15/126 (11.90%) 
Renal and urinary disorders     
Haematuria  1  7/131 (5.34%)  6/126 (4.76%) 
Urinary retention  1  8/131 (6.11%)  3/126 (2.38%) 
Vascular disorders     
Hypertension  1  14/131 (10.69%)  16/126 (12.70%) 
Hypotension  1  7/131 (5.34%)  4/126 (3.17%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: study director
Organization: H. Lundbeck A/S
Responsible Party: H. Lundbeck A/S
ClinicalTrials.gov Identifier: NCT00856661     History of Changes
Other Study ID Numbers: 12649A
2008-005539-14 ( EudraCT Number )
First Submitted: March 5, 2009
First Posted: March 6, 2009
Results First Submitted: October 6, 2015
Results First Posted: December 22, 2015
Last Update Posted: March 16, 2017