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

• Sponsor: H. Lundbeck A/S (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00856661
• Collaborator: (none)
• Enrollment: 270
• Locations: 152
• Arms: 2
• Patients Per Site: 1.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke	Drug: Desmoteplase; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 270 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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 Start Date: Apr 1, 2009
• Actual Primary Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Desmoteplase	Drug: Desmoteplase; 90 μg/kg bodyweight, IV, single bolus over 1 to 2 minutes on 1st day
Placebo Comparator: Placebo	Drug: Placebo; IV, single bolus over 1 to 2 minutes on 1st day

Outcome Measures

Primary Outcome Measures

1. Modified Rankin Scale Score (mRS) (Percentage of Participants With mRS Scores 0-2) [Day 90]

   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

Secondary Outcome Measures

1. National Institutes of Health Stroke Scale (NIHSS) Score. (Percentage of Participants With NIHSS Scores <=1 or NIHSS Decrease >=8) [90 days]

   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.

2. Composite of mRS & NIHSS Response (Percentage of Participants With mRS Scores 0-2 and (NIHSS <= 1 or NIHSS Decrease >= 8) [Day 90]

   Please see outcomes measure one and two for detailed description of the scales

3. Modified Ranking Scale Score (Using the Ordinal Scale) [Day 90]

   Please see outcomes measure one for detailed description of the mRS scale

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	US053	Phoenix	Arizona	United States	85054
2	US081	Castro Valley	California	United States	94546
3	US089	La Jolla	California	United States	92037
4	US043	Loma Linda	California	United States	92354
5	US008	Los Angeles	California	United States	90024-1777
6	US020	Palo Alto	California	United States	94304
7	US050	Pasadena	California	United States	91105
8	US098	Santa Barbara	California	United States	93105
9	US051	Thousand Oaks	California	United States	91360
10	US068	Englewood	Colorado	United States	80113
11	US063	Fairfield	Connecticut	United States	06824
12	US104	New Haven	Connecticut	United States	06510
13	US049	Pensacola	Florida	United States	32504
14	US109	Atlanta	Georgia	United States	30303
15	US042	Augusta	Georgia	United States	30912
16	US052	Columbus	Georgia	United States	31902
17	US080	Decatur	Georgia	United States	30033
18	US040	Lawrenceville	Georgia	United States	30045
19	US067	Macon	Georgia	United States	31201
20	US085	Savannah	Georgia	United States	31405
21	US086	Savannah	Georgia	United States	31419
22	US093	Chicago	Illinois	United States	60611
23	US101	Chicago	Illinois	United States	60612
24	US044	Chicago	Illinois	United States	60622
25	US074	Evanston	Illinois	United States	60201
26	US073	Glenview	Illinois	United States	60026
27	US091	Maywood	Illinois	United States	60153
28	US088	Oak Lawn	Illinois	United States	60453
29	US016	Indianapolis	Indiana	United States	46260
30	US072	Des Moines	Iowa	United States	50314-2611
31	US061	New Orleans	Louisiana	United States	70112
32	US108	New Orleans	Louisiana	United States	70121
33	US064	Shreveport	Louisiana	United States	71130-3932
34	US014	Baltimore	Maryland	United States	21231
35	US039	Boston	Massachusetts	United States	02114
36	US003	Boston	Massachusetts	United States	02118
37	US017	Worcester	Massachusetts	United States	01605
38	US066	Detroit	Michigan	United States	48201
39	US096	Detroit	Michigan	United States	48202
40	US083	Detroit	Michigan	United States	48236
41	US060	Grand Blanc	Michigan	United States	48439
42	US078	Grand Rapids	Michigan	United States	49503
43	US103	Kalamazoo	Michigan	United States	49007
44	US056	Petoskey	Michigan	United States	49770
45	US113	Royal Oak	Michigan	United States	48073
46	US076	Southfield	Michigan	United States	48075
47	US082	Southfield	Michigan	United States	48075
48	US079	Troy	Michigan	United States	48085
49	US059	Gulfport	Mississippi	United States	39502
50	US048	Springfield	Missouri	United States	65807
51	US077	Lebanon	New Hampshire	United States	03756
52	US055	Edison	New Jersey	United States	08818
53	US115	Neptune	New Jersey	United States	07753
54	US100	Ridgewood	New Jersey	United States	07450
55	US075	Albany	New York	United States	12208
56	US102	Brooklyn	New York	United States	11220
57	US012	Buffalo	New York	United States	14203
58	US026	Stony Brook	New York	United States	11794-8121
59	US037	Greensboro	North Carolina	United States	27401
60	US069	Winston-Salem	North Carolina	United States	27157
61	US038	Cleveland	Ohio	United States	44109
62	US001	Columbus	Ohio	United States	43210
63	US062	Columbus	Ohio	United States	43214
64	US046	Toledo	Ohio	United States	43614
65	US095	Springfield	Oregon	United States	97477
66	US070	Allentown	Pennsylvania	United States	18103
67	US023	Philadelphia	Pennsylvania	United States	19141
68	US099	Pittsburg	Pennsylvania	United States	15212
69	US084	Pittsburg	Pennsylvania	United States	15213
70	US092	Providence	Rhode Island	United States	02903
71	US087	Warwick	Rhode Island	United States	02886
72	US057	Columbia	South Carolina	United States	29203
73	US019	Chattanooga	Tennessee	United States	37403
74	US058	Nashville	Tennessee	United States	37205
75	US021	Houston	Texas	United States	77030
76	US031	Houston	Texas	United States	77030
77	US112	Houston	Texas	United States	77030
78	US047	Richmond	Virginia	United States	23298
79	US006	Winchester	Virginia	United States	22601
80	US011	Madison	Wisconsin	United States	53792
81	US097	Milwaukee	Wisconsin	United States	53226
82	BE008	Brugge		Belgium	8000
83	BE004	Hasselt		Belgium	3500
84	BE005	Roeselare		Belgium	8800
85	BE006	Wilrijk		Belgium	2610
86	BR012	Campinas		Brazil	13083-970
87	BR004	Porto Alegre		Brazil	90020-090
88	BR008	Porto Alegre		Brazil	90035-003
89	BR007	Porto Alegre		Brazil	90110-270
90	BR009	Rio de Janeiro		Brazil	20941-150
91	BR011	Rio de Janeiro		Brazil	22280-000
92	BR006	Salvador		Brazil	40140-110
93	CA001	Calgary	Alberta	Canada	T2N 2T9
94	CA004	Edmonton		Canada	T6L 5X8
95	CA006	Halifax		Canada	B3H 3A7
96	CA008	Mississauga		Canada	L5B 1B8
97	CA007	Ottawa		Canada	K1Y 4E9
98	CA012	Toronto		Canada	M4N 3M5
99	CA002	Toronto		Canada	M5T 2S8
100	CA005	Victoria		Canada	V8R 1J8
101	CL002	Santiago		Chile
102	CL003	Santiago		Chile
103	CL004	Santiago		Chile
104	CL006	Santiago		Chile
105	CL005	Valparaiso		Chile
106	DK002	Aalborg		Denmark	9000
107	DK001	Aarhus		Denmark	8000
108	DK004	Copenhagen NV		Denmark	2400
109	DK003	Glostrup		Denmark	2600
110	FI001	Helsinki		Finland	29
111	FI002	Tampere		Finland	33520
112	FI003	Turku		Finland	20520
113	IE001	Dublin		Ireland	8
114	IT010	Ancona		Italy	60020
115	IT008	Brescia		Italy	25123
116	IT003	Firenze		Italy	50019
117	IT004	Imperia		Italy	18100
118	IT002	Milano		Italy	20132
119	IT006	Milano		Italy	20153
120	IT009	Milano		Italy	20162
121	IT012	Modena		Italy	41100
122	IT001	Rome		Italy	161
123	IT005	Rome		Italy	189
124	IT007	Rozzano		Italy	20089
125	IT011	Verona		Italy	37126
126	MX002	D.f.		Mexico	14269
127	MX003	Mexico City		Mexico	14000
128	MX004	Mexico City		Mexico	14050
129	MX005	Monterrey Nuevo Leon		Mexico
130	NO003	Bergen		Norway	2021
131	NO001	Oslo		Norway	0027
132	NO002	Trondheim		Norway	7006
133	ZA003	Cape Town		South Africa	7130
134	ZA002	Cape Town		South Africa	7405
135	ZA001	Cape Town		South Africa	7800
136	SE002	Lund		Sweden	221 85
137	SE001	Malmø		Sweden	205 02
138	GB012	Belfast		United Kingdom	BT12 6BJ
139	GB004	Christchurch		United Kingdom	BH23 2JX
140	GB010	Dundee		United Kingdom	DD1 9SY
141	GB002	Exeter		United Kingdom	EX2 5DW
142	GB009	Glasgow		United Kingdom	G11 6NT
143	GB007	Glasgow		United Kingdom	G51 4TF
144	GB011	Liverpool		United Kingdom	L7 8XP
145	GB006	London		United Kingdom	SE5 8AF
146	GB003	London		United Kingdom	SW17 0RE
147	GB001	Newcastle upon Tyne		United Kingdom	NE1 4LP
148	GB016	Nottingham		United Kingdom	NG5 1PB
149	GB014	Sheffield		United Kingdom	S10 2JF
150	GB005	Stoke on Trent		United Kingdom	ST4 6QG
151	GB015	Westcliff-on-Sea		United Kingdom	SS0 0RY
152	GB013	Wolverhampton		United Kingdom	WV10 0QP

Sponsors and Collaborators

• H. Lundbeck A/S

Investigators

• Study Director: Email contact via H. Lundbeck A/S, [e-mail]

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• EMA EudraCT Results: 2008-005539-14

Publications

None provided.

• Responsible Party: H. Lundbeck A/S
• ClinicalTrials.gov Identifier: NCT00856661
• Other Study ID Numbers: 12649A; 2008-005539-14
• First Posted: Mar 6, 2009
• Last Update Posted: Mar 16, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by H. Lundbeck A/S: Acute ischemic stroke; Angiography; Desmoteplase; Thrombolytic
• Additional relevant MeSH terms: Stroke; Ischemic Stroke; Salivary plasminogen activator alpha 1, Desmodus rotundus

Study Results

Participant Flow

Arm/Group Title	Desmoteplase	Placebo
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	135
Treated	126	131
Randomized Not Treated	9	4
COMPLETED	108	106
NOT COMPLETED	27	29

Baseline Characteristics

Arm/Group Title	Desmoteplase	Placebo	Total
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 Participants	135	135	270
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.1 (11.1)	68.2 (12.5)	68.6 (11.8)
Sex: Female, Male (Count of Participants)
Female	72 53.3%	69 51.1%	141 52.2%
Male	63 46.7%	66 48.9%	129 47.8%
Race/Ethnicity, Customized (participants) [Number]
White	111 82.2%	115 85.2%	226 83.7%
Black or african americal	11 8.1%	9 6.7%	20 7.4%
Asian	7 5.2%	6 4.4%	13 4.8%
Other	6 4.4%	5 3.7%	11 4.1%

Outcome Measures

1. Primary Outcome

Title	Modified Rankin Scale Score (mRS) (Percentage of Participants With mRS Scores 0-2)
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

Outcome Measure Data

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
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
Measure Participants	124	128
Number [Percentage of participants]	41.9 31%	35.9 26.6%

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
Statistical Test of Hypothesis	p-Value	0.2290
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	National Institutes of Health Stroke Scale (NIHSS) Score. (Percentage of Participants With NIHSS Scores <=1 or NIHSS Decrease >=8)
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

Outcome Measure Data

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
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
Measure Participants	124	128
Number [Percentage of participants]	49.2 36.4%	50.8 37.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Desmoteplase, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9401
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95%; 0.59 to 1.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Composite of mRS & NIHSS Response (Percentage of Participants With mRS Scores 0-2 and (NIHSS <= 1 or NIHSS Decrease >= 8)
Description	Please see outcomes measure one and two for detailed description of the scales
Time Frame	Day 90

Outcome Measure Data

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
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
Measure Participants	124	128
Number [Percentage of participants]	32.3 23.9%	28.9 21.4%

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
Statistical Test of Hypothesis	p-Value	0.5076
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 95%; 0.68 to 2.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Modified Ranking Scale Score (Using the Ordinal Scale)
Description	Please see outcomes measure one for detailed description of the mRS scale
Time Frame	Day 90

Outcome Measure Data

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
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
Measure Participants	124	128
Least Squares Mean (Standard Error) [Scores on a scale]	3.02 (0.14)	3.12 (0.15)

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
Statistical Test of Hypothesis	p-Value	0.6146
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	baseline to end of study
Arm/Group Title	Placebo		Desmoteplase
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Desmoteplase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	56/131 (42.7%)		61/126 (48.4%)
Blood and lymphatic system disorders
Anaemia of chronic disease	0/131 (0%)		1/126 (0.8%)
Coagulopathy	1/131 (0.8%)		0/126 (0%)
Deficiency anaemia	0/131 (0%)		2/126 (1.6%)
Iron deficiency anaemia	0/131 (0%)		1/126 (0.8%)
Leukopenia	0/131 (0%)		1/126 (0.8%)
Normochromic normocytic anaemia	1/131 (0.8%)		1/126 (0.8%)
Pernicious anaemia	0/131 (0%)		1/126 (0.8%)
Cardiac disorders
Acute myocardial infarction	1/131 (0.8%)		2/126 (1.6%)
Atrial fibrillation	4/131 (3.1%)		4/126 (3.2%)
Bradycardia	1/131 (0.8%)		2/126 (1.6%)
Cardiac arrest	1/131 (0.8%)		2/126 (1.6%)
Cardiac failure	0/131 (0%)		2/126 (1.6%)
Cardiac failure congestive	2/131 (1.5%)		0/126 (0%)
Cardiac tamponade	0/131 (0%)		1/126 (0.8%)
Cardiomyopathy	0/131 (0%)		1/126 (0.8%)
Left ventricular dysfunction	1/131 (0.8%)		0/126 (0%)
Mitral valve incompetence	1/131 (0.8%)		0/126 (0%)
Sick sinus syndrome	1/131 (0.8%)		0/126 (0%)
Tachycardia	0/131 (0%)		1/126 (0.8%)
Ventricular tachycardia	2/131 (1.5%)		0/126 (0%)
Eye disorders
Pupils unequal	0/131 (0%)		1/126 (0.8%)
Gastrointestinal disorders
Abdominal discomfort	1/131 (0.8%)		0/126 (0%)
Abdominal pain	1/131 (0.8%)		0/126 (0%)
Gastric haemorrhage	1/131 (0.8%)		0/126 (0%)
Gastrointestinal haemorrhage	1/131 (0.8%)		0/126 (0%)
Haematochezia	1/131 (0.8%)		0/126 (0%)
Vomiting	0/131 (0%)		1/126 (0.8%)
General disorders
Catheter site phlebitis	0/131 (0%)		1/126 (0.8%)
Death	0/131 (0%)		1/126 (0.8%)
Multi-organ failure	1/131 (0.8%)		0/126 (0%)
Hepatobiliary disorders
Cholangitis	0/131 (0%)		1/126 (0.8%)
Cholelithiasis	0/131 (0%)		1/126 (0.8%)
Infections and infestations
Bacterial sepsis	1/131 (0.8%)		0/126 (0%)
Bronchopneumonia	1/131 (0.8%)		0/126 (0%)
Endocarditis bacterial	1/131 (0.8%)		1/126 (0.8%)
Gastroenteritis	0/131 (0%)		1/126 (0.8%)
Lower respiratory tract infection	0/131 (0%)		1/126 (0.8%)
Pneumonia	1/131 (0.8%)		3/126 (2.4%)
Pneumonia bacterial	4/131 (3.1%)		5/126 (4%)
Pulmonary sepsis	1/131 (0.8%)		0/126 (0%)
Pyelonephritis acute	0/131 (0%)		1/126 (0.8%)
Sepsis	2/131 (1.5%)		0/126 (0%)
Staphylococcal infection	1/131 (0.8%)		0/126 (0%)
Urinary tract infection	0/131 (0%)		1/126 (0.8%)
Urinary tract infection bacterial	0/131 (0%)		2/126 (1.6%)
Urosepsis	1/131 (0.8%)		0/126 (0%)
Injury, poisoning and procedural complications
Hip fracture	0/131 (0%)		1/126 (0.8%)
Investigations
Blood culture positive	0/131 (0%)		1/126 (0.8%)
Electrocardiogram abnormal	0/131 (0%)		1/126 (0.8%)
Haemoglobin decreased	4/131 (3.1%)		2/126 (1.6%)
Nih stroke scale score increased	4/131 (3.1%)		0/126 (0%)
Oxygen saturation decreased	0/131 (0%)		1/126 (0.8%)
Platelet count decreased	0/131 (0%)		1/126 (0.8%)
Respiratory rate increased	0/131 (0%)		1/126 (0.8%)
Metabolism and nutrition disorders
Dehydration	1/131 (0.8%)		0/126 (0%)
Hypoglycaemia	0/131 (0%)		1/126 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cardiac valve fibroelastoma	1/131 (0.8%)		0/126 (0%)
Colorectal cancer	0/131 (0%)		1/126 (0.8%)
Hepatocellular carcinoma	1/131 (0.8%)		0/126 (0%)
Lung adenocarcinoma	0/131 (0%)		1/126 (0.8%)
Metastases to central nervous system	1/131 (0.8%)		0/126 (0%)
Nervous system disorders
Basal ganglia haemorrhage	0/131 (0%)		1/126 (0.8%)
Brain oedema	6/131 (4.6%)		3/126 (2.4%)
Brain stem stroke	0/131 (0%)		1/126 (0.8%)
Carotid artery stenosis	0/131 (0%)		1/126 (0.8%)
Cerebral artery occlusion	0/131 (0%)		1/126 (0.8%)
Cerebral haemorrhage	1/131 (0.8%)		2/126 (1.6%)
Cerebrovascular accident	1/131 (0.8%)		0/126 (0%)
Depressed level of consciousness	0/131 (0%)		1/126 (0.8%)
Embolic stroke	1/131 (0.8%)		0/126 (0%)
Grand mal convulsion	1/131 (0.8%)		0/126 (0%)
Haemorrhage intracranial	2/131 (1.5%)		2/126 (1.6%)
Haemorrhagic transformation stroke	0/131 (0%)		4/126 (3.2%)
Intracranial pressure increased	0/131 (0%)		1/126 (0.8%)
Ischaemic cerebral infarction	0/131 (0%)		1/126 (0.8%)
Ischaemic stroke	5/131 (3.8%)		3/126 (2.4%)
Loss of consciousness	0/131 (0%)		1/126 (0.8%)
Neurological decompensation	2/131 (1.5%)		0/126 (0%)
Stroke in evolution	6/131 (4.6%)		10/126 (7.9%)
Syncope	1/131 (0.8%)		0/126 (0%)
Transient ischaemic attack	0/131 (0%)		3/126 (2.4%)
Psychiatric disorders
Agitation	1/131 (0.8%)		0/126 (0%)
Major depression	0/131 (0%)		2/126 (1.6%)
Suicidal ideation	0/131 (0%)		1/126 (0.8%)
Renal and urinary disorders
Renal failure acute	2/131 (1.5%)		1/126 (0.8%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	2/131 (1.5%)		0/126 (0%)
Aspiration	0/131 (0%)		1/126 (0.8%)
Pneumonia aspiration	1/131 (0.8%)		0/126 (0%)
Pneumothorax	0/131 (0%)		1/126 (0.8%)
Pulmonary embolism	3/131 (2.3%)		1/126 (0.8%)
Pulmonary oedema	1/131 (0.8%)		1/126 (0.8%)
Respiratory acidosis	0/131 (0%)		1/126 (0.8%)
Respiratory distress	1/131 (0.8%)		1/126 (0.8%)
Respiratory failure	0/131 (0%)		3/126 (2.4%)
Vascular disorders
Deep vein thrombosis	1/131 (0.8%)		1/126 (0.8%)
Hypotension	0/131 (0%)		1/126 (0.8%)
Other (Not Including Serious) Adverse Events
	Placebo		Desmoteplase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	107/131 (81.7%)		98/126 (77.8%)
Cardiac disorders
Atrial fibrillation	13/131 (9.9%)		11/126 (8.7%)
Gastrointestinal disorders
Constipation	32/131 (24.4%)		30/126 (23.8%)
Diarrhoea	8/131 (6.1%)		6/126 (4.8%)
Nausea	14/131 (10.7%)		12/126 (9.5%)
Vomiting	13/131 (9.9%)		7/126 (5.6%)
General disorders
Oedema peripheral	1/131 (0.8%)		11/126 (8.7%)
Pain	7/131 (5.3%)		7/126 (5.6%)
Pyrexia	11/131 (8.4%)		8/126 (6.3%)
Infections and infestations
Pneumonia bacterial	7/131 (5.3%)		3/126 (2.4%)
Urinary tract infection	4/131 (3.1%)		8/126 (6.3%)
Urinary tract infection bacterial	26/131 (19.8%)		22/126 (17.5%)
Injury, poisoning and procedural complications
Fall	9/131 (6.9%)		3/126 (2.4%)
Investigations
Blood potassium decreased	4/131 (3.1%)		8/126 (6.3%)
Nih stroke scale score increased	10/131 (7.6%)		8/126 (6.3%)
Metabolism and nutrition disorders
Hypercholesterolaemia	12/131 (9.2%)		9/126 (7.1%)
Hyperglycaemia	1/131 (0.8%)		7/126 (5.6%)
Hypokalaemia	20/131 (15.3%)		18/126 (14.3%)
Musculoskeletal and connective tissue disorders
Pain in extremity	7/131 (5.3%)		9/126 (7.1%)
Nervous system disorders
Headache	22/131 (16.8%)		22/126 (17.5%)
Stroke in evolution	7/131 (5.3%)		7/126 (5.6%)
Psychiatric disorders
Anxiety	8/131 (6.1%)		11/126 (8.7%)
Depressive symptom	13/131 (9.9%)		13/126 (10.3%)
Insomnia	11/131 (8.4%)		15/126 (11.9%)
Renal and urinary disorders
Haematuria	7/131 (5.3%)		6/126 (4.8%)
Urinary retention	8/131 (6.1%)		3/126 (2.4%)
Vascular disorders
Hypertension	14/131 (10.7%)		16/126 (12.7%)
Hypotension	7/131 (5.3%)		4/126 (3.2%)

Limitations/Caveats

[Not Specified]

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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.