ALIAS: Albumin in Acute Ischemic Stroke Trial

• Sponsor: University of Miami (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00235495
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS) (NIH), University of Calgary (Other), Medical University of South Carolina (Other), Neurological Emergencies Treatment Trials Network (NETT) (Other)
• Enrollment: 841
• Locations: 89
• Arms: 2
• Duration (Months): 80.1
• Patients Per Site: 9.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The goal of the trial is to determine whether human albumin, administered within 5 hours of symptom onset, improves the 3-month outcome of subjects with acute ischemic stroke.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke	Biological: Albumin; Drug: Saline	Phase 3

Detailed Description

Human serum albumin, at 2 g/kg, administered over 2 hours by intravenous infusion, will be compared to placebo (isovolumic normal saline) among patients with acute ischemic stroke. All patients will have a baseline stroke severity measured as NIH Stroke scale score > 5. Patients will treated according to the best standard of care including concurrent treatment with intravenous or intra-arterial thrombolysis where appropriate. The primary outcome will be determined at 3 months. The primary hypothesis is that, using the composite outcome of a modified Rankin score 0-1 or NIH stroke scale score 0-1 at 3 months (or both), the proportion of patients with improved outcomes will be greater by 10% or more in the active treatment group. [The current trial is termed "Part 2" and incorporates revisions to the initial protocol that were instituted after the Data Safety Monitoring Board (DSMB) suspended subject recruitment because of a safety concern after 434 subjects had been enrolled. The protocol revisions of Part 2 resulted from the study team's thorough review of the Part-1 safety data and were designed to optimize safety going forward.]

Study Design

• Study Type: Interventional
• Actual Enrollment: 841 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III Randomized Multicenter Clinical Trial Of High-Dose Human Albumin Therapy For Neuroprotection In Acute Ischemic Stroke
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Albumin (ALB) Albumin (human albumin, 25% solution, 2.0 g/kg), infused intravenously over a period of 2 hours	Biological: Albumin; human albumin, 25%, 2.0g/kg intravenously (or equivalent volume of saline control), infused over 2 h, commencing within 5 hours of stroke onset
Placebo Comparator: Saline Saline (isotonic solution), 8 ml/kg, infused intravenously over a 2-hour period	Drug: Saline; equivalent volume of isotonic saline control

Outcome Measures

Primary Outcome Measures

1. The Number of Participants With Favorable Outcome Defined as National Institute of Health Stroke Scale (NIHSS) Score of 0-1 and/or Modified Rankin Scale (mRS) of 0-1. [at 3 months]

   The National Institutes of Health Stroke Scale (NIHSS) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. The scores range from 0 to 42 with a score of greater than 20 indicating severe neurologic deficit. The mRS ranges from 0-6 representing perfect health without symptoms to death. A score of 0 is no symptoms at all and a score of 1 is no significant disability. Able to carry out all usual duties and activities.

Secondary Outcome Measures

1. Number of Participants With a Composite Outcome of mRS 0-1 and/or NIHSS 0-1 and/or Decrease in NIHSS From Baseline by 10 or More Points [at 3 months]

2. Number of Participants With a NIHSS of 0-1 at 24 Hours [at 24 hours]

   The National Institutes of Health Stroke Scale (NIHSS) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. The scores range from 0 to 42 with a score of greater than 20 indicating severe neurologic deficit.

3. Number of Participants With a NIHSS 0-1 at 90 Days. [at 90 days]

   The National Institutes of Health Stroke Scale (NIHSS) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. The scores range from 0 to 42 with a score of greater than 20 indicating severe neurologic deficit.

4. The Number of Participants With a Score on the mRS 0-1 at 90 Days. [at 90 days]

   The mRS ranges from 0-6 representing perfect health without symptoms to death. 0 = No symptoms at all. 1 = No significant disability. Able to carry out all usual duties and activities. 2 = Slight disability. Unable to carry out all previous activities but able to look after own affairs without assistance. 3 = Moderate disability. Requires some help, but able to walk unassisted. 4 = Moderately severe disability. Unable to walk unassisted and unable to attend to own bodily needs without assistance. 5 = Severe disability. Bedridden, incontinent, and requires constant nursing care and attention. 6 = Dead.

5. The Number of Participants With a Score on the mRS of 0-2 at 90 Days. [at 90 days]

   The mRS ranges from 0-6 representing perfect health without symptoms to death. 0 = No symptoms at all. 1 = No significant disability. Able to carry out all usual duties and activities. 2 = Slight disability. Unable to carry out all previous activities but able to look after own affairs without assistance. 3 = Moderate disability. Requires some help, but able to walk unassisted. 4 = Moderately severe disability. Unable to walk unassisted and unable to attend to own bodily needs without assistance. 5 = Severe disability. Bedridden, incontinent, and requires constant nursing care and attention. 6 = Dead.

6. Number of Participants With a Favorable Outcome Per Modified Rankin Scare (mRS) [90 days]

   Assessed as the final global disability level on the modified Rankin scale (mRS) at 90 days better than expectation (sliding dichotomy analysis) ) assessed in the intention to treat population. mRS Scale: 0 - No symptoms. - No significant disability. Able to carry out all usual activities, despite some symptoms. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. - Moderate disability. Requires some help, but able to walk unassisted. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. - Dead.

7. Barthel Index (BI) 95-100 [at 90 days]

   The Barthel Index (BI) is an ordinal scale used to measure a subject's performance in activities of daily living (ADL) in ten variables - feeding, transfer (bed to chair), grooming, toilet use, bathing, mobility on a level surface, stair use, dressing, bowels and bladder. It is an assessment of independence in ADL and is scored in increments of 5 points. the highest total score for fully independent subjects equals 100. A higher number is associated with a greater likelihood of being able to live at home with a degree of independence.

8. Number of Participants With an EuroQol (EQ-5D) Favorable Score < 0.78 [at 90 days]

   The EQ-5D measures the subject's overall health state in a descriptive system of health-related quality of life (QoL) states consisting of five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which can take one of three responses. The responses record three levels of severity ('no problems', 'some problems', and 'extreme problems) within a particular EQ-5D dimension. The EQ-5D results can be converted to health utility scores.

9. Number of Participants With a Stroke Specific Quality of Life Scale (SSQOL) Score of >=3 [at 90 days]

   Stroke, specific, health-related quality of life (SSQoL) is a self-reported survey that includes 12 domains and 49 items which are scored on a 5pt Likert response format with a lower score indicating worse function/lower ability on that item or domain. Domain scores were calculated as an unweighted average of item scores in that domain. Overall Total Score was calculated as an unweighted average of domain scores. Each Domain Score and the Overall Total Score all range from 1-5 with 1 being worst and 5 being the best. We have presented data here for the number of participants that have an unweighted average of domain scores of 3 or greater.

10. Trailmaking A [at 90 days]

    The Trail Making Test is a neuropsychological test of visual attention and task switching that is thought to be sensitive to the presence of cerebral dysfunction. It is a timed test consisting of two parts where the subject is asked to draw a "trail" made by connecting numbers in sequential order (part A) and then in part B the combination of numbers and letters. Scoring is calculated separately for Parts A and B but both scores are provided as the minutes and seconds it takes for the subject to complete ach part. Normally, the entire test (A and B) can be completed in 5-10 minutes.

11. Trailmaking B [at 90 days]

    The Trail Making Test is a neuropsychological test of visual attention and task switching that is thought to be sensitive to the presence of cerebral dysfunction. It is a timed test consisting of two parts where the subject is asked to draw a "trail" made by connecting numbers in sequential order (part A) and then in part B the combination of numbers and letters. Scoring is calculated separately for Parts A and B but both scores are provided as the minutes and seconds it takes for the subject to complete ach part. Normally, the entire test (A and B) can be completed in 5-10 minutes.

12. Number of Participants With Neurological Deterioration Within 48 Hours [within 48 hours]

    This is assessed as the number of participants with a neurological adverse event.

13. Neurological Death Within 7 Days [within 7 days]

14. Recurrent Ischemic Stroke Within 30 Days [within 30 days]

15. Atrial Fibrillation Within 48 Hours [within 48 hours]

16. Pulmonary Edema Within 48 Hours [within 48 hours]

17. Shortness of Breath Within 48 Hours [within 48 hours]

18. Symptomatic Intracerebral Hemorrhage (ICH) Within 24 Hours [within 24 hours]

19. Asymptomatic ICH Within 24 Hours [within 24 hours]

20. Death Within 30 Days [within 30 days]

21. Death Within 90 Days [within 90 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 83 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Acute ischemic stroke

• NIH stroke scale score > 5

• Age >= 18 and <= 83

• ALB or placebo can be administered within 5 hours of symptom onset

• ALB or placebo can be administered within 60 minutes of Tissue Plasminogen Activator (tPA) administration in the thrombolysis group

• Signed informed consent

Exclusion Criteria:

• Episode/exacerbation of congestive heart failure (CHF) from any cause in the last 6 months. An episode of congestive heart failure is any heart failure that required a change in medication, diet or hospitalization.

• Known valvular heart disease with CHF in the last 6 months.

• Severe aortic stenosis or mitral stenosis.

• Cardiac surgery involving thoracotomy (e.g., coronary artery bypass graft (CABG), valve replacement surgery) in the last 6 months.

• Acute myocardial infarction in the last 6 months.

• Signs or symptoms of acute myocardial infarction, including ECG findings, on admission.

• Baseline elevated serum troponin level on admission (>0.1 mcg/L)

• Suspicion of aortic dissection on admission.

• Acute arrhythmia (including any tachycardia - or bradycardia) with hemodynamic instability.

• Findings on physical examination of any of the following: (1) jugular venous distention (JVP > 4 cm above the sternal angle); (2) 3rd heart sound; (3) resting tachycardia (heart rate > 100/min) attributable to congestive heart failure; (4) abnormal hepatojugular reflux; (5) lower extremity pitting edema attributable to congestive heart failure; and/or (6) definite chest x-ray evidence of pulmonary edema.

• Current acute or chronic lung disease requiring supplemental chronic or intermittent oxygen therapy.

• Historical Modified Rankin Score (mRS) ≥2. Patients who live in a nursing home or who are not fully independent for activities of daily living immediately prior to the stroke are not eligible for the trial.

• In-patient stroke. I.e., patients with a stroke occurring as a complication of hospitalization for another condition, or as a complication of a procedure.

• Planned acute use of intra-arterial (IA) tPA or acute endovascular intervention (e.g., stenting, angioplasty, thrombus retrieval device use) must conform to the following criteria: (1) begin within 5 hours of symptom onset, and (2) finish within 7 hours of symptom-onset.

• Fever, defined as core body temperature > 37.5° C (99.5°F).

• Serum creatinine > 2.0 mg/dL or 180 µmol/L.

• Profound dehydration.

• Evidence of intracranial hemorrhage (intracerebral hematoma (ICH), subarachnoid hemorrhage (SAH), epidural hemorrhage, acute or chronic subdural hematoma (SDH)) on the baseline CT or MRI scan.

• History of allergy to albumin.

• History of latex rubber allergy.

• Severe chronic anemia with Hgb < 7.5 g/dL

• Pregnancy, breastfeeding or positive pregnancy test. (Women of childbearing age must have a negative pregnancy test prior to ALB administration.)

• Concurrent participation in any other therapeutic clinical trial.

• Evidence of any other major life-threatening or serious medical condition that would prevent completion of 3-month follow-up, impair the assessment of outcome, or in which ALB therapy would be contraindicated or might cause harm to the subject.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
2	University of Arizona Medical Center-South Campus	Tucson	Arizona	United States	85724-5030
3	University of Arizona Medical Center	Tucson	Arizona	United States	85724
4	John Muir Medical Ctr-Concord	Concord	California	United States	94520
5	El Camino Hospital	Mountain View	California	United States	94040-4378
6	UCSF Medical Center	San Francisco	California	United States	94110
7	UCSF-San Francisco General Hospital	San Francisco	California	United States	94110
8	California Pacific Medical Center, Davies Campus	San Francisco	California	United States	94114
9	California Pacific Medical Center, Pacific Campus	San Francisco	California	United States	94115
10	O'Connor Hospital	San Jose	California	United States	95128
11	UCLA Medical Center, Santa Monica	Santa Monica	California	United States	90024
12	Stanford University Medical Center	Stanford	California	United States	94305
13	John Muir Medical Ctr-Walnut Creek	Walnut Creek	California	United States	94598
14	Yale University School of Medicine	New Haven	Connecticut	United States	06510
15	Christiana Hospital	Newark	Delaware	United States	19718
16	University of Florida/Shands	Jacksonville	Florida	United States	32209
17	Jackson Memorial Hospital, University of Miami	Miami	Florida	United States	33136-1096
18	The Villages Research Group	Ocala	Florida	United States	34474
19	Neuroscience Research Institute at Florida Hospital Orlando	Orlando	Florida	United States	32804
20	Intercoastal Neurology/Medical Research Center	Sarasota	Florida	United States	34239
21	Grady Memorial Hospital	Atlanta	Georgia	United States	30303
22	Emory University Hospital	Atlanta	Georgia	United States	30322
23	Loyola University Medical Center	Maywood	Illinois	United States	60153
24	St. Elizabeth Medical Center South	Edgewood	Kentucky	United States	41017
25	St. Elizabeth Hospital	Florence	Kentucky	United States	41042
26	University of Kentucky Hospital	Lexington	Kentucky	United States	40536
27	University of Maryland Medical Center	Baltimore	Maryland	United States	21201-1595
28	Upper Chesapeake Medical Center	Bel Air	Maryland	United States	21014
29	Detroit Receiving Hospital	Detroit	Michigan	United States	48201
30	Henry Ford Hospital	Detroit	Michigan	United States	48202
31	Sinai-Grace Hospital	Detroit	Michigan	United States	48235
32	William Beaumont Hospital	Royal Oak	Michigan	United States	48073
33	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
34	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
35	University of Minnesota Medical Center Fairview	Minneapolis	Minnesota	United States	55454
36	HealthEast Care System/St. Joseph's Hospital	Saint Paul	Minnesota	United States	55102
37	Saint Louis University	Saint Louis	Missouri	United States	63110
38	Atlantic Neuroscience Institute, Overlook Hospital	Summit	New Jersey	United States	07902
39	New York Methodist Hospital	Brooklyn	New York	United States	11215
40	Buffalo General Medical Center	Buffalo	New York	United States	14203
41	Mercy Hospital of Buffalo	Buffalo	New York	United States	14220
42	Winthrop University Hospital	Mineola	New York	United States	11501
43	Columbia University Medical Center	New York	New York	United States	10032
44	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599-7025
45	Duke University Medical Center	Durham	North Carolina	United States	27710
46	Wake Med Health and Hospitals	Raleigh	North Carolina	United States	27610
47	Christ Hospital	Cincinnati	Ohio	United States	45219
48	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45219
49	Good Samaritan Hospital	Cincinnati	Ohio	United States	45220
50	Bethesda North Hospital	Cincinnati	Ohio	United States	45242-4402
51	MetroHealth Medical Center	Cleveland	Ohio	United States	44109-1998
52	Ohio State University Medical Center	Columbus	Ohio	United States	43210
53	Mercy Health Fairfield Hospital	Fairfield	Ohio	United States	45014
54	Providence Portland Medical Center	Portland	Oregon	United States	97213
55	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
56	OHSU Legacy Emmanuel Hospital	Portland	Oregon	United States	97227
57	Oregon Health & Science University	Portland	Oregon	United States	97239-3098
58	Sacred Heart Medical Center	Springfield	Oregon	United States	97477
59	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
60	Penn State Hershey Medical Center	Hershey	Pennsylvania	United States	17033
61	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania	United States	19104
62	Temple University Hospital	Philadelphia	Pennsylvania	United States	19130
63	Hahnemann University Hospital	Philadelphia	Pennsylvania	United States	19140
64	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
65	Seton Medical Center	Austin	Texas	United States	78701
66	Baylor College of Medicine	Houston	Texas	United States	77030
67	Memorial Hermann Texas Medical Center	Houston	Texas	United States	77030
68	Virginia Commonwealth University Medical Center	Richmond	Virginia	United States	23219
69	Froedtert Memorial Hospital	Milwaukee	Wisconsin	United States	53226
70	Foothills Hospital, University of Calgary	Calgary	Alberta	Canada	T2N 2T9
71	University of Alberta	Edmonton	Alberta	Canada	T6G 1Z1
72	Grey Nuns Community Hospital	Edmonton	Alberta	Canada	T6L 5X8
73	Royal Island Hospital	Kamloops	British Columbia	Canada	V2C 2T1
74	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z 1M9
75	Queen Elizabeth II Health Science Centre	Halifax	Nova Scotia	Canada	B3H-3A7
76	London Health Sciences Centre-University Hospital	London	Ontario	Canada	N6A 5A5
77	Trillium Health Centre	Mississauga	Ontario	Canada	L5B 1B8
78	The Ottawa Hospital	Ottawa	Ontario	Canada	K1Y 4E9
79	Thunder Bay Regional Health Sciences Centre	Thunder Bay	Ontario	Canada	P7B 7C7
80	University of Toronto, St. Michael's Hospital	Toronto	Ontario	Canada	M5C 1R6
81	Hopital Charles LeMoyne, Centre de Recherche	Greenfield Park	Quebec	Canada	J4V 2H1
82	Centre de Sante et de Service Sociaux de Chicoutimi	Saguenay	Quebec	Canada	G7H 5H6
83	Helsinki University Central Hospital	Helsinki		Finland	FI-00290
84	Tampere University Hospital	Tampere		Finland	FI-33521
85	Hadassah Medical Organization, Hadassah University Hospital	Ein Kerem	Jerusalem	Israel
86	Chaim Sheba Medical Center at Tel-Hashomer	Tel Hashomer	Ramat Gan	Israel	52621
87	Soroka Medical Center	Beer Sheva		Israel	84101
88	Rambam Health Care Campus	Haifa		Israel	31096
89	Tel-Aviv Sourasky Medical Center	Tel Aviv		Israel	64239

Sponsors and Collaborators

• University of Miami
• National Institute of Neurological Disorders and Stroke (NINDS)
• University of Calgary
• Medical University of South Carolina
• Neurological Emergencies Treatment Trials Network (NETT)

Investigators

• Study Chair: Myron D. Ginsberg, MD, University of Miami
• Principal Investigator: Michael D. Hill, MD MSc, University of Calgary
• Principal Investigator: Yuko Y Palesch, PhD, Medical University of South Carolina

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Myron Ginsberg, Principal Investigator; Peritz Scheinberg Professor of Neurology, University of Miami
• ClinicalTrials.gov Identifier: NCT00235495
• Other Study ID Numbers: 20060083; U01NS054630; NIH NINDS 5U01 NS040406-08; 20060233
• First Posted: Oct 10, 2005
• Last Update Posted: Dec 17, 2019
• Last Verified: Dec 1, 2019

• Keywords provided by Myron Ginsberg, Principal Investigator; Peritz Scheinberg Professor of Neurology, University of Miami: stroke
• Additional relevant MeSH terms: Stroke; Ischemic Stroke; Cerebral Infarction; Ischemia

Study Results

Participant Flow

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Period Title: Overall Study
STARTED	422	419
COMPLETED	354	351
NOT COMPLETED	68	68

Baseline Characteristics

Arm/Group Title	Albumin	Saline	Total
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline	Total of all reporting groups
Overall Participants	422	419	841
Age (Count of Participants)
<=18 years	1 0.2%	0 0%	1 0.1%
Between 18 and 65 years	202 47.9%	188 44.9%	390 46.4%
>=65 years	219 51.9%	231 55.1%	450 53.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.42 (12.95)	64.84 (12.88)	64.13 (12.93)
Sex: Female, Male (Count of Participants)
Female	202 47.9%	184 43.9%	386 45.9%
Male	220 52.1%	235 56.1%	455 54.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	24 5.7%	26 6.2%	50 5.9%
Not Hispanic or Latino	379 89.8%	372 88.8%	751 89.3%
Unknown or Not Reported	19 4.5%	21 5%	40 4.8%
Race/Ethnicity, Customized (Count of Participants)
American Indian/Alaska Native/First Nations People	2 0.5%	0 0%	2 0.2%
Asian	25 5.9%	20 4.8%	45 5.4%
Native Hawaiian or Other Pacific Islander	2 0.5%	1 0.2%	3 0.4%
Black	69 16.4%	86 20.5%	155 18.4%
White	314 74.4%	305 72.8%	619 73.6%
Multiple, Other, or Unknown	10 2.4%	7 1.7%	17 2%
Oxfordshire Community Stroke Project Classification (Count of Participants)
Total Anterior Circulation Syndrome	102 24.2%	98 23.4%	200 23.8%
Partial Anterior Circulation Syndrome	232 55%	235 56.1%	467 55.5%
Posterior Circulation Syndrome	35 8.3%	39 9.3%	74 8.8%
Lacunar Stroke	53 12.6%	47 11.2%	100 11.9%
Baseline National Institutes of Health Stroke Scale (NIHSS) Score (units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [units on a scale]	11	11	11
Baseline ASPECTS (Number) [Number]
Baseline ASPECTS >7	325 77%	327 78%	652 77.5%
Baseline ASPECTS <= 7	93 22%	88 21%	181 21.5%
Missing	4 0.9%	4 1%	8 1%

Outcome Measures

1. Primary Outcome

Title	The Number of Participants With Favorable Outcome Defined as National Institute of Health Stroke Scale (NIHSS) Score of 0-1 and/or Modified Rankin Scale (mRS) of 0-1.
Description	The National Institutes of Health Stroke Scale (NIHSS) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. The scores range from 0 to 42 with a score of greater than 20 indicating severe neurologic deficit. The mRS ranges from 0-6 representing perfect health without symptoms to death. A score of 0 is no symptoms at all and a score of 1 is no significant disability. Able to carry out all usual duties and activities.
Time Frame	at 3 months

Outcome Measure Data

Analysis Population Description

Intent to Treat population - All subjects randomized into the study are included and analyzed based on the treatment arm to which they were randomized.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	422	419
Count of Participants [Participants]	186 44.1%	185 44.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments	Test of null hypothesis (equal proportions of subjects with NIHSS 0-1 or mRS 0-1 or both at 90 days post-randomization in Albumin and Saline treatment arms) versus alternative hypothesis (greater proportion of subjects with NIHSS 0-1 or mRS 0-1 or both at 90 days post-randomization in Albumin treatment arm).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted risk ratio greater than 1 indicates greater risk of good outcome in the Albumin treatment group, while adjusted risk ratio less than 1 indicates greater risk of good outcome in the Saline treatment group.

2. Secondary Outcome

Title	Number of Participants With a Composite Outcome of mRS 0-1 and/or NIHSS 0-1 and/or Decrease in NIHSS From Baseline by 10 or More Points
Time Frame	at 3 months

Outcome Measure Data

Analysis Population Description

Intent to Treat population - All subjects randomized into the study are included and analyzed based on the treatment arm to which they were randomized.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	422	419
Count of Participants [Participants]	227 53.8%	241 57.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 99%; 0.80 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants With a NIHSS of 0-1 at 24 Hours
Description	The National Institutes of Health Stroke Scale (NIHSS) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. The scores range from 0 to 42 with a score of greater than 20 indicating severe neurologic deficit.
Time Frame	at 24 hours

Outcome Measure Data

Analysis Population Description

Intent to Treat population - All subjects randomized into the study are included and analyzed based on the treatment arm to which they were randomized.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	422	419
Count of Participants [Participants]	65 15.4%	62 14.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 99%; 0.66 to 1.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Participants With a NIHSS 0-1 at 90 Days.
Description	The National Institutes of Health Stroke Scale (NIHSS) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. The scores range from 0 to 42 with a score of greater than 20 indicating severe neurologic deficit.
Time Frame	at 90 days

Outcome Measure Data

Analysis Population Description

Intent to Treat population - All subjects randomized into the study are included and analyzed based on the treatment arm to which they were randomized.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	422	419
Count of Participants [Participants]	65 15.4%	62 14.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 99%; 0.71 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	The Number of Participants With a Score on the mRS 0-1 at 90 Days.
Description	The mRS ranges from 0-6 representing perfect health without symptoms to death. 0 = No symptoms at all. 1 = No significant disability. Able to carry out all usual duties and activities. 2 = Slight disability. Unable to carry out all previous activities but able to look after own affairs without assistance. 3 = Moderate disability. Requires some help, but able to walk unassisted. 4 = Moderately severe disability. Unable to walk unassisted and unable to attend to own bodily needs without assistance. 5 = Severe disability. Bedridden, incontinent, and requires constant nursing care and attention. 6 = Dead.
Time Frame	at 90 days

Outcome Measure Data

Analysis Population Description

Intent to Treat population - All subjects randomized into the study are included and analyzed based on the treatment arm to which they were randomized.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	422	419
Count of Participants [Participants]	155 36.7%	145 34.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 99%; 0.82 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	The Number of Participants With a Score on the mRS of 0-2 at 90 Days.
Description	The mRS ranges from 0-6 representing perfect health without symptoms to death. 0 = No symptoms at all. 1 = No significant disability. Able to carry out all usual duties and activities. 2 = Slight disability. Unable to carry out all previous activities but able to look after own affairs without assistance. 3 = Moderate disability. Requires some help, but able to walk unassisted. 4 = Moderately severe disability. Unable to walk unassisted and unable to attend to own bodily needs without assistance. 5 = Severe disability. Bedridden, incontinent, and requires constant nursing care and attention. 6 = Dead.
Time Frame	at 90 days

Outcome Measure Data

Analysis Population Description

Intent to Treat population - All subjects randomized into the study are included and analyzed based on the treatment arm to which they were randomized.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	422	419
Count of Participants [Participants]	227 53.8%	221 52.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 99%; 0.85 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number of Participants With a Favorable Outcome Per Modified Rankin Scare (mRS)
Description	Assessed as the final global disability level on the modified Rankin scale (mRS) at 90 days better than expectation (sliding dichotomy analysis) ) assessed in the intention to treat population. mRS Scale: 0 - No symptoms. - No significant disability. Able to carry out all usual activities, despite some symptoms. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. - Moderate disability. Requires some help, but able to walk unassisted. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. - Dead.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

Intent to Treat population - All subjects randomized into the study are included and analyzed based on the treatment arm to which they were randomized.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	422	419
Count of Participants [Participants]	142 33.6%	141 33.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 99%; 0.87 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Barthel Index (BI) 95-100
Description	The Barthel Index (BI) is an ordinal scale used to measure a subject's performance in activities of daily living (ADL) in ten variables - feeding, transfer (bed to chair), grooming, toilet use, bathing, mobility on a level surface, stair use, dressing, bowels and bladder. It is an assessment of independence in ADL and is scored in increments of 5 points. the highest total score for fully independent subjects equals 100. A higher number is associated with a greater likelihood of being able to live at home with a degree of independence.
Time Frame	at 90 days

Outcome Measure Data

Analysis Population Description

Intent to Treat population - All subjects randomized into the study are included and analyzed based on the treatment arm to which they were randomized.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	422	419
BI 95-100	227 53.8%	231 55.1%
Otherwise	195 46.2%	188 44.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 99%; 0.83 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Number of Participants With an EuroQol (EQ-5D) Favorable Score < 0.78
Description	The EQ-5D measures the subject's overall health state in a descriptive system of health-related quality of life (QoL) states consisting of five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which can take one of three responses. The responses record three levels of severity ('no problems', 'some problems', and 'extreme problems) within a particular EQ-5D dimension. The EQ-5D results can be converted to health utility scores.
Time Frame	at 90 days

Outcome Measure Data

Analysis Population Description

Intent to Treat population - All subjects randomized into the study are included and analyzed based on the treatment arm to which they were randomized.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	422	419
Count of Participants [Participants]	155 36.7%	152 36.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 99%; 0.84 to 1.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Number of Participants With a Stroke Specific Quality of Life Scale (SSQOL) Score of >=3
Description	Stroke, specific, health-related quality of life (SSQoL) is a self-reported survey that includes 12 domains and 49 items which are scored on a 5pt Likert response format with a lower score indicating worse function/lower ability on that item or domain. Domain scores were calculated as an unweighted average of item scores in that domain. Overall Total Score was calculated as an unweighted average of domain scores. Each Domain Score and the Overall Total Score all range from 1-5 with 1 being worst and 5 being the best. We have presented data here for the number of participants that have an unweighted average of domain scores of 3 or greater.
Time Frame	at 90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	422	419
Count of Participants [Participants]	258 61.1%	268 64%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 99%; 0.84 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Trailmaking A
Description	The Trail Making Test is a neuropsychological test of visual attention and task switching that is thought to be sensitive to the presence of cerebral dysfunction. It is a timed test consisting of two parts where the subject is asked to draw a "trail" made by connecting numbers in sequential order (part A) and then in part B the combination of numbers and letters. Scoring is calculated separately for Parts A and B but both scores are provided as the minutes and seconds it takes for the subject to complete ach part. Normally, the entire test (A and B) can be completed in 5-10 minutes.
Time Frame	at 90 days

Outcome Measure Data

Analysis Population Description

Participants were excluded if the Tail Making Test was not assessed.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	269	272
Median (Inter-Quartile Range) [Minutes]	55	56

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.913
	Comments
	Method	Wilcoxon rank sum test, normal approx
	Comments
Method of Estimation	Estimation Parameter	Rank Sum
	Estimated Value	73098
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Trailmaking B
Description	The Trail Making Test is a neuropsychological test of visual attention and task switching that is thought to be sensitive to the presence of cerebral dysfunction. It is a timed test consisting of two parts where the subject is asked to draw a "trail" made by connecting numbers in sequential order (part A) and then in part B the combination of numbers and letters. Scoring is calculated separately for Parts A and B but both scores are provided as the minutes and seconds it takes for the subject to complete ach part. Normally, the entire test (A and B) can be completed in 5-10 minutes.
Time Frame	at 90 days

Outcome Measure Data

Analysis Population Description

Intent to Treat population - All subjects randomized into the study are included and analyzed based on the treatment arm to which they were randomized.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	215	210
Median (Inter-Quartile Range) [Minutes]	111	110

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.923
	Comments
	Method	Wilcoxon rank sum test, normal approx
	Comments
Method of Estimation	Estimation Parameter	Rank Sum
	Estimated Value	44853.5
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Number of Participants With Neurological Deterioration Within 48 Hours
Description	This is assessed as the number of participants with a neurological adverse event.
Time Frame	within 48 hours

Outcome Measure Data

Analysis Population Description

The safety sample consisted of the 830 subjects who received at least 20% of the indented dose of study-drug. In order to be considered for this analysis, subject must have had the event within the time frame or been followed for at least 48 hours.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	411	412
Count of Participants [Participants]	47 11.1%	40 9.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Neurological Death Within 7 Days
Time Frame	within 7 days

Outcome Measure Data

Analysis Population Description

The safety sample consisted of the 830 subjects who received at least 20% of the indented dose of study-drug. In order to be considered for this analysis, subject must have had the event within the time frame or been followed for at least 7 days.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	404	407
Number [participants]	13 3.1%	13 3.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.47 to 2.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Recurrent Ischemic Stroke Within 30 Days
Time Frame	within 30 days

Outcome Measure Data

Analysis Population Description

The safety sample consisted of the 830 subjects who received at least 20% of the indented dose of study-drug. In order to be considered for this analysis, subject must have had the event within the time frame or been followed for at least 30 days.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	373	370
Number [participants]	7 1.7%	6 1.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95%; 0.39 to 3.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Atrial Fibrillation Within 48 Hours
Time Frame	within 48 hours

Outcome Measure Data

Analysis Population Description

The safety sample consisted of the 830 subjects who received at least 20% of the indented dose of study-drug. In order to be considered for this analysis, subject must have had the event within the time frame or been followed for at least 48 hours.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	410	412
Number [participants]	32 7.6%	19 4.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.69
	Confidence Interval	(2-Sided) 95%; 0.98 to 2.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Pulmonary Edema Within 48 Hours
Time Frame	within 48 hours

Outcome Measure Data

Analysis Population Description

The safety sample consisted of the 830 subjects who received at least 20% of the indented dose of study-drug. In order to be considered for this analysis, subject must have had the event within the time frame or been followed for at least 48 hours.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	412	412
Number [participants]	54 12.8%	5 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	10.8
	Confidence Interval	(2-Sided) 95%; 4.37 to 26.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	Shortness of Breath Within 48 Hours
Time Frame	within 48 hours

Outcome Measure Data

Analysis Population Description

The safety sample consisted of the 830 subjects who received at least 20% of the indented dose of study-drug. In order to be considered for this analysis, subject must have had the event within the time frame or been followed for at least 48 hours.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	410	412
Number [participants]	18 4.3%	7 1.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	2.58
	Confidence Interval	(2-Sided) 95%; 1.09 to 6.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Symptomatic Intracerebral Hemorrhage (ICH) Within 24 Hours
Time Frame	within 24 hours

Outcome Measure Data

Analysis Population Description

The safety sample consisted of the 830 subjects who received at least 20% of the indented dose of study-drug. In order to be considered for this analysis, subject must have had the event within the time frame or been followed for at least 24 hours.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	415	414
Count of Participants [Participants]	17 4%	7 1.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	2.42
	Confidence Interval	(2-Sided) 95%; 1.02 to 5.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Asymptomatic ICH Within 24 Hours
Time Frame	within 24 hours

Outcome Measure Data

Analysis Population Description

The safety sample consisted of the 830 subjects who received at least 20% of the indented dose of study-drug. In order to be considered for this analysis, subject must have had the event within the time frame or been followed for at least 24 hours.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	415	414
Count of Participants [Participants]	27 6.4%	23 5.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.68 to 2.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Death Within 30 Days
Time Frame	within 30 days

Outcome Measure Data

Analysis Population Description

The safety sample consisted of the 830 subjects who received at least 20% of the indented dose of study-drug. In order to be considered for this analysis, subject must have had the event within the time frame or been followed for at least 30 days.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	409	406
Number [participants]	39 9.2%	37 8.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.68 to 1.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. Secondary Outcome

Title	Death Within 90 Days
Time Frame	within 90 days

Outcome Measure Data

Analysis Population Description

The safety sample consisted of the 830 subjects who received at least 20% of the indented dose of study-drug. In order to be considered for this analysis, subject must have had the event within the time frame or been followed for at least 90 days.

Arm/Group Title	Albumin	Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg	Treatment with same volume of normal saline
Measure Participants	378	369
Number [participants]	46 10.9%	41 9.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Albumin, Saline
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.74 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Albumin		Saline
Arm/Group Description	Treatment with 25% Albumin, 2.0 g/kg		Treatment with same volume of normal saline
All Cause Mortality
	Albumin		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Albumin		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	212/422 (50.2%)		178/419 (42.5%)
Blood and lymphatic system disorders
SYSTEMIC HEMORRHAGE	2/422 (0.5%)	2	1/419 (0.2%)	1
NON-CEREBRAL HEMORRHAGE	1/422 (0.2%)	1	1/419 (0.2%)	1
COAGULOPATHY	1/422 (0.2%)	1	0/419 (0%)	0
ANEMIA	2/422 (0.5%)	2	1/419 (0.2%)	1
THROMBOCYTOPENIA	4/422 (0.9%)	4	0/419 (0%)	0
THROMBOTIC THROMBOCYTOPENIC PURPURA	0/422 (0%)	0	1/419 (0.2%)	1
SYMPTOMATIC INTRACRANIAL HEMORRHAGE	22/422 (5.2%)	22	8/419 (1.9%)	8
ASYMPTOMATIC INTRACRANIAL HEMORRHAGE	2/422 (0.5%)	2	1/419 (0.2%)	1
Cardiac disorders
ANGINA PECTORIS (STABLE)	1/422 (0.2%)	1	1/419 (0.2%)	1
ACUTE CORONARY SYNDROME - MYOCARDIAL INFARCTION	13/422 (3.1%)	15	9/419 (2.1%)	9
CARDIAC ARREST	2/422 (0.5%)	2	6/419 (1.4%)	6
CARDIOGENIC SHOCK	1/422 (0.2%)	1	0/419 (0%)	0
"CONGESTIVE HEART FAILURE, PULMONARY EDEMA"	21/422 (5%)	21	6/419 (1.4%)	7
PERIPHERAL ARTERIAL OCCLUSION	1/422 (0.2%)	1	0/419 (0%)	0
VENTRICULAR FIBRILLATION OR TACHYCARDIA	0/422 (0%)	0	1/419 (0.2%)	1
ATRIAL FIBRILLATION/FLUTTER	10/422 (2.4%)	11	3/419 (0.7%)	3
BRADYCARDIA	3/422 (0.7%)	5	2/419 (0.5%)	2
"CONDUCTION BLOCKS (ATRIO-VENTRICULAR BLOCKS, BUNDLE-BRANCH BLOCKS)"	2/422 (0.5%)	2	0/419 (0%)	0
SUPRAVENTRICULAR ARRHYTHMIAS	0/422 (0%)	0	3/419 (0.7%)	3
DEEP VENOUS THROMBOSIS	1/422 (0.2%)	1	4/419 (1%)	4
ARTERIAL DISSECTION	0/422 (0%)	0	1/419 (0.2%)	1
ARTERIAL EMBOLUS	0/422 (0%)	0	1/419 (0.2%)	1
ACUTE CORONARY SYNDROME - UNSTABLE ANGINA	1/422 (0.2%)	1	0/419 (0%)	0
CHEST PAIN (INCLUDING ATYPICAL) WITHOUT MENTION OF CARDIAC ORIGEN	3/422 (0.7%)	3	4/419 (1%)	4
TROPONIN LEAK	1/422 (0.2%)	1	0/419 (0%)	0
VALVULAR HEART DISEASE	1/422 (0.2%)	1	1/419 (0.2%)	1
OTHER CARDIAC ARRHYTHMIAS	1/422 (0.2%)	1	2/419 (0.5%)	2
OTHER CARDIOVASCULAR DISORDER OR COMPLICATION	10/422 (2.4%)	10	13/419 (3.1%)	14
Gastrointestinal disorders
ABDOMINAL PAIN	1/422 (0.2%)	1	1/419 (0.2%)	1
GASTRIC OR DUODENAL ULCER	1/422 (0.2%)	1	0/419 (0%)	0
NAUSEA/VOMITING	1/422 (0.2%)	1	0/419 (0%)	0
GASTROINTESTINAL TRACT BLEEDING	7/422 (1.7%)	7	11/419 (2.6%)	12
DYSPHAGIA	2/422 (0.5%)	2	0/419 (0%)	0
PARALYTIC ILEUS/ BOWEL PSEUDO-OSTRUCTION	1/422 (0.2%)	1	0/419 (0%)	0
BOWEL OSBTRUCTION	1/422 (0.2%)	1	0/419 (0%)	0
OTHER DIGESTIVE DISORDER OR COMPLICATION	7/422 (1.7%)	10	9/419 (2.1%)	10
General disorders
FEVER	1/422 (0.2%)	1	2/419 (0.5%)	2
LOCALIZED PAIN	1/422 (0.2%)	1	1/419 (0.2%)	1
FAILURE TO THRIVE	3/422 (0.7%)	3	1/419 (0.2%)	1
OTHER SYSTEMIC ADVERSE EVENT OR COMPLICATION	0/422 (0%)	0	1/419 (0.2%)	1
OTHER UNCLASSIFIED ADVERSE EVENT	11/422 (2.6%)	12	4/419 (1%)	4
Immune system disorders
OROLINGUAL ANGIOEDEMA	2/422 (0.5%)	2	2/419 (0.5%)	2
Infections and infestations
BACTEREMIA	0/422 (0%)	0	1/419 (0.2%)	1
SEPTICEMIA OR SEPTIC SHOCK	3/422 (0.7%)	3	5/419 (1.2%)	6
PNEUMONIA	22/422 (5.2%)	26	12/419 (2.9%)	13
URINARY TRACT INFECTION	5/422 (1.2%)	8	9/419 (2.1%)	9
SURGICAL SITE INFECTION	4/422 (0.9%)	4	0/419 (0%)	0
CELLULITIS/NON-SURGICAL SKIN INFECTION	2/422 (0.5%)	2	2/419 (0.5%)	2
Injury, poisoning and procedural complications
SURGICAL WOUND HEMATOMA	1/422 (0.2%)	1	0/419 (0%)	0
OTHER NON-INFECTIOUS SURGICAL WOUND COMPLICATION	1/422 (0.2%)	1	0/419 (0%)	0
FALL	4/422 (0.9%)	4	1/419 (0.2%)	1
Metabolism and nutrition disorders
HYPOGLYCEMIA	1/422 (0.2%)	2	0/419 (0%)	0
HYPERGLYCEMIA	0/422 (0%)	0	1/419 (0.2%)	1
HYPONATREMIA	0/422 (0%)	0	2/419 (0.5%)	3
HYPOCALCEMIA	2/422 (0.5%)	2	0/419 (0%)	0
DEHYDRATION	2/422 (0.5%)	2	2/419 (0.5%)	2
OTHER ENDOCRINE OR METABOLIC DISORDER OR COMPLICATION	3/422 (0.7%)	3	0/419 (0%)	0
Musculoskeletal and connective tissue disorders
ARTHRITIS	0/422 (0%)	0	2/419 (0.5%)	2
FRACTURE	3/422 (0.7%)	3	4/419 (1%)	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT NEOPLASM (EXCEPT SKIN)	8/422 (1.9%)	8	8/419 (1.9%)	8
Nervous system disorders
RECURRENT STROKE NOT SPECIFIED AS HEMORRHAGE OR INFARCTION	16/422 (3.8%)	16	16/419 (3.8%)	19
DEPRESSION OF CONSCIOUSNESS	2/422 (0.5%)	2	0/419 (0%)	0
BRAIN ABSCESS OR ENCEPHALITIS	1/422 (0.2%)	1	0/419 (0%)	0
MENINGITIS OR VENTRICULITIS	0/422 (0%)	0	1/419 (0.2%)	1
TRANSIENT ISCHEMIC ATTACK	6/422 (1.4%)	8	10/419 (2.4%)	10
CEREBRAL INFARCTION	4/422 (0.9%)	4	12/419 (2.9%)	14
CEREBRAL EDEMA	16/422 (3.8%)	18	16/419 (3.8%)	16
SEIZURE	18/422 (4.3%)	23	15/419 (3.6%)	18
CONFUSION/ENCEPHALOPATHY/DELIRIUM	1/422 (0.2%)	1	1/419 (0.2%)	1
ANXIETY	3/422 (0.7%)	3	2/419 (0.5%)	2
HEADACHE	3/422 (0.7%)	3	6/419 (1.4%)	6
INCREASED INTRA-CRANIAL PRESSURE	1/422 (0.2%)	1	0/419 (0%)	0
PROGRESSION OF STROKE	15/422 (3.6%)	17	16/419 (3.8%)	17
OTHER NEUROLOGICAL DISORDER OR COMPLICATION	16/422 (3.8%)	17	13/419 (3.1%)	13
Psychiatric disorders
PSYCHIATRIC DEPRESSION	2/422 (0.5%)	3	1/419 (0.2%)	1
PSYCHIATRIC DISORDER	4/422 (0.9%)	4	1/419 (0.2%)	3
Renal and urinary disorders
HEMATURIA	0/422 (0%)	0	1/419 (0.2%)	1
RENAL INSUFFICIENCY	0/422 (0%)	0	1/419 (0.2%)	1
RENAL FAILURE	2/422 (0.5%)	2	3/419 (0.7%)	3
URINARY RETENTION	1/422 (0.2%)	1	0/419 (0%)	0
OTHER UROGENITAL DISORDER OR COMPLICATION	1/422 (0.2%)	1	5/419 (1.2%)	7
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) OR RESPIRATORY FAILURE	8/422 (1.9%)	8	4/419 (1%)	4
APNEA OR RESPIRATORY ARREST	1/422 (0.2%)	1	0/419 (0%)	0
RESPIRATORY INSUFFICIENCY	2/422 (0.5%)	2	2/419 (0.5%)	2
PLEURAL EFFUSION	1/422 (0.2%)	1	0/419 (0%)	0
SHORTNESS OF BREATH	1/422 (0.2%)	1	1/419 (0.2%)	1
OTHER RESPIRATORY DISORDER OR COMPLICATION	3/422 (0.7%)	3	5/419 (1.2%)	5
Skin and subcutaneous tissue disorders
DECUBITUS ULCERS/PRESSURE SORES	1/422 (0.2%)	1	1/419 (0.2%)	1
Vascular disorders
PULMONARY EMBOLISM	7/422 (1.7%)	7	5/419 (1.2%)	5
HYPERTENSION-NOT INTENDED	1/422 (0.2%)	1	1/419 (0.2%)	1
HYPOTENSION-NOT INTENDED	3/422 (0.7%)	3	5/419 (1.2%)	5
PRE-CEREBRAL OR CEREBRAL VASCULAR DISEASE (INCLUDING STENOSIS OR OCCLUSION)	10/422 (2.4%)	10	8/419 (1.9%)	8
SYNCOPE OR PRE-SYNCOPE	4/422 (0.9%)	8	7/419 (1.7%)	7
"HEMATOMA, NOT OTHERWISE SPECIFIED"	2/422 (0.5%)	2	1/419 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Albumin		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	352/422 (83.4%)		341/419 (81.4%)
Blood and lymphatic system disorders
SEPTICEMIA OR SEPTIC SHOCK	1/422 (0.2%)	1	3/419 (0.7%)	3
SYSTEMIC HEMORRHAGE	11/422 (2.6%)	12	11/419 (2.6%)	11
NON-CEREBRAL HEMORRHAGE	2/422 (0.5%)	2	1/419 (0.2%)	1
COAGULOPATHY	2/422 (0.5%)	2	2/419 (0.5%)	2
ANEMIA	39/422 (9.2%)	43	29/419 (6.9%)	34
POLYCYTEMIA	0/422 (0%)	0	1/419 (0.2%)	1
THROMBOCYTOPENIA	5/422 (1.2%)	5	4/419 (1%)	4
LEUKOPENIA	0/422 (0%)	0	1/419 (0.2%)	1
LEUKOCYTOSIS	15/422 (3.6%)	15	13/419 (3.1%)	14
TROMBOCYTOSIS	1/422 (0.2%)	1	0/419 (0%)	0
OTHER COAGULATION OR HEMATOLOGIC DISORDER OR COMPLICATION	5/422 (1.2%)	5	8/419 (1.9%)	9
RECURRENT STROKE NOT SPECIFIED AS HEMORRHAGE OR INFARCTION	0/422 (0%)	0	1/419 (0.2%)	1
SYMPTOMATIC INTRACRANIAL HEMORRHAGE	7/422 (1.7%)	7	6/419 (1.4%)	6
ASYMPTOMATIC INTRACRANIAL HEMORRHAGE	45/422 (10.7%)	48	35/419 (8.4%)	39
Cardiac disorders
ANGINA PECTORIS (STABLE)	2/422 (0.5%)	2	2/419 (0.5%)	2
ACUTE CORONARY SYNDROME - MYOCARDIAL INFARCTION	4/422 (0.9%)	4	0/419 (0%)	0
"CONGESTIVE HEART FAILURE, PULMONARY EDEMA"	41/422 (9.7%)	45	14/419 (3.3%)	14
VENTRICULAR FIBRILLATION OR TACHYCARDIA	2/422 (0.5%)	2	3/419 (0.7%)	3
ATRIAL FIBRILLATION/FLUTTER	40/422 (9.5%)	42	35/419 (8.4%)	36
BRADYCARDIA	27/422 (6.4%)	27	32/419 (7.6%)	34
TACHYCARDIA	12/422 (2.8%)	14	17/419 (4.1%)	17
"CONDUCTION BLOCKS (ATRIO-VENTRICULAR BLOCKS, BUNDLE-BRANCH BLOCKS)"	4/422 (0.9%)	5	1/419 (0.2%)	1
SUPRAVENTRICULAR ARRHYTHMIAS	6/422 (1.4%)	8	1/419 (0.2%)	1
CHEST PAIN (INCLUDING ATYPICAL) WITHOUT MENTION OF CARDIAC ORIGEN	4/422 (0.9%)	4	13/419 (3.1%)	15
TROPONIN LEAK	51/422 (12.1%)	53	20/419 (4.8%)	20
VALVULAR HEART DISEASE	6/422 (1.4%)	8	8/419 (1.9%)	16
OTHER CARDIAC ARRHYTHMIAS	12/422 (2.8%)	15	10/419 (2.4%)	13
OTHER CARDIOVASCULAR DISORDER OR COMPLICATION	23/422 (5.5%)	34	23/419 (5.5%)	31
Eye disorders
RETINAL VASCULAR ACCIDENT	1/422 (0.2%)	1	0/419 (0%)	0
Gastrointestinal disorders
ABDOMINAL PAIN	13/422 (3.1%)	13	15/419 (3.6%)	15
GASTRITIS/ ESOPHAGITIS/GERD	8/422 (1.9%)	8	7/419 (1.7%)	10
GASTRIC OR DUODENAL ULCER	0/422 (0%)	0	2/419 (0.5%)	2
NAUSEA/VOMITING	70/422 (16.6%)	81	48/419 (11.5%)	54
GASTROINTESTINAL TRACT BLEEDING	5/422 (1.2%)	5	7/419 (1.7%)	8
DIARRHEA	15/422 (3.6%)	15	9/419 (2.1%)	10
CONSTIPATION	30/422 (7.1%)	34	48/419 (11.5%)	51
FECAL INCONTINENCE	2/422 (0.5%)	2	2/419 (0.5%)	2
DYSPHAGIA	4/422 (0.9%)	4	2/419 (0.5%)	2
PARALYTIC ILEUS/ BOWEL PSEUDO-OSTRUCTION	0/422 (0%)	0	1/419 (0.2%)	1
BOWEL OSBTRUCTION	0/422 (0%)	0	1/419 (0.2%)	1
OTHER DIGESTIVE DISORDER OR COMPLICATION	33/422 (7.8%)	39	38/419 (9.1%)	49
General disorders
FEVER	38/422 (9%)	42	34/419 (8.1%)	35
LOCALIZED PAIN	54/422 (12.8%)	73	55/419 (13.1%)	78
GENERALIZED PAIN	9/422 (2.1%)	10	9/419 (2.1%)	9
FATIGUE	2/422 (0.5%)	2	2/419 (0.5%)	2
OTHER SYSTEMIC ADVERSE EVENT OR COMPLICATION	17/422 (4%)	18	12/419 (2.9%)	12
PERIPHERAL EDEMA	16/422 (3.8%)	19	16/419 (3.8%)	23
OTHER UNCLASSIFIED ADVERSE EVENT	40/422 (9.5%)	49	40/419 (9.5%)	54
Hepatobiliary disorders
"HEPATITIS, JAUNDICE, OR LIVER FAILURE"	0/422 (0%)	0	2/419 (0.5%)	2
Immune system disorders
OROLINGUAL ANGIOEDEMA	1/422 (0.2%)	1	1/419 (0.2%)	1
ALLERGIC REACTION TO STUDY DRUG	3/422 (0.7%)	3	2/419 (0.5%)	2
Infections and infestations
BACTEREMIA	3/422 (0.7%)	3	2/419 (0.5%)	2
PNEUMONIA	31/422 (7.3%)	33	23/419 (5.5%)	25
UPPER REPIRATORY INFECTION	9/422 (2.1%)	9	11/419 (2.6%)	11
BRONCHITIS	0/422 (0%)	0	1/419 (0.2%)	1
PHLEBITIS	1/422 (0.2%)	1	0/419 (0%)	0
URINARY TRACT INFECTION	73/422 (17.3%)	81	72/419 (17.2%)	83
CELLULITIS/NON-SURGICAL SKIN INFECTION	14/422 (3.3%)	16	11/419 (2.6%)	14
Injury, poisoning and procedural complications
ARTERIAL DISSECTION	1/422 (0.2%)	1	0/419 (0%)	0
CRANIAL NERVE INJURY	0/422 (0%)	0	1/419 (0.2%)	1
FRACTURE	4/422 (0.9%)	4	2/419 (0.5%)	2
INFILTRATION OF IV SITE	1/422 (0.2%)	1	4/419 (1%)	4
SURGICAL SITE INFECTION	2/422 (0.5%)	2	1/419 (0.2%)	1
SURGICAL WOUND HEMATOMA	2/422 (0.5%)	2	3/419 (0.7%)	3
OTHER NON-INFECTIOUS SURGICAL WOUND COMPLICATION	4/422 (0.9%)	4	5/419 (1.2%)	5
BLISTER	0/422 (0%)	0	2/419 (0.5%)	2
ACCIDENTAL TRAUMA	0/422 (0%)	0	1/419 (0.2%)	1
FALL	14/422 (3.3%)	15	13/419 (3.1%)	15
Investigations
EKG ABNORMALITIES	8/422 (1.9%)	8	7/419 (1.7%)	7
LIVER ENZYMES ELEVATION	6/422 (1.4%)	6	9/419 (2.1%)	9
OTHER ENZYME/S ELEVATION	3/422 (0.7%)	3	2/419 (0.5%)	3
Metabolism and nutrition disorders
FLUID OVERLOAD ALONE	4/422 (0.9%)	4	5/419 (1.2%)	5
HYPOGLYCEMIA	3/422 (0.7%)	3	6/419 (1.4%)	6
HYPERGLYCEMIA	34/422 (8.1%)	35	31/419 (7.4%)	31
DIABETES INSIPIDUS	0/422 (0%)	0	1/419 (0.2%)	1
DIABETES MELLITUS	2/422 (0.5%)	2	6/419 (1.4%)	6
HYPONATREMIA	5/422 (1.2%)	5	9/419 (2.1%)	9
HYPERNATREMIA	11/422 (2.6%)	11	4/419 (1%)	4
HYPOKALEMIA	93/422 (22%)	99	66/419 (15.8%)	72
HYPERKALEMIA	6/422 (1.4%)	6	1/419 (0.2%)	1
HYPERLIPIDEMIA	8/422 (1.9%)	8	21/419 (5%)	21
HYPOCALCEMIA	6/422 (1.4%)	6	11/419 (2.6%)	11
HYPERCALCEMIA	3/422 (0.7%)	3	0/419 (0%)	0
HYPOMAGNESEMIA	18/422 (4.3%)	19	18/419 (4.3%)	18
DEHYDRATION	5/422 (1.2%)	5	4/419 (1%)	4
ACID-BASE IMBALANCE	2/422 (0.5%)	2	2/419 (0.5%)	2
HYPOCHLOREMIA	0/422 (0%)	0	3/419 (0.7%)	3
HYPERCHLOREMIA	2/422 (0.5%)	2	4/419 (1%)	4
OTHER ENDOCRINE OR METABOLIC DISORDER OR COMPLICATION	36/422 (8.5%)	47	42/419 (10%)	63
Musculoskeletal and connective tissue disorders
ARTHRITIS	2/422 (0.5%)	2	3/419 (0.7%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT NEOPLASM (EXCEPT SKIN)	1/422 (0.2%)	1	0/419 (0%)	0
MALIGNANT NEOPLASM (SKIN)	1/422 (0.2%)	1	0/419 (0%)	0
Nervous system disorders
DIZZINESS	6/422 (1.4%)	6	9/419 (2.1%)	9
DEPRESSION OF CONSCIOUSNESS	10/422 (2.4%)	11	7/419 (1.7%)	7
CEREBRAL INFARCTION	0/422 (0%)	0	1/419 (0.2%)	1
CEREBRAL EDEMA	8/422 (1.9%)	10	10/419 (2.4%)	11
SEIZURE	10/422 (2.4%)	10	7/419 (1.7%)	9
HEADACHE	81/422 (19.2%)	92	76/419 (18.1%)	84
AGITATION	15/422 (3.6%)	16	22/419 (5.3%)	24
INCREASED INTRA-CRANIAL PRESSURE	1/422 (0.2%)	1	0/419 (0%)	0
PROGRESSION OF STROKE	18/422 (4.3%)	18	9/419 (2.1%)	9
OTHER NEUROLOGICAL DISORDER OR COMPLICATION	31/422 (7.3%)	38	39/419 (9.3%)	46
Psychiatric disorders
CONFUSION/ENCEPHALOPATHY/DELIRIUM	5/422 (1.2%)	5	6/419 (1.4%)	6
ANXIETY	9/422 (2.1%)	9	12/419 (2.9%)	12
APHASIA	1/422 (0.2%)	2	1/419 (0.2%)	1
PSYCHIATRIC DEPRESSION	32/422 (7.6%)	34	35/419 (8.4%)	35
INSOMNIA	19/422 (4.5%)	19	29/419 (6.9%)	30
PSYCHIATRIC DISORDER	2/422 (0.5%)	2	5/419 (1.2%)	5
Renal and urinary disorders
HEMATURIA	19/422 (4.5%)	19	18/419 (4.3%)	18
RENAL INSUFFICIENCY	11/422 (2.6%)	12	8/419 (1.9%)	9
RENAL FAILURE	2/422 (0.5%)	2	3/419 (0.7%)	3
UROGENITAL INCONTINENCE (WAS 410)	6/422 (1.4%)	6	5/419 (1.2%)	5
URINARY RETENTION	11/422 (2.6%)	13	12/419 (2.9%)	13
OTHER UROGENITAL DISORDER OR COMPLICATION	21/422 (5%)	23	25/419 (6%)	31
Reproductive system and breast disorders
CRAMPING	7/422 (1.7%)	7	6/419 (1.4%)	7
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) OR RESPIRATORY FAILURE	3/422 (0.7%)	4	3/419 (0.7%)	3
BRONCHOSPASM	6/422 (1.4%)	6	8/419 (1.9%)	8
HYPOXEMIA	5/422 (1.2%)	5	4/419 (1%)	4
HYPERCARBIA	1/422 (0.2%)	1	1/419 (0.2%)	1
CRACKLES/RALES	3/422 (0.7%)	3	5/419 (1.2%)	6
APNEA OR RESPIRATORY ARREST	2/422 (0.5%)	2	0/419 (0%)	0
TACHYPNEA	8/422 (1.9%)	8	7/419 (1.7%)	7
RESPIRATORY INSUFFICIENCY	1/422 (0.2%)	1	0/419 (0%)	0
PLEURAL EFFUSION	9/422 (2.1%)	10	7/419 (1.7%)	9
SHORTNESS OF BREATH	12/422 (2.8%)	13	7/419 (1.7%)	7
COUGH	8/422 (1.9%)	9	11/419 (2.6%)	11
OTHER RESPIRATORY DISORDER OR COMPLICATION	33/422 (7.8%)	45	36/419 (8.6%)	49
Skin and subcutaneous tissue disorders
RASH	16/422 (3.8%)	16	14/419 (3.3%)	16
ITCHING	2/422 (0.5%)	2	5/419 (1.2%)	5
ECCHYMOSIS	16/422 (3.8%)	18	25/419 (6%)	29
DECUBITUS ULCERS/PRESSURE SORES	3/422 (0.7%)	3	8/419 (1.9%)	9
DERMATITIS	4/422 (0.9%)	5	6/419 (1.4%)	6
Vascular disorders
PULMONARY EMBOLISM	1/422 (0.2%)	1	0/419 (0%)	0
DEEP VENOUS THROMBOSIS	6/422 (1.4%)	6	11/419 (2.6%)	12
SUPERFICIAL VENOUS THROMBOSIS	2/422 (0.5%)	2	2/419 (0.5%)	2
ARTERIAL THROMBOSIS	0/422 (0%)	0	1/419 (0.2%)	1
HYPERTENSION-NOT INTENDED	39/422 (9.2%)	42	29/419 (6.9%)	31
HYPOTENSION-NOT INTENDED	19/422 (4.5%)	21	33/419 (7.9%)	36
PRE-CEREBRAL OR CEREBRAL VASCULAR DISEASE (INCLUDING STENOSIS OR OCCLUSION)	6/422 (1.4%)	6	5/419 (1.2%)	5
TRANSIENT ISCHEMIC ATTACK	2/422 (0.5%)	3	3/419 (0.7%)	3
SYNCOPE OR PRE-SYNCOPE	3/422 (0.7%)	3	3/419 (0.7%)	3
"HEMATOMA, NOT OTHERWISE SPECIFIED"	12/422 (2.8%)	12	8/419 (1.9%)	10

Limitations/Caveats

[Not Specified]

More Information

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.