Albumin in Acute Ischemic Stroke Trial

Ischemic Stroke Clinical Trial

— ALIAS  

Official title:

A Phase III Randomized Multicenter Clinical Trial Of High-Dose Human Albumin Therapy For Neuroprotection In Acute Ischemic Stroke

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00235495
• Other study ID #: 20060083
• Secondary ID: U01NS054630NIH N
• Status: Terminated
• Phase: Phase 3
• Start date: June 2006
• Est. completion date: February 2013

Study information

• Verified date: December 2019
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.]

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 841
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 83 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

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

Drug:
• Saline
equivalent volume of isotonic saline control

Locations

Country	Name	City	State
Canada	Foothills Hospital, University of Calgary	Calgary	Alberta
Canada	Grey Nuns Community Hospital	Edmonton	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	Hopital Charles LeMoyne, Centre de Recherche	Greenfield Park	Quebec
Canada	Queen Elizabeth II Health Science Centre	Halifax	Nova Scotia
Canada	Royal Island Hospital	Kamloops	British Columbia
Canada	London Health Sciences Centre-University Hospital	London	Ontario
Canada	Trillium Health Centre	Mississauga	Ontario
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Centre de Sante et de Service Sociaux de Chicoutimi	Saguenay	Quebec
Canada	Thunder Bay Regional Health Sciences Centre	Thunder Bay	Ontario
Canada	University of Toronto, St. Michael's Hospital	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Finland	Helsinki University Central Hospital	Helsinki
Finland	Tampere University Hospital	Tampere
Israel	Soroka Medical Center	Beer Sheva
Israel	Hadassah Medical Organization, Hadassah University Hospital	Ein Kerem	Jerusalem
Israel	Rambam Health Care Campus	Haifa
Israel	Tel-Aviv Sourasky Medical Center	Tel Aviv
Israel	Chaim Sheba Medical Center at Tel-Hashomer	Tel Hashomer	Ramat Gan
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Emory University Hospital	Atlanta	Georgia
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	Seton Medical Center	Austin	Texas
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Upper Chesapeake Medical Center	Bel Air	Maryland
United States	New York Methodist Hospital	Brooklyn	New York
United States	Buffalo General Medical Center	Buffalo	New York
United States	Mercy Hospital of Buffalo	Buffalo	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Christ Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital	Cincinnati	Ohio
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Ohio State University Medical Center	Columbus	Ohio
United States	John Muir Medical Ctr-Concord	Concord	California
United States	Detroit Receiving Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Sinai-Grace Hospital	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	St. Elizabeth Medical Center South	Edgewood	Kentucky
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Mercy Health Fairfield Hospital	Fairfield	Ohio
United States	St. Elizabeth Hospital	Florence	Kentucky
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	Baylor College of Medicine	Houston	Texas
United States	Memorial Hermann Texas Medical Center	Houston	Texas
United States	University of Florida/Shands	Jacksonville	Florida
United States	University of Kentucky Hospital	Lexington	Kentucky
United States	Loyola University Medical Center	Maywood	Illinois
United States	Jackson Memorial Hospital, University of Miami	Miami	Florida
United States	Froedtert Memorial Hospital	Milwaukee	Wisconsin
United States	Winthrop University Hospital	Mineola	New York
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	University of Minnesota Medical Center Fairview	Minneapolis	Minnesota
United States	El Camino Hospital	Mountain View	California
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Christiana Hospital	Newark	Delaware
United States	The Villages Research Group	Ocala	Florida
United States	Neuroscience Research Institute at Florida Hospital Orlando	Orlando	Florida
United States	Hahnemann University Hospital	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	OHSU Legacy Emmanuel Hospital	Portland	Oregon
United States	Oregon Health & Science University	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Wake Med Health and Hospitals	Raleigh	North Carolina
United States	Virginia Commonwealth University Medical Center	Richmond	Virginia
United States	William Beaumont Hospital	Royal Oak	Michigan
United States	Saint Louis University	Saint Louis	Missouri
United States	HealthEast Care System/St. Joseph's Hospital	Saint Paul	Minnesota
United States	California Pacific Medical Center, Davies Campus	San Francisco	California
United States	California Pacific Medical Center, Pacific Campus	San Francisco	California
United States	UCSF Medical Center	San Francisco	California
United States	UCSF-San Francisco General Hospital	San Francisco	California
United States	O'Connor Hospital	San Jose	California
United States	UCLA Medical Center, Santa Monica	Santa Monica	California
United States	Intercoastal Neurology/Medical Research Center	Sarasota	Florida
United States	Sacred Heart Medical Center	Springfield	Oregon
United States	Stanford University Medical Center	Stanford	California
United States	Atlantic Neuroscience Institute, Overlook Hospital	Summit	New Jersey
United States	University of Arizona Medical Center	Tucson	Arizona
United States	University of Arizona Medical Center-South Campus	Tucson	Arizona
United States	John Muir Medical Ctr-Walnut Creek	Walnut Creek	California

Sponsors (5)

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

Countries where clinical trial is conducted

United States,  Canada,  Finland,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.	at 3 months
Secondary	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
Secondary	Number of Participants With a NIHSS of 0-1 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.	at 24 hours
Secondary	Number of Participants With a NIHSS 0-1 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.	at 90 days
Secondary	The Number of Participants With a Score on the mRS 0-1 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.	at 90 days
Secondary	The Number of Participants With a Score on the mRS of 0-2 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.	at 90 days
Secondary	Number of Participants With a Favorable Outcome Per Modified Rankin Scare (mRS)	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.	90 days
Secondary	Barthel Index (BI) 95-100	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.	at 90 days
Secondary	Number of Participants With an EuroQol (EQ-5D) Favorable Score < 0.78	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.	at 90 days
Secondary	Number of Participants With a Stroke Specific Quality of Life Scale (SSQOL) Score of >=3	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.	at 90 days
Secondary	Trailmaking A	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.	at 90 days
Secondary	Trailmaking B	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.	at 90 days
Secondary	Number of Participants With Neurological Deterioration Within 48 Hours	This is assessed as the number of participants with a neurological adverse event.	within 48 hours
Secondary	Neurological Death Within 7 Days		within 7 days
Secondary	Recurrent Ischemic Stroke Within 30 Days		within 30 days
Secondary	Atrial Fibrillation Within 48 Hours		within 48 hours
Secondary	Pulmonary Edema Within 48 Hours		within 48 hours
Secondary	Shortness of Breath Within 48 Hours		within 48 hours
Secondary	Symptomatic Intracerebral Hemorrhage (ICH) Within 24 Hours		within 24 hours
Secondary	Asymptomatic ICH Within 24 Hours		within 24 hours
Secondary	Death Within 30 Days		within 30 days
Secondary	Death Within 90 Days		within 90 days