Clinical trial NCT00235495: Albumin in Acute Ischemic Stroke Trial
Official title: A Phase III Randomized Multicenter Clinical Trial Of High-Dose Human Albumin Therapy For Neuroprotection In Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Ischemic Stroke
Keywords: stroke
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: University of Calgary
name: Medical University of South Carolina
name: Neurological Emergencies Treatment Trials Network (NETT)
First posted: 2005-10-10
Enrollment: 841
Sex: ALL
Minimum age (years): 18
Maximum age (years): 83
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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. \[The current trial is termed "Part 2" and incorporates revisions to the initial protocol that were instituted after the Data Safety Monitoring Board (DSMB) suspended subject recruitment because of a safety concern after 434 subjects had been enrolled. The protocol revisions of Part 2 resulted from the study team's thorough review of the Part-1 safety data and were designed to optimize safety going forward.\]

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: at 3 months
Secondary outcomes:
measure: 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
timeFrame: at 3 months
measure: Number of Participants With a NIHSS of 0-1 at 24 Hours
timeFrame: at 24 hours
measure: Number of Participants With a NIHSS 0-1 at 90 Days.
timeFrame: at 90 days
measure: The Number of Participants With a Score on the mRS 0-1 at 90 Days.
timeFrame: at 90 days
measure: The Number of Participants With a Score on the mRS of 0-2 at 90 Days.
timeFrame: at 90 days
measure: Number of Participants With a Favorable Outcome Per Modified Rankin Scare (mRS)
timeFrame: 90 days
measure: Barthel Index (BI) 95-100
timeFrame: at 90 days
measure: Number of Participants With an EuroQol (EQ-5D) Favorable Score < 0.78
timeFrame: at 90 days
measure: Number of Participants With a Stroke Specific Quality of Life Scale (SSQOL) Score of >=3
timeFrame: at 90 days
measure: Trailmaking A
timeFrame: at 90 days
measure: Trailmaking B
timeFrame: at 90 days
measure: Number of Participants With Neurological Deterioration Within 48 Hours
timeFrame: within 48 hours
measure: Neurological Death Within 7 Days
timeFrame: within 7 days
measure: Recurrent Ischemic Stroke Within 30 Days
timeFrame: within 30 days
measure: Atrial Fibrillation Within 48 Hours
timeFrame: within 48 hours
measure: Pulmonary Edema Within 48 Hours
timeFrame: within 48 hours
measure: Shortness of Breath Within 48 Hours
timeFrame: within 48 hours
measure: Symptomatic Intracerebral Hemorrhage (ICH) Within 24 Hours
timeFrame: within 24 hours
measure: Asymptomatic ICH Within 24 Hours
timeFrame: within 24 hours
measure: Death Within 30 Days
timeFrame: within 30 days
measure: Death Within 90 Days
timeFrame: within 90 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Medical Center-South Campus
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Medical Center
state: Arizona
city: Concord
country: United States
facility: John Muir Medical Ctr-Concord
state: California
city: Mountain View
country: United States
facility: El Camino Hospital
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF-San Francisco General Hospital
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center, Davies Campus
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center, Pacific Campus
state: California
city: San Jose
country: United States
facility: O'Connor Hospital
state: California
city: Santa Monica
country: United States
facility: UCLA Medical Center, Santa Monica
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Walnut Creek
country: United States
facility: John Muir Medical Ctr-Walnut Creek
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Newark
country: United States
facility: Christiana Hospital
state: Delaware
city: Jacksonville
country: United States
facility: University of Florida/Shands
state: Florida
city: Miami
country: United States
facility: Jackson Memorial Hospital, University of Miami
state: Florida
city: Ocala
country: United States
facility: The Villages Research Group
state: Florida
city: Orlando
country: United States
facility: Neuroscience Research Institute at Florida Hospital Orlando
state: Florida
city: Sarasota
country: United States
facility: Intercoastal Neurology/Medical Research Center
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Edgewood
country: United States
facility: St. Elizabeth Medical Center South
state: Kentucky
city: Florence
country: United States
facility: St. Elizabeth Hospital
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky Hospital
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Bel Air
country: United States
facility: Upper Chesapeake Medical Center
state: Maryland
city: Detroit
country: United States
facility: Detroit Receiving Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Detroit
country: United States
facility: Sinai-Grace Hospital
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center Fairview
state: Minnesota
city: Saint Paul
country: United States
facility: HealthEast Care System/St. Joseph's Hospital
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Summit
country: United States
facility: Atlantic Neuroscience Institute, Overlook Hospital
state: New Jersey
city: Brooklyn
country: United States
facility: New York Methodist Hospital
state: New York
city: Buffalo
country: United States
facility: Buffalo General Medical Center
state: New York
city: Buffalo
country: United States
facility: Mercy Hospital of Buffalo
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Wake Med Health and Hospitals
state: North Carolina
city: Cincinnati
country: United States
facility: Christ Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Bethesda North Hospital
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Fairfield
country: United States
facility: Mercy Health Fairfield Hospital
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Portland
country: United States
facility: OHSU Legacy Emmanuel Hospital
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Springfield
country: United States
facility: Sacred Heart Medical Center
state: Oregon
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hahnemann University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Austin
country: United States
facility: Seton Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Texas Medical Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Milwaukee
country: United States
facility: Froedtert Memorial Hospital
state: Wisconsin
city: Calgary
country: Canada
facility: Foothills Hospital, University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Edmonton
country: Canada
facility: Grey Nuns Community Hospital
state: Alberta
city: Kamloops
country: Canada
facility: Royal Island Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Science Centre
state: Nova Scotia
city: London
country: Canada
facility: London Health Sciences Centre-University Hospital
state: Ontario
city: Mississauga
country: Canada
facility: Trillium Health Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Thunder Bay
country: Canada
facility: Thunder Bay Regional Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University of Toronto, St. Michael's Hospital
state: Ontario
city: Greenfield Park
country: Canada
facility: Hopital Charles LeMoyne, Centre de Recherche
state: Quebec
city: Saguenay
country: Canada
facility: Centre de Sante et de Service Sociaux de Chicoutimi
state: Quebec
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Ein Kerem
country: Israel
facility: Hadassah Medical Organization, Hadassah University Hospital
state: Jerusalem
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center at Tel-Hashomer
state: Ramat Gan
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
Study officials:
affiliation: University of Miami
name: Myron D. Ginsberg, MD
role: STUDY_CHAIR
affiliation: University of Calgary
name: Michael D. Hill, MD MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina
name: Yuko Y Palesch, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Martin RH, Yeatts SD, Hill MD, Moy CS, Ginsberg MD, Palesch YY; ALIAS Parts 1 and 2 and NETT Investigators. ALIAS (Albumin in Acute Ischemic Stroke) Trials: Analysis of the Combined Data From Parts 1 and 2. Stroke. 2016 Sep;47(9):2355-9. doi: 10.1161/STROKEAHA.116.012825. Epub 2016 Jul 26.
citation: Hill MD, Martin RH, Palesch YY, Moy CS, Tamariz D, Ryckborst KJ, Jones EB, Weisman D, Pettigrew C, Ginsberg MD. Albumin Administration in Acute Ischemic Stroke: Safety Analysis of the ALIAS Part 2 Multicenter Trial. PLoS One. 2015 Sep 1;10(9):e0131390. doi: 10.1371/journal.pone.0131390. eCollection 2015.
citation: Ginsberg MD, Palesch YY, Hill MD, Martin RH, Moy CS, Barsan WG, Waldman BD, Tamariz D, Ryckborst KJ; ALIAS and Neurological Emergencies Treatment Trials (NETT) Investigators. High-dose albumin treatment for acute ischaemic stroke (ALIAS) Part 2: a randomised, double-blind, phase 3, placebo-controlled trial. Lancet Neurol. 2013 Nov;12(11):1049-58. doi: 10.1016/S1474-4422(13)70223-0. Epub 2013 Sep 27.
citation: Hill MD, Martin RH, Palesch YY, Tamariz D, Waldman BD, Ryckborst KJ, Moy CS, Barsan WG, Ginsberg MD; ALIAS Investigators; Neurological Emergencies Treatment Trials Network. The Albumin in Acute Stroke Part 1 Trial: an exploratory efficacy analysis. Stroke. 2011 Jun;42(6):1621-5. doi: 10.1161/STROKEAHA.110.610980. Epub 2011 May 5.