Albumin in Acute Ischemic Stroke Trial

NCT ID: NCT00235495

Last Updated: 2019-12-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 841 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2013-02-28

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.]

Conditions

Ischemic Stroke

Keywords

stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Albumin (ALB)

Albumin (human albumin, 25% solution, 2.0 g/kg), infused intravenously over a period of 2 hours

Group Type: ACTIVE_COMPARATOR

Albumin

Intervention Type: BIOLOGICAL

human albumin, 25%, 2.0g/kg intravenously (or equivalent volume of saline control), infused over 2 h, commencing within 5 hours of stroke onset

Saline

Saline (isotonic solution), 8 ml/kg, infused intravenously over a 2-hour period

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

equivalent volume of isotonic saline control

Interventions

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

Intervention Type: BIOLOGICAL

Saline

equivalent volume of isotonic saline control

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 83 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

University of Calgary

OTHER

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: collaborator

Neurological Emergencies Treatment Trials Network (NETT)

NETWORK

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Myron Ginsberg

Principal Investigator; Peritz Scheinberg Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Myron D. Ginsberg, MD

Role: STUDY_CHAIR

University of Miami

Michael D. Hill, MD MSc

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Yuko Y Palesch, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

Mayo Clinic Hospital

Phoenix, Arizona, United States

University of Arizona Medical Center-South Campus

Tucson, Arizona, United States

University of Arizona Medical Center

Tucson, Arizona, United States

John Muir Medical Ctr-Concord

Concord, California, United States

El Camino Hospital

Mountain View, California, United States

UCSF Medical Center

San Francisco, California, United States

UCSF-San Francisco General Hospital

San Francisco, California, United States

California Pacific Medical Center, Davies Campus

San Francisco, California, United States

California Pacific Medical Center, Pacific Campus

San Francisco, California, United States

O'Connor Hospital

San Jose, California, United States

UCLA Medical Center, Santa Monica

Santa Monica, California, United States

Stanford University Medical Center

Stanford, California, United States

John Muir Medical Ctr-Walnut Creek

Walnut Creek, California, United States

Yale University School of Medicine

New Haven, Connecticut, United States

Christiana Hospital

Newark, Delaware, United States

University of Florida/Shands

Jacksonville, Florida, United States

Jackson Memorial Hospital, University of Miami

Miami, Florida, United States

The Villages Research Group

Ocala, Florida, United States

Neuroscience Research Institute at Florida Hospital Orlando

Orlando, Florida, United States

Intercoastal Neurology/Medical Research Center

Sarasota, Florida, United States

Grady Memorial Hospital

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Loyola University Medical Center

Maywood, Illinois, United States

St. Elizabeth Medical Center South

Edgewood, Kentucky, United States

St. Elizabeth Hospital

Florence, Kentucky, United States

University of Kentucky Hospital

Lexington, Kentucky, United States

University of Maryland Medical Center

Baltimore, Maryland, United States

Upper Chesapeake Medical Center

Bel Air, Maryland, United States

Detroit Receiving Hospital

Detroit, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

Sinai-Grace Hospital

Detroit, Michigan, United States

William Beaumont Hospital

Royal Oak, Michigan, United States

Fairview Southdale Hospital

Edina, Minnesota, United States

Hennepin County Medical Center

Minneapolis, Minnesota, United States

University of Minnesota Medical Center Fairview

Minneapolis, Minnesota, United States

HealthEast Care System/St. Joseph's Hospital

Saint Paul, Minnesota, United States

Saint Louis University

St Louis, Missouri, United States

Atlantic Neuroscience Institute, Overlook Hospital

Summit, New Jersey, 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

Winthrop University Hospital

Mineola, New York, United States

Columbia University Medical Center

New York, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Wake Med Health and Hospitals

Raleigh, North Carolina, United States

Christ Hospital

Cincinnati, Ohio, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Good Samaritan Hospital

Cincinnati, Ohio, United States

Bethesda North Hospital

Cincinnati, Ohio, United States

MetroHealth Medical Center

Cleveland, Ohio, United States

Ohio State University Medical Center

Columbus, Ohio, United States

Mercy Health Fairfield Hospital

Fairfield, Ohio, United States

Providence Portland Medical Center

Portland, Oregon, United States

Providence St. Vincent Medical Center

Portland, Oregon, United States

OHSU Legacy Emmanuel Hospital

Portland, Oregon, United States

Oregon Health & Science University

Portland, Oregon, United States

Sacred Heart Medical Center

Springfield, Oregon, United States

Abington Memorial Hospital

Abington, Pennsylvania, United States

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, United States

Temple University Hospital

Philadelphia, Pennsylvania, United States

Hahnemann University Hospital

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Seton Medical Center

Austin, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Memorial Hermann Texas Medical Center

Houston, Texas, United States

Virginia Commonwealth University Medical Center

Richmond, Virginia, United States

Froedtert Memorial Hospital

Milwaukee, Wisconsin, United States

Foothills Hospital, University of Calgary

Calgary, Alberta, Canada

University of Alberta

Edmonton, Alberta, Canada

Grey Nuns Community Hospital

Edmonton, Alberta, Canada

Royal Island Hospital

Kamloops, British Columbia, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

Queen Elizabeth II Health Science Centre

Halifax, Nova Scotia, Canada

London Health Sciences Centre-University Hospital

London, Ontario, Canada

Trillium Health Centre

Mississauga, Ontario, Canada

The Ottawa Hospital

Ottawa, Ontario, Canada

Thunder Bay Regional Health Sciences Centre

Thunder Bay, Ontario, Canada

University of Toronto, St. Michael's Hospital

Toronto, Ontario, Canada

Hopital Charles LeMoyne, Centre de Recherche

Greenfield Park, Quebec, Canada

Centre de Sante et de Service Sociaux de Chicoutimi

Saguenay, Quebec, Canada

Helsinki University Central Hospital

Helsinki, , Finland

Tampere University Hospital

Tampere, , Finland

Hadassah Medical Organization, Hadassah University Hospital

‘En Kerem, Jerusalem, Israel

Chaim Sheba Medical Center at Tel-Hashomer

Tel Litwinsky, Ramat Gan, Israel

Soroka Medical Center

Beersheba, , Israel

Rambam Health Care Campus

Haifa, , Israel

Tel-Aviv Sourasky Medical Center

Tel Aviv, , Israel

Countries

United States; Canada; Finland; Israel

References

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.

Reference Type: DERIVED

PMID: 27462118 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26325387 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24076337 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21546491 (View on PubMed)

Other Identifiers

U01NS054630

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIH NINDS 5U01 NS040406-08

Identifier Type: OTHER

Identifier Source: secondary_id

20060233

Identifier Type: OTHER

Identifier Source: secondary_id

20060083

Identifier Type: -

Identifier Source: org_study_id