Treatment of Subarachnoid Hemorrhage With Human Albumin

NCT00283400 | Terminated Results DMC

• 1 other identifier: R01NS049135
• Study Type: interventional
• Target: 47
• Locations: 2 countries
• Sites: 6

Brief Summary

The purpose of this study is to evaluate the tolerability and safety of 25 percent human albumin therapy in patients with subarachnoid hemorrhage.

Conditions

Subarachnoid Hemorrhage

Keywords

subarachnoid hemorrhage; SAH; human albumin; HA; cerebral vasospasm; aneurysm; neuroprotective

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of the 25% Human Albumin Dosages and the Functional Outcome.

  Tolerability outcome: Subject's ability to receive the full allocated human albumin dose without incurring frank congestive heart failure or experiencing anaphylactic reactions that required discontinuation of the treatment. Study would be terminated if 2 or more subjects developed severe or life-threatening heart failure considered to be related (probably, possibly, and definitely) to albumin treatment.

  9 days after enrollment

Secondary Outcomes (2)

• Serious Adverse Events

  within 3 months after enrollment

• Good Clinical Outcome Was Defined as a Glasgow Outcome Scale Score of 0-1

  3 months after enrollment

Study Arms (4)

dosage tier 1

ACTIVE COMPARATOR

0.625 g/kg 25% human albumin

Drug: 25% human albumin

dosage tier 2

ACTIVE COMPARATOR

1.25 g/kg 25% human albumin

Drug: 25% human albumin

dosage tier 3

ACTIVE COMPARATOR

1.875 g/kg 25% human albumin

Drug: 25% human albumin

dosage tier 4

ACTIVE COMPARATOR

2.5 g/kg 25% human albumin

Drug: 25% human albumin

Interventions

25% human albumin DRUG

25% human albumin: after approval by the Data and Safety Monitoring Board dosage tier would be escalated to the subsequent higher level sequentially.

dosage tier 1; dosage tier 2; dosage tier 3; dosage tier 4

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients (male or female) were at least 18 but younger than 80 years of age.
• Onset of new neurological signs of subarachnoid hemorrhage within 72 hours at the time of evaluation and initiation of treatment with 25% human albumin.
• Clinical signs consistent with the diagnosis of subarachnoid hemorrhage including severe thunderclap headache, cranial nerve abnormalities, decreased level of consciousness, meningismus and focal neurological deficits.
• Computed tomography demonstrated subarachnoid hemorrhage.
• Cerebral angiography revealed the presence of saccular aneurysm(s) in a location that explains the subarachnoid hemorrhage.
• Treatment of cerebral aneurysm was carried out prior to initiation of HA infusion but within 72 hours of symptom onset. Accepted treatments of aneurysms include surgical clipping or endovascular embolization.

You may not qualify if:

• Time of symptom onset could be reliably assessed.
• No demonstrable aneurysm by cerebral angiography.
• Evidence of traumatic, mycotic, or fusiform aneurysm by cerebral angiography.
• World Federation of Neurological Surgeons scale of IV and V
• Computed tomography scale of 0-1
• History within the past 6 months, and/or physical findings on admission of decompensated congestive heart failure (NYHA Class IV or congestive heart failure requiring hospitalization).
• Patient received albumin prior to treatment assignment during the present admission.
• Hospitalization for or diagnosis of acute myocardial infarction within the preceding 3 months.
• Symptoms or electrocardiographic signs indicative of acute myocardial infarction on admission.
• Electrocardiographic evidence and/or physical findings compatible with second- or third-degree heart block, or of cardiac arrhythmia associated with hemodynamic instability.
• Echocardiogram performed before treatment revealing a left ventricular ejection fraction ≤ 40% (if available).
• Serum creatinine \> 2.0 mg/dl or creatinine clearance \< 50 ml/min.
• Pregnancy, lactation or parturition within previous 30 days.
• Allergy to albumin.
• Severe prior physical disability that precludes evaluation of clinical outcome measures.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (6)

The Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Penn State University

Hershey, Pennsylvania, 17033, United States

Location

Data Coordination Unit, Department of Biostatistics, Bioinformatics and Epidemiology, at the Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Calgary

Calgary, Alberta, Canada

Location

University of Toronto

Toronto, Ontario, Canada

Location

Related Publications (11)

• Suarez JI, Shannon L, Zaidat OO, Suri MF, Singh G, Lynch G, Selman WR. Effect of human albumin administration on clinical outcome and hospital cost in patients with subarachnoid hemorrhage. J Neurosurg. 2004 Apr;100(4):585-90. doi: 10.3171/jns.2004.100.4.0585.

  PMID: 15070109 BACKGROUND

• Suarez JI, Qureshi AI, Yahia AB, Parekh PD, Tamargo RJ, Williams MA, Ulatowski JA, Hanley DF, Razumovsky AY. Symptomatic vasospasm diagnosis after subarachnoid hemorrhage: evaluation of transcranial Doppler ultrasound and cerebral angiography as related to compromised vascular distribution. Crit Care Med. 2002 Jun;30(6):1348-55. doi: 10.1097/00003246-200206000-00035.

  PMID: 12072693 BACKGROUND

• Lennihan L, Mayer SA, Fink ME, Beckford A, Paik MC, Zhang H, Wu YC, Klebanoff LM, Raps EC, Solomon RA. Effect of hypervolemic therapy on cerebral blood flow after subarachnoid hemorrhage : a randomized controlled trial. Stroke. 2000 Feb;31(2):383-91. doi: 10.1161/01.str.31.2.383.

  PMID: 10657410 BACKGROUND

• Haley EC Jr, Kassell NF, Torner JC. A randomized controlled trial of high-dose intravenous nicardipine in aneurysmal subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study. J Neurosurg. 1993 Apr;78(4):537-47. doi: 10.3171/jns.1993.78.4.0537.

  PMID: 8450326 BACKGROUND

• Wilkes MM, Navickis RJ. Patient survival after human albumin administration. A meta-analysis of randomized, controlled trials. Ann Intern Med. 2001 Aug 7;135(3):149-64. doi: 10.7326/0003-4819-135-3-200108070-00007.

  PMID: 11487482 BACKGROUND

• Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R; SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004 May 27;350(22):2247-56. doi: 10.1056/NEJMoa040232.

  PMID: 15163774 BACKGROUND

• Belayev L, Liu Y, Zhao W, Busto R, Ginsberg MD. Human albumin therapy of acute ischemic stroke: marked neuroprotective efficacy at moderate doses and with a broad therapeutic window. Stroke. 2001 Feb;32(2):553-60. doi: 10.1161/01.str.32.2.553.

  PMID: 11157196 BACKGROUND

• Osterloh K, Ewert U, Pries AR. Interaction of albumin with the endothelial cell surface. Am J Physiol Heart Circ Physiol. 2002 Jul;283(1):H398-405. doi: 10.1152/ajpheart.00558.2001.

  PMID: 12063314 BACKGROUND

• Zhang WJ, Frei B. Albumin selectively inhibits TNF alpha-induced expression of vascular cell adhesion molecule-1 in human aortic endothelial cells. Cardiovasc Res. 2002 Sep;55(4):820-9. doi: 10.1016/s0008-6363(02)00492-3.

  PMID: 12176131 BACKGROUND

• Suarez JI, Martin RH, Calvillo E, Dillon C, Bershad EM, Macdonald RL, Wong J, Harbaugh R; ALISAH Investigators. The Albumin in Subarachnoid Hemorrhage (ALISAH) multicenter pilot clinical trial: safety and neurologic outcomes. Stroke. 2012 Mar;43(3):683-90. doi: 10.1161/STROKEAHA.111.633958. Epub 2012 Jan 19.

  PMID: 22267829 RESULT

• Suarez JI, Martin RH, Calvillo E, Bershad EM, Venkatasubba Rao CP. Effect of human albumin on TCD vasospasm, DCI, and cerebral infarction in subarachnoid hemorrhage: the ALISAH study. Acta Neurochir Suppl. 2015;120:287-90. doi: 10.1007/978-3-319-04981-6_48.

  PMID: 25366638 RESULT

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Vasospasm, Intracranial; Aneurysm

Interventions

Serum Albumin, Human

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Serum Albumin; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Blood Proteins

Limitations and Caveats

Our study has several limitations. ALISAH is an early phase design and we do not have concurrent controls. In addition, the study was neither randomized nor powered to test for efficacy effects.

Results Point of Contact

• Title: Jose I Suarez, MD, Professor of Neurology
• Organization: Baylor College of Medicine

jisuarez@bcm.edu

713-798-8472

Study Officials

• Jose I. Suarez, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: January 26, 2006
• First Posted: January 27, 2006
• Study Start: January 1, 2006
• Primary Completion: January 1, 2011
• Study Completion: April 1, 2011
• Last Updated: April 1, 2015
• Results First Posted: April 1, 2015

Record last verified: 2015-03

Locations

US (4); CA (2)