Treatment of Subarachnoid Hemorrhage With Human Albumin

NCT ID: NCT00283400

Last Updated: 2015-04-01

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-01-31

Study Completion Date

2011-04-30

Brief Summary

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

Detailed Description

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An estimated 37,500 people in the United States have subarachnoid hemorrhage (SAH) every year. SAH is usually secondary to a brain aneurysm that has burst. In SAH the bleeding accumulates around the lining of the brain. SAH is associated with a 51percent mortality rate, and one third of survivors are left functionally dependent. Cerebral vasospasm, which is a delayed narrowing of the cerebral arteries following SAH, has been identified as the most important reason for neurological deterioration and bad outcome in cases of SAH. Cerebral vasospasm may be caused by multiple mechanisms.

Treatment with a neuroprotective agent, such as human albumin (HA), may be beneficial for prevention of cerebral vasospasm and improved clinical outcome in patients with SAH. HA is a major protein found in blood and is responsible for maintaining fluid balance in the vascular system (blood vessels). The purpose of this study was to determine the safety and tolerability of 25 percent HA therapy in patients with SAH. This open-label, dose-escalation study will provide necessary information for a future definitive phase III clinical trial on the efficacy of treatment with HA in patients with SAH.

The study was designed to enroll 80 patients at 5 centers in the US. Patients with eligible SAH first underwent surgical or endovascular repair, which was considered standard care. Endovascular repair was a repair of the aneurysm from the inside of the blood vessel.

Following neurosurgical or endovascular treatment, participants were given a daily infusion of HA for 7 days. The HA dose was allocated as follows: the first tier (20 patients) would receive 0.625 grams (g) of HA per kilogram (kg) of body weight; patients in the second tier would receive 1.25g of HA per kg; patients in the third tier would receive 1.875g of HA per kg; and patients in the fourth tier would receive 2.5g of HA per kg. Safety and tolerability was evaluated by the Data and Safety Monitoring Board (DSMB) after each tier was completed and before the study advanced to the next dose tier. A specific safety threshold for congestive heart failure and other adverse events was defined based on data from previous studies.

In the follow-up phase, patients participated in study-related evaluations of their health at 15 days and three months. Duration of the study for participants was 90 days.

Conditions

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Subarachnoid Hemorrhage

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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dosage tier 1

0.625 g/kg 25% human albumin

Group Type ACTIVE_COMPARATOR

25% human albumin

Intervention Type 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 2

1.25 g/kg 25% human albumin

Group Type ACTIVE_COMPARATOR

25% human albumin

Intervention Type 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 3

1.875 g/kg 25% human albumin

Group Type ACTIVE_COMPARATOR

25% human albumin

Intervention Type 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 4

2.5 g/kg 25% human albumin

Group Type ACTIVE_COMPARATOR

25% human albumin

Intervention Type DRUG

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

Interventions

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25% human albumin

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
* History of chronic lung disease
* Current participation in another drug treatment protocol.
* Severe terminal disease with life expectancy less than 6 months.
Minimum Eligible Age

18 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Jose I. Suarez

Professor of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jose I. Suarez, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

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The Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Penn State University

Hershey, Pennsylvania, United States

Site Status

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

Charleston, South Carolina, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

University of Calgary

Calgary, Alberta, Canada

Site Status

University of Toronto

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type BACKGROUND
PMID: 15070109 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12072693 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10657410 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8450326 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11487482 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15163774 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11157196 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12063314 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12176131 (View on PubMed)

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.

Reference Type RESULT
PMID: 22267829 (View on PubMed)

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.

Reference Type RESULT
PMID: 25366638 (View on PubMed)

Other Identifiers

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R01NS049135

Identifier Type: NIH

Identifier Source: secondary_id

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R01NS049135

Identifier Type: NIH

Identifier Source: org_study_id

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