Treatment of Subarachnoid Hemorrhage With Human Albumin

Condition(s) targeted: Subarachnoid Hemorrhage

Intervention: human albumin (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: Baylor College of Medicine

Official(s) and/or principal investigator(s):
Jose I. Suarez, MD, Principal Investigator, Affiliation: Baylor College of Medicine

Overall contact:
Jose I. Suarez, MD, Phone: 713-798-8472, Email: jisuarez@bcm.tmc.edu

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

Official title: Treatment of Subarachnoid Hemorrhage With Human Albumin

Study design: Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Safety and tolerability of the 25% HA dosages and the functional outcome. Tolerability outcome: Subject's ability to receive the full allocated HA dose without incurring frank congestive heart failure or experiencing anaphylactic reactions that require

Secondary outcome: Serious adverse events (including neurological and medical complications) and neurological deterioration.

Detailed description: 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 is 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 will enroll 80 patients at 5 centers in the US. Patients with eligible SAH will first undergo surgical or endovascular repair, which is considered standard care. Endovascular repair is a repair of the aneurysm from the inside of the blood vessel.

Following neurosurgical or endovascular treatment, participants will be given a daily infusion of HA for 7 days. The HA dose will be allocated as follows: the first tier (20 patients) will receive 0. 625 grams (g) of HA per kilogram (kg) of body weight; patients in the second tier will receive 1. 25g of HA per kg; patients in the third tier will receive 1. 875g of HA per kg; and patients in the fourth tier will receive 2. 5g of HA per kg. Safety and tolerability will be evaluated by the Data and Safety Monitoring Board (DSMB) after each tier is completed and before the study advances to the next dose tier. A specific safety threshold for congestive heart failure and other adverse events has been defined based on data from previous studies.

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

Minimum age: 18 Years. Maximum age: 79 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients (male or female) must be 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 demonstrates subarachnoid hemorrhage.

- Cerebral angiography reveals the presence of saccular aneurysm(s) in a location that

explains the subarachnoid hemorrhage.

- Treatment of cerebral aneurysm must be 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 cannot 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 has 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.

Jose I. Suarez, MD, Phone: 713-798-8472, Email: jisuarez@bcm.tmc.edu

University of Calgary, Calgary, Alberta, Canada; Recruiting

The Johns Hopkins Hospital, Baltimore, Maryland 21287, United States; Recruiting

University of Toronto, Toronto, Ontario, Canada; Recruiting

Penn State University, Hershey, Pennsylvania 17033, United States; Recruiting

Data Coordination Unit, Department of Biostatistics, Bioinformatics and Epidemiology, at the Medical University of South Carolina, Charleston, South Carolina 29425, United States; Recruiting

Baylor College of Medicine, Houston, Texas, United States; Recruiting

Related publications:

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.

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.

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.

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.

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.

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.

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.

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.

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.

Starting date: January 2006
Last updated: March 18, 2010