Treatment of Subarachnoid Hemorrhage With Human Albumin

Not Applicable

Terminated

Conditions: Subarachnoid Hemorrhage

Interventions: Drug: 25% human albumin

Registration Number: NCT00283400

Lead Sponsor: Baylor College of Medicine

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.

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 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 47

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
dosage tier 1	25% human albumin	0.625 g/kg 25% human albumin
dosage tier 2	25% human albumin	1.25 g/kg 25% human albumin
dosage tier 3	25% human albumin	1.875 g/kg 25% human albumin
dosage tier 4	25% human albumin	2.5 g/kg 25% human albumin

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability of the 25% Human Albumin Dosages and the Functional Outcome.	9 days after enrollment	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.

Secondary Outcome Measures

Name	Time	Method
Serious Adverse Events	within 3 months after enrollment	Serious adverse events included neurological and medical complications and neurological deterioration. Neurological deterioration was defined as a decline by more than 2 points in the Glasgow Coma Scale.
Good Clinical Outcome Was Defined as a Glasgow Outcome Scale Score of 0-1	3 months after enrollment	Number of subjects with good clinical outcome defined as a Glasgw Outcome Scale score of 0-1

Trial Locations

Locations (6): The Johns Hopkins Hospital
🇺🇸
Baltimore, Maryland, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
University of Toronto
🇨🇦
Toronto, Ontario, Canada
Penn State University
🇺🇸
Hershey, Pennsylvania, United States
University of Calgary
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Calgary, Alberta, Canada
Data Coordination Unit, Department of Biostatistics, Bioinformatics and Epidemiology, at the Medical University of South Carolina
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Charleston, South Carolina, United States