Treatment of Subarachnoid Hemorrhage With Human Albumin

March 18, 2015 updated by: Jose I. Suarez, Baylor College of Medicine
The purpose of this study is to evaluate the tolerability and safety of 25 percent human albumin therapy in patients with subarachnoid hemorrhage.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

47

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada
        • University of Calgary
    • Ontario
      • Toronto, Ontario, Canada
        • University of Toronto
  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • The Johns Hopkins Hospital
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State University
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Data Coordination Unit, Department of Biostatistics, Bioinformatics and Epidemiology, at the Medical University of South Carolina
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: dosage tier 1
0.625 g/kg 25% human albumin
Drug: 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.
Active Comparator: dosage tier 2
1.25 g/kg 25% human albumin
Drug: 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.
Active Comparator: dosage tier 3
1.875 g/kg 25% human albumin
Drug: 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.
Active Comparator: dosage tier 4
2.5 g/kg 25% human albumin
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Tolerability of the 25% Human Albumin Dosages and the Functional Outcome.
Time Frame: 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.
9 days after enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serious Adverse Events
Time Frame: 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.
within 3 months after enrollment
Good Clinical Outcome Was Defined as a Glasgow Outcome Scale Score of 0-1
Time Frame: 3 months after enrollment
Number of subjects with good clinical outcome defined as a Glasgw Outcome Scale score of 0-1
3 months after enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Baylor College of Medicine

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

  • Principal Investigator: Jose I. Suarez, MD, Baylor College of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Primary Completion (Actual)

January 1, 2011

Study Completion (Actual)

April 1, 2011

Study Registration Dates

First Submitted

January 26, 2006

First Submitted That Met QC Criteria

January 26, 2006

First Posted (Estimate)

January 27, 2006

Study Record Updates

Last Update Posted (Estimate)

April 1, 2015

Last Update Submitted That Met QC Criteria

March 18, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R01NS049135 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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