Treatment of Subarachnoid Hemorrhage With Human Albumin

This study has been terminated.
(Study met safety endpoints)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jose I. Suarez, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00283400
First received: January 26, 2006
Last updated: March 18, 2015
Last verified: March 2015
  Purpose

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


Condition Intervention
Subarachnoid Hemorrhage
Drug: 25% human albumin

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Subarachnoid Hemorrhage With Human Albumin

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Safety and Tolerability of the 25% Human Albumin Dosages and the Functional Outcome. [ Time Frame: 9 days after enrollment ] [ Designated as safety issue: Yes ]
    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:
  • Serious Adverse Events [ Time Frame: within 3 months after enrollment ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: 3 months after enrollment ] [ Designated as safety issue: No ]
    Number of subjects with good clinical outcome defined as a Glasgw Outcome Scale score of 0-1


Enrollment: 47
Study Start Date: January 2006
Study Completion Date: April 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other Name: 25% human albumin
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.
Other Name: 25% human albumin
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.
Other Name: 25% human albumin
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.
Other Name: 25% human albumin

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.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00283400

Locations
United States, Maryland
The Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
United States, Pennsylvania
Penn State University
Hershey, Pennsylvania, United States, 17033
United States, South Carolina
Data Coordination Unit, Department of Biostatistics, Bioinformatics and Epidemiology, at the Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Canada, Alberta
University of Calgary
Calgary, Alberta, Canada
Canada, Ontario
University of Toronto
Toronto, Ontario, Canada
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Principal Investigator: Jose I. Suarez, MD Baylor College of Medicine
  More Information

Publications:

Responsible Party: Jose I. Suarez, Professor of Neurology, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00283400     History of Changes
Other Study ID Numbers: R01NS049135, R01NS049135
Study First Received: January 26, 2006
Results First Received: February 5, 2013
Last Updated: March 18, 2015
Health Authority: United States: Federal Government

Keywords provided by Baylor College of Medicine:
subarachnoid hemorrhage
SAH
human albumin
HA
cerebral vasospasm
aneurysm
neuroprotective

Additional relevant MeSH terms:
Hemorrhage
Subarachnoid Hemorrhage
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Intracranial Hemorrhages
Nervous System Diseases
Pathologic Processes
Vascular Diseases
Albunex
Contrast Media
Diagnostic Uses of Chemicals
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 01, 2015