Treatment of Subarachnoid Hemorrhage With Human Albumin

Terminated

Phase N/A Results

Trial Description

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.

Trial Stopped: Study met safety endpoints

Conditions

Interventions

  • human serum albumin (albumin)Drug
    Intervention Desc: given to replace lost albumin to maintain proper body fluid distribution
  • Human albumin Drug
    Intervention Desc: after approval by the Data and Safety Monitoring Board dosage tier will be escalated to the subsequent higher level sequentially.
    ARM 1: Kind: Experimental
    Label: dosage tier 1
    Description: 0.625 g/kg
    ARM 2: Kind: Experimental
    Label: dosage tier 2
    Description: 1.25 g/kg
    ARM 3: Kind: Experimental
    Label: dosage tier 3
    Description: 1.875 g/kg
    ARM 4: Kind: Experimental
    Label: dosage tier 4
    Description: 2.5 g/kg
  • 25% human albumin Drug
    Other Names: 25% human albumin
    Intervention Desc: 25% human albumin: after approval by the Data and Safety Monitoring Board dosage tier would be escalated to the subsequent higher level sequentially.
    ARM 1: Kind: Experimental
    Label: dosage tier 1
    Description: 0.625 g/kg 25% human albumin
    ARM 2: Kind: Experimental
    Label: dosage tier 2
    Description: 1.25 g/kg 25% human albumin
    ARM 3: Kind: Experimental
    Label: dosage tier 3
    Description: 1.875 g/kg 25% human albumin
    ARM 4: Kind: Experimental
    Label: dosage tier 4
    Description: 2.5 g/kg 25% human albumin

Trial Design

  • Allocation: Non-Randomized
  • Masking: Open Label
  • Purpose: Treatment
  • Intervention: Parallel Assignment

Patient Involvement

Patients with eligible SAH will first undergo surgical or endovascular repair, which is considered standard care. 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.

Outcomes

Type Measure Time Frame Safety Issue
Primary 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 Serious adverse events (including neurological and medical complications) and neurological deterioration.
Primary 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 15 days after enrollment Yes
Primary Safety and Tolerability of the 25% Human Albumin Dosages and the Functional Outcome. 9 days after enrollment Yes
Secondary Serious Adverse Events within 3 months after enrollment Yes
Secondary Good Clinical Outcome Was Defined as a Glasgow Outcome Scale Score of 0-1 3 months after enrollment No

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