Treatment of Subarachnoid Hemorrhage With Human Albumin (ALISAH)

This study has been terminated.
(The study met the pre-specified criteria for stopping the trial)
Sponsor:
Information provided by (Responsible Party):
Jose I. Suarez, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01747408
First received: June 23, 2011
Last updated: December 10, 2012
Last verified: December 2012
  Purpose

The proposed study was set up to evaluate the tolerability and safety of 25% human albumin (HA) therapy in patients with subarachnoid hemorrhage (SAH). It is estimated that 37,500 people in the USA have SAH every year. SAH is associated with a 51% mortality rate and one third of survivors are left functionally dependent. Cerebral vasospasm (CV) has been identified as the most important reason for neurological deterioration. CV may be due to multiple molecular mechanisms. The use of a neuroprotective agent with various actions, likes HA, would be important for prevention of CV and improved clinical outcome in patients with SAH. The proposed open-label, dose-escalation study will have important public health implications by providing necessary information for a definitive phase III clinical trial regarding the efficacy of treatment with HA in patients with SAH. The study was to enroll a maximum of 80 patients with SAH who meet the eligibility criteria. Four dosages of HA (0.625, 1.25, 1.875, and 2.5 g/kg) administered daily for seven days will be evaluated. The lowest dosage was to be evaluated in the first group of 20 subjects. A specific safety threshold was defined based on data from previous studies. The Data and Safety Monitoring Board approved or disapproved advancing to the next higher HA dosage based on the evaluation of the rate of congestive heart failure (CHF). The study assessed three outcomes: safety and tolerability of the HA dosages and the functional outcome. The primary tolerability outcome was defined as the subject's ability to receive the full allocated dose of HA without incurring frank CHF that requires termination of treatment. Secondary safety outcomes were serious adverse events (including neurological and medical complications, and anaphylactic reactions). Neurological complications comprise incidence of CV, rebleeding, hydrocephalus, and seizures after treatment. The three-month functional outcome determined, by Glasgow Outcome Scale, Barthel Index, modified Rankin Scale, NIH Stroke Scale and Stroke Impact Scale was measured to obtain a preliminary estimate of the treatment effect of HA. The timeline of the study is three years.


Condition Intervention Phase
Subarachnoid Hemorrhage
Drug: Human Albumin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group 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:
  • Number of participatns with cardiovascular adverse events as a measure of safety and tolerability [ Time Frame: Up to 48 hours after treatment administration ] [ Designated as safety issue: Yes ]
    The study will investigate the number of patients experiencing moderate-to-severe acute heart failure for any given dosage tier directly related to treatment administration. Specifically, if at least 2 patients per dosage tier experience such serious event the study will be terminated.


Secondary Outcome Measures:
  • GOS [ Time Frame: 3 months after enrollment ] [ Designated as safety issue: No ]
    The study will measure the the Glasgow Outcome Scale to obtain preliminary estimates of treatment effects.

  • mRs [ Time Frame: 3 months after study enrollment ] [ Designated as safety issue: No ]
    The study will measure the the modified Rankin Scale to obtain preliminary estimates of treatment effects.

  • NIHSS [ Time Frame: 3 months after enrollment ] [ Designated as safety issue: No ]
    The study will measure the NIH Stroke Scale to obtain preliminary estimates of treatment effects.

  • SIS [ Time Frame: 3 months after enrollment ] [ Designated as safety issue: No ]
    The study will measure the Stroke Impact Scale to obtain preliminary estimates of treatment effects.


Enrollment: 47
Study Start Date: June 2006
Study Completion Date: May 2011
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 25% human albumin
Subjects will be entered into one of 4 increasing dosages of 25% human albumin sequentially. Once the first 20 subjects have been enrolled and the DSMB reviews data and approves moving to the next dosage tier patients will be entered into the following dosage tier.
Drug: Human Albumin

25% human albumin given in four escalating doses:

  1. Group 1: .625g/kg infused over 3hrs daily X 7day
  2. Group 2: 1.25g/kg infused over 3hrs daily X 7day
  3. Group 3: 1.875g/kg infused over 3hrs daily X 7day
  4. Group 4: 2.5g/kg infused over 3hrs daily X 7day
Other Name: Albumin

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
    • Head computed tomography demonstrates subarachnoid hemorrhage (rating scale 2-4).
    • 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 treatment initiation but within 72 hours of symptom onset. Accepted treatments of aneurysms include surgical clipping or endovascular embolization.
    • Signed and dated informed written consent by the subject or his/her legally authorized representative.

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
  • Head computed tomography rating scale of 0 - 1
  • History within the past 6 months, and/or physical findings on admission of decompensated heart failure (NYHA Class III and IV or 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 > or = 40% (if available).
  • Serum creatinine > 2.0 mg/dl or creatinine clearance < 50 ml/min.
  • Pregnancy, lactation or parturition within previous 30 days.
  • Known allergy to albumin.
  • Severe prior physical disability (Rankin Scale > 2) that precludes evaluation of clinical outcome measures.
  • History of severe chronic obstructive lung disease (FEV1 < 50% predicted, increased shortness of breath, and repeated exacerbations which have an impact on patients' quality of life).
  • History of confirmed or suspected liver failure (increased prothrombin time, elevated liver enzymes, hypoalbuminemia, and hyperbilirrubinemia with or without peripheral edema and encephalopathy)
  • 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: NCT01747408

Locations
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Study Chair: Jose I Suarez, MD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Jose I. Suarez, Professor of Neurology, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01747408     History of Changes
Other Study ID Numbers: H-21012
Study First Received: June 23, 2011
Last Updated: December 10, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
subarachnoid hemorrhage

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

ClinicalTrials.gov processed this record on July 31, 2014