Albumin for Intracerebral Hemorrhage Intervention - Full Text View

Sponsor:	Georgetown University
Collaborator:	Baxter Healthcare Corporation
Information provided by:	Georgetown University
ClinicalTrials.gov Identifier:	NCT00990509

Purpose

The purpose of this study is to find out what effects, good and bad, the medication Albumin has on subjects who have experienced a type of stroke known as an intracerebral hemorrhage (ICH). An ICH is when spontaneous bleeding into the brain occurs due to fragile blood vessels.

This research is being done because currently there is no effective treatment for ICH. However, study investigators believe that Albumin, the medication being tested in this study, is safe and may help improve patient recovery from ICH over time.

Subjects will be enrolled in the study for a total of 90 days. Following enrollment, subjects will be randomized to receive 3 daily injections of either Albumin or Placebo (liquid with no drug), and will receive 3 brain MRI scans (with and without contrast), as described below.

All subjects will be monitored continuously through 96 hours after enrollment (5 days) in the Georgetown ICU. Blood tests and clinical evaluations of neurological status, consisting of questions about subjects' functional abilities and medical history, will occur in the Georgetown ICU once every 24 hours through post-enrollment Day 5. Additionally, subjects will receive daily chest x-rays, and daily EKGs (exams that monitor how your heart is doing by placing electrodes, or small monitors, on your skin in specific locations).

Similar clinical evaluations will occur at Day 30 and Day 90. Should subjects be discharged at these time points, day 30 assessments will occur over the phone, and day 90 assessments will occur in-person at Georgetown University Medical Center.

Condition	Intervention	Phase
Intracerebral Hemorrhage	Drug: Albumin Drug: Placebo Procedure: Brain MRI with and without contrast	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Albumin for Intracerebral Hemorrhage Intervention

Resource links provided by NLM:

MedlinePlus related topics: X-Rays

U.S. FDA Resources

Further study details as provided by Georgetown University:

Primary Outcome Measures:

Frequency and severity of blood brain barrier disruption. HARM is assessed on the post-contrast study using a previously developed 5 point scale. [ Time Frame: Day 5 MRI ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Assessment of safety of albumin administration in primary ICH (frank pulmonary edema as visualized on chest X-Ray, congestive heart failure, neurological deterioration [4-pt worsening on NIHSS]) [ Time Frame: Through Day 90 following enrollment ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	September 2009
Estimated Study Completion Date:	September 2012
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Albumin: Experimental	Drug: Albumin Three (3) daily IV infusions of 1.25 g/kg Albumin (25%) on Days 1-3 following enrollment. Procedure: Brain MRI with and without contrast All subjects will receive 3 brain MRI studies, regardless of if they are randomized into Albumin or Placebo condition. MRIs will be with and without contrast will be performed at: Baseline 48 hours after enrollment(approximately Day 3) 96 hours after drug treatment begins (approximately Day 5)
Placebo: Placebo Comparator	Drug: Placebo Three (3) daily IV infusions of 1.25 g/kg Saline solution on Days 1-3 following enrollment Procedure: Brain MRI with and without contrast All subjects will receive 3 brain MRI studies, regardless of if they are randomized into Albumin or Placebo condition. MRIs will be with and without contrast will be performed at: Baseline 48 hours after enrollment(approximately Day 3) 96 hours after drug treatment begins (approximately Day 5)

Arms

Assigned Interventions

Albumin: Experimental

Drug: Albumin

Three (3) daily IV infusions of 1.25 g/kg Albumin (25%) on Days 1-3 following enrollment.

Procedure: Brain MRI with and without contrast

All subjects will receive 3 brain MRI studies, regardless of if they are randomized into Albumin or Placebo condition.

MRIs will be with and without contrast will be performed at:

Baseline
48 hours after enrollment(approximately Day 3)
96 hours after drug treatment begins (approximately Day 5)

Placebo: Placebo Comparator

Drug: Placebo

Three (3) daily IV infusions of 1.25 g/kg Saline solution on Days 1-3 following enrollment

Procedure: Brain MRI with and without contrast

All subjects will receive 3 brain MRI studies, regardless of if they are randomized into Albumin or Placebo condition.

MRIs will be with and without contrast will be performed at:

Baseline
48 hours after enrollment(approximately Day 3)
96 hours after drug treatment begins (approximately Day 5)

Detailed Description:

We aim to determine the safety and explore the efficacy of human albumin as a neuroprotective (or cytoprotective) agent for the treatment of acute primary supratentorial ICH. Albumin therapy has been shown to be cytoprotective in animal studies of both ischemic stroke and intracerebral hemorrhage, and in a phase II human study in ischemic stroke.

To date no acute intervention (beyond supportive medical care) has been identified to improve outcomes in patients with primary ICH. Neuronal injury from a primary ICH is due not only to the space occupying effects of the hemorrhage but also due to the development of edema and toxicity from blood breakdown products in the subacute phase. Cytoprotective strategies targeted to limit blood brain barrier (BBB) breakdown and edema formation hold promise as treatment strategies to limit this injury.

A number of MR imaging outcome markers demonstrating a potential neuroprotective effect include measures of hematoma volume, perihematomal edema, and blood brain barrier disruption. The term "hyperintense acute injury marker" (HARM) has been proposed to describe the radiologic finding of hyperintense signal within the cerebrospinal fluid spaces visualized on post-contrast fluid attenuated inversion recovery (FLAIR) MRI in patients with acute ischemic stroke. HARM has the potential to serve as a marker of blood brain barrier disruption in patients with primary ICH. The current study will involve serial MR imaging in ICH patients randomized to placebo vs. albumin to assess whether there are differences in the frequency of HARM and perihematomal edema in the albumin treated patients.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Primary supratentorial ICH
< 24 hours from symptom onset
Age >18
Signed informed consent obtained from the patient or patient's legally authorized representative

Exclusion Criteria:

ICH volume < 10 cc
Glasgow Coma Scale < 8
Surgical evacuation anticipated
Pre-existing medical, neurological or psychiatric disease that would confound the neurological, functional, or imaging evaluations
Pregnancy or breastfeeding
Hemodynamic instability (SBP < 100 mmHg, > 200 mmHg)
Current participation in another experimental treatment protocol
Renal impairment with GFR < 30 or Creatinine > 2.0
History of or known allergy to albumin
History of or known severe allergy to rubber latex
Episode/exacerbation of congestive heart failure (CHF) from any cause in the last 6 months. (An episode of congestive heart failure is any heart failure that required a change in medication, diet or hospitalization)
Acute myocardial infarction in the last 6 months
Elevated serum troponin level on admission > 0.1 mcg/L
Known valvular heart disease with CHF in the last 6 months
Known (or in the investigator's judgment) existence of severe aortic stenosis or mitral stenosis
Cardiac surgery involving thoracotomy (e.g., coronary artery bypass graft (CABG), valve replacement surgery) in the last 6 months
Suspicion of aortic dissection on admission
Acute arrhythmia (including any tachy- or bradycardia) with hemodynamic instability on admission (systolic blood pressure < 100 mmHg)
Findings on physical examination of any of the following:
1. jugular venous distention (JVP > 4 cm above the sternal angle)
2. 3rd heart sound
3. resting tachycardia (heart rate > 100/min) attributable to congestive heart failure
4. abnormal hepatojugular reflux
5. lower extremity pitting edema attributable to congestive heart failure or without apparent cause
6. bilateral rales and/or
7. if a chest x-ray is performed, definite evidence of pulmonary edema, bilateral pleural effusion, or pulmonary vascular redistribution.
Current acute or chronic lung disease requiring supplemental chronic or intermittent oxygen therapy.
Prosthetic heart valves
Contraindication to MRI (metal implant, etc.)
Patients on ventilators at the time of enrollment
Documented left ventricular ejection fraction < 35%

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00990509

Contacts

Contact: Shoshana Goldberg, BA	202-687-7288	sg434@georgetown.edu
Contact: Chelsea Kidwell, MD	202-687-7302	ck256@georgetown.edu

Locations

United States, District of Columbia
Georgetown University Hospital	Recruiting
Washington, District of Columbia, United States, 20007
Contact: Chelsea Kidwell, MD 202-687-7302 ck256@georgetown.edu
Principal Investigator: Chelsea Kidwell, MD
Sub-Investigator: Ravi Menon, MD
Sub-Investigator: Richard Burgess, MD, PhD

Sponsors and Collaborators

Georgetown University

Baxter Healthcare Corporation

Investigators

Principal Investigator:

Chelsea Kidwell, MD

Georgetown University

More Information

No publications provided

Responsible Party:	Georgetown University ( Chelsea Kidwell, MD Professor of Neurology; Medical Director, Georgetown University Stroke Center )
Study ID Numbers:	2009-173
Study First Received:	October 1, 2009
Last Updated:	December 8, 2009
ClinicalTrials.gov Identifier:	NCT00990509 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Georgetown University:

Primary ICH
Albumin
MRI
Neuroimaging outcome
Placebo-controlled
Phase II

Blinded
Safety
Acute ICH
ICH
Primary acute (< 24hours) supratentorial ICH

Additional relevant MeSH terms:

Cerebral Hemorrhage
Pathologic Processes
Nervous System Diseases
Vascular Diseases
Central Nervous System Diseases

Cardiovascular Diseases
Intracranial Hemorrhages
Brain Diseases
Hemorrhage
Cerebrovascular Disorders

ClinicalTrials.gov processed this record on February 08, 2010