Effect of Red Blood Cell Transfusion on Brain Metabolism in Patients With Subarachnoid Hemorrhage

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Washington University School of Medicine
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00968227
First received: August 26, 2009
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to determine if giving blood transfusions to anemic patients with subarachnoid hemorrhage will reduce their chances of having a stroke from vasospasm.


Condition Intervention Phase
Subarachnoid Hemorrhage
Vasospasm
Biological: Red blood cell transfusion
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Red Blood Cell Transfusion on Brain Metabolism in Patients With Subarachnoid Hemorrhage

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Percent of brain regions with low oxygen delivery before and after transfusion [ Time Frame: 1 hour ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Relationship between change in oxygen delivery and angiographic vasospasm [ Time Frame: 1 hour ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: November 2007
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Transfusion Biological: Red blood cell transfusion
Transfusion of 1 unit of packed red blood cells over 1 hour.

Detailed Description:

Each year, approximately 30,000 people suffer aneurysmal subarachnoid hemorrhage (SAH) in the United States. The most common and potentially treatable cause of secondary neurological injury in this population is delayed ischemic deficit (DID). As the name implies, this phenomenon is fundamentally a reduction of cerebral blood flow (CBF) and oxygen delivery below critical ischemic thresholds, occurring days after the onset of hemorrhage. Three inter-related physiological processes appear to be involved in the reduced oxygen delivery: severe narrowing of intracranial arteries (arterial vasospasm), intravascular volume depletion and a loss of normal autoregulatory function in the distal circulation. DID occurs in up to 40% of patients surviving SAH. One third of these patients will die from this phenomenon and another third will be left with permanent and severe disability.

The optimal treatment of vasospasm is not known. Medical management involves a number of hemodynamic manipulations and is usually referred to as hypervolemic, hypertensive, hemodilution (or Triple-H) therapy. Our knowledge of the physiological impact of the individual components or a combination of them is limited and clinical efficacy has not been established. The information gained in this study has great potential to advance our knowledge regarding the role of hematocrit in the optimal treatment of this often-devastating condition.

Changes in hematocrit can potentially impact brain oxygen delivery in two ways. First, there is a linear relationship between hemoglobin and arterial oxygen content, lower hematocrit less oxygen. Thus at a given CBF lowering hematocrit reduces brain oxygen delivery. Fortunately, the brain responds to this by increasing blood flow to restore oxygen delivery to baseline levels. Additionally, lowering hematocrit has another effect, it reduces viscosity which in and of itself can raise CBF, but in a non-linear way. It is the relative contribution of these two effects that will determine if oxygen delivery improves.

It has been proposed by largely on theoretical consideration that the "optimal" hematocrit that achieves this balance is 30-35%. Yet no study to date has assessed the relationship between hematocrit and oxygen delivery in SAH patients. Other observations, however, suggest that higher hemoglobin levels in SAH patients was associated with better outcomes. Finally another retrospective review suggested that receiving transfusions increased risk for vasospasm and poor outcome after subarachnoid hemorrhage.

We are proposing to begin a series of studies to determine the appropriate management of hematocrit in SAH patients. The first is to define the appropriate physiologic response (cerebral oxygen delivery and metabolism) to a change in hematocrit. Then the "optimal" hematocrit can be defined. Only then will we be able to properly design clinical outcome trials.

  Eligibility

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

Inclusion Criteria:

  1. Aneurysmal SAH confirmed by angiography
  2. Hemoglobin < 12.5 gm/dl
  3. One of the following:

    • Considered at increased risk for vasospasm by care team
    • Angiographic vasospasm
    • Delayed ischemic deficit
  4. Able to be studied within 2 weeks after subarachnoid hemorrhage

Exclusion Criteria:

  1. Active Coronary Artery Disease
  2. Severe congestive heart failure
  3. Jehovah's witness
  4. Unable to obtain appropriately matched blood
  5. Other contraindications for transfusion
  6. Pregnancy
  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: NCT00968227

Contacts
Contact: Michelle Allen, RN 314-747-8882 allenm@neuro.wustl.edu

Locations
United States, Missouri
Washington University Medical Center Recruiting
St Louis, Missouri, United States, 63110
Contact: Abbie Bradely, RN       BradleyA@nsurg.wustl.edu   
Principal Investigator: Michael Diringer, MD         
Principal Investigator: Raj Dhar, MD         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Michael Diringer, MD Washington University Early Recognition Center
  More Information

Publications:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00968227     History of Changes
Other Study ID Numbers: 07-0733, NIH 5P50NS035966-10
Study First Received: August 26, 2009
Last Updated: May 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
subarachnoid hemorrhage
vasospasm
transfusion
cerebral oxygen delivery
hemoglobin

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

ClinicalTrials.gov processed this record on July 26, 2014