- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00968227
Effect of Red Blood Cell Transfusion on Brain Metabolism in Patients With Subarachnoid Hemorrhage
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Missouri
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St Louis, Missouri, United States, 63110
- Washington University Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Aneurysmal SAH confirmed by angiography
- Hemoglobin < 12.5 gm/dl
One of the following:
- Considered at increased risk for vasospasm by care team
- Angiographic vasospasm
- Delayed ischemic deficit
- Able to be studied within 2 weeks after subarachnoid hemorrhage
Exclusion Criteria:
- Active Coronary Artery Disease
- Severe congestive heart failure
- Jehovah's witness
- Unable to obtain appropriately matched blood
- Other contraindications for transfusion
- Pregnancy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Transfusion
|
Transfusion of 1 unit of packed red blood cells over 1 hour.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Oxygen Delivery in Vulnerable Brain Regions
Time Frame: 1 hour
|
Change in oxygen delivery after transfusion in brain regions with low baseline delivery.
|
1 hour
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Oxygen Extraction Fraction in Regions With Low Baseline Delivery.
Time Frame: 1 hour
|
Change in oxygen extraction fraction after transfusion of 1 unit of RBC in regions with low baseline delivery (DO2 < 4.5 ml/100g/min.
|
1 hour
|
Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 07-0733
- NIH 5P50NS035966-10
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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