Grants and Contracts Details
Description
Head injury is a complex disease involving two distinct patterns of injury, primary injury and secondary
injury. There is significant morbidity and mortality associated with brain injury with about 50,000 deaths and
235,000 hospitalizations each year. In spite of major advancements in the understanding of the molecular
mechanisms associated with secondary injury induced by traumatic brain injury (TBl), failure to discover a
therapeutic agent to mitigate these affects in humans has been a persistent disappointment to researchers.
Several agents have shown promise in the laboratory but have not translated into success beyond the animal
model. When trials were comprehensively reviewed, inadequate statistical sensitivity, inadequate pre-clinical
data and lack of drug disposition data documenting access to the brain were identified as important
contributing factors.
Cyclosporine A (CsA) has been shown in multiple animal models to be neuroprotective by attenuating
mitochondrial dysfunction and preventing axonal destruction thus improving outcomes. Animal studies have
shown that a continuous infusion preceded by a bolus dose given within 12 hours of injury maximizes CsA
protective effects. In addition, our early clinical trial investigations of CsA in severe TBI have shown that the
drug is safe, that higher continuous infusion doses are more effective, that CsA is detected in the central
nervous system, and that CsAtreated patients have a trend toward better outcomes.
This planning grant proposal is necessary to complete the steps required for the initiation of a Phase III
multi-center clinical trial in severe TEl patients evaluating CsA therapy (CASTBl). A double-blind, placebo
controlled trial of 1218 patients investigating CsA will be designed to test the hypothesis that patients suffering
from a severe TEl treated with a continuous infusion of CsA for three days will have an improved functional
outcome compared to placebo. The primary endpoint assessment of functional outcome will be the Glasgow
Outcome Scale at 6 months.
This planning grant period will be used to: (1) identify executive committee and sub-committee members;
(2) finalize study documents including protocol, manual of operations, case report forms, and investigational
new drug application; (3) recruit study sites; (4) prepare and validate the data management systems; (5)
develop training and certification materials for outcome assessments; (6) organize investigator's meeting; and
(7) prepare Phase III CASTEl grant for submission.
Status | Finished |
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Effective start/end date | 1/1/08 → 12/31/08 |
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