CEREBRAL INTRAARTERIAL FIBRINOLYSIS AT THE CROSSROADS - IS A PHASE-III TRIAL ADVISABLE AT THIS TIME

PURPOSE: To describe the rationale for fibrinolysis, review the state of the art in cerebral fibrinolysis, and discuss whether it is time fo r phase III studies of cerebral intraarterial fibrinolysis. METHODS: C ritical review of the literature with statistical reevaluation of sign ificant clinical data. RESULTS: There are abundant phase III data supp orting the use of thrombolysis in the cardiovascular system. However, there are no published phase III trials of intraarterial fibrinolysis in stroke. All reports of cerebral intraarterial fibrinolysis are case series. The studies are typically small with variable treatment proto cols and designs that are susceptible to bias. The only analysis compa ring cerebral intraarterial fibrinolysis with conventional therapy is based on nonconcurrent controls. CONCLUSIONS: Stroke is common and cos tly. Acute stroke intervention with fibrinolytic drugs is theoreticall y justified. Studies done to date have significant, inferential limita tions. The data suggest an association between thrombolysis, recanaliz ation, and prognosis. However, imprecision and inadequate control of s ystematic error preclude conclusions regarding clinical outcomes. Rand omized, controlled trials are needed to establish the clinical value o f cerebral local intraarterial fibrinolysis. However, cerebral local i ntraarterial fibrinolysis availability, the cerebral local intraarteri al fibrinolysis learning curve, anticipated technological advances, un resolved procedural controversies, and ethical and fiscal consideratio ns make a large phase III trial impractical and ill-advised at the pre sent time. Additional basic research is needed to set the stage for a successful clinical trial.