Published online by Cambridge University Press: 26 August 2009
The disappointingly slow progress in developing effective therapies for ischemic stroke, along with the clinical development of diffusion and perfusion MRI, has led to a re-evaluation of the strategies for the design of stroke clinical trials. Rapid, early MRI has been proposed and begun to be used in stroke trials as a means of optimizing patient selection and as a direct measure of the effect of treatments on cerebral infarction, as the marker of therapeutic response.
The need for a more rationale approach to clinical development of stroke therapeutics
The first and only success in developing an approved therapy culminated in the pivotal trials of intravenous recombinant tissue plasminogen activator (t-PA), reported in 1995 and leading to regulatory approval in 1996. The key insight of the designers of these trials was optimizing the sample with regard to time to treatment, requiring patients to be treated within three hours from onset of symptoms. They recognized that very early stroke treatment would be more effective and that the earliest cases are most likely to still have the causative arterial occlusions, which may spontaneously lyse at later times. Thus, patients were included across the broad range of clinical features, and selection of patients by imaging confirmation of the diagnosis or pathologic features most amenable to the treatment was not necessary to prove the efficacy of intravenous t-PA for the less than 3 hours' time window.