Background: Patients with unwitnessed stroke represent >25% of all strokes. Clinical trials enrolling patients with unwitnessed stroke onset have conservatively used last known normal (LKN) as the time of stroke onset. We explored the impact of alternative methods of selecting onset time in unwitnessed strokes on eligibility into an acute stroke therapeutic trial using a representative sample of acute stroke subjects. Methods: We analyzed data on 641 consecutive patients with suspected stroke presenting to our hospital between January 2007 and July 2008. Time of onset was calculated by 3 methods: (1) LKN, (2) first known abnormal (FKA), and (3) midpoint between LKN and FKA. Subjects with incomplete data or a final diagnosis of nonischemic stroke were excluded. Rates of trial eligibility based on different onset times were compared for several inclusion time windows. Results: Onset time was known in 440 subjects (69%). Of the remaining 201 patients with unwitnessed onset, 114 (57%) were "wake-up" strokes. Among unwitnessed stroke subjects, eligibility increased from 18% using LKN to 57% using FKA at 4.5 hours and 42% to 81% at 9 hours (P <.001), respectively. Overall enrollment eligibility for the full cohort increased from 36% to 48% at 4.5 hours and 61% to 73% at 9 hours (P <.001), respectively. Conclusion: Given potential advantages in safety evaluation and the historical inadequate enrollment rates in acute stroke trials, alternative onset time definitions, perhaps in combination with advanced neuroimaging methods (e.g., fluid-attenuated inversion recovery-diffusion-weighted imaging mismatch), should be considered for early-phase trials.
|Original language||English (US)|
|Number of pages||3|
|Journal||Journal of Stroke and Cerebrovascular Diseases|
|State||Published - Apr 2013|
ASJC Scopus subject areas
- Clinical Neurology
- Cardiology and Cardiovascular Medicine