Background The benefit of intravenous (i.v.) tissue plasminogen
activator (tPA) in acute ischemic stroke (IS) is attributable to lysis
of thrombus and restoration of perfusion to ischemic but not yet
infarcted brain.
Aims Our multicentre collaborative group prospectively implemented a
protocol for transcranial Doppler assessment of intracranial
recanalization with tPA treatment based on the CLOTBUST clinical trial
(CLOTBUST-PRO). We aim to determine whether early recanalization (within
1 h from tPA bolus) is independently associated with better 3-month
outcome in patients with intracranial arterial occlusions and correlates
to a shorter time interval elapsed from symptom onset to tPA bolus.
Subjects and methods Consecutive patients with acute IS due to
intracranial arterial occlusions will be treated with standard i.v.-tPA
and continuously monitored with 2 MHz Transcranial Doppler for arterial
recanalization. Early recanalization will be determined with the
previously validated Thrombolysis in Brain Ischemia flow-grading system
within 60 min after tPA bolus. Power calculations are based on the
assumption of alpha=0.05 (two-sided test) and probabilities of
functional independence at 3 months of 0.50 and 0.35 in patients with
early complete recanalization and persisting occlusion, respectively.
Detection of a 15% difference with a power of 0.824 requires an
estimated sample of 480 patients of whom 25% are expected to achieve
early recanalization while 75% will have persisting occlusion at 1 h
after tPA bolus. We also plan to test prespecified secondary hypotheses
within the projected study sample.
Conclusions CLOTBUST-PRO is designed to determine if the timing (within
1 h from tPA bolus) of tPA-induced arterial recanalization is an
independent determinant of 3-month functional recovery. We also seek to
demonstrate that the sooner the tPA is given to stroke patients, the
earlier the recanalization occurs and the greater is the likelihood of
functional independence at 3 months
