Design of a PROspective multi-national CLOTBUST collaboration on reperfusion therapies for stroke (CLOTBUST-PRO).
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.


OBJECTIVE
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.


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.
Saqqur
Maher
M
Department of Medicine (Neurology), University of Alberta, Alberta, Canada.
Tsivgoulis
Georgios
G
Molina
Carlos A
CA
Demchuk
Andrew M
AM
Garami
Zsolt
Z
Barreto
Andrew
A
Spengos
Konstantinos
K
Forteza
Alex
A
Mikulik
Robert
R
Sharma
Vijay K
VK
Brunser
Alex
A
Martinez
Patricia
P
Montaner
Joan
J
Kohrmann
Martin
M
Schellinger
Peter D
PD
Alexandrov
Andrei V
AV
D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D015337:Multicenter Studies as Topic; D011446:Prospective Studies; D015424:Reperfusion / Q000379:methods*; D012107:Research Design; D020521:Stroke / Q000628:therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator