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

Maher Saqqur, Georgios Tsivgoulis, Carlos A. Molina, Andrew M. Demchuk, Zsolt Garami, Andrew Barreto, Konstantinos Spengos, Alex Forteza, Robert Mikulik, Vijay K. Sharma, Alex Brunser, Patricia Martinez, Joan Montaner, Martin Kohrmann, Peter D. Schellinger, Andrei Alexandrov

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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 1h 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 2MHz Transcranial Doppler for arterial recanalization. Early recanalization will be determined with the previously validated Thrombolysis in Brain Ischemia flow-grading system within 60min after tPA bolus. Power calculations are based on the assumption of α=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 1h 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 1h 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.

Original languageEnglish (US)
Pages (from-to)66-72
Number of pages7
JournalInternational Journal of Stroke
Volume3
Issue number1
DOIs
StatePublished - Feb 1 2008

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Tissue Plasminogen Activator
Reperfusion
Stroke
Therapeutics
Brain Ischemia
Thrombosis
Perfusion
Clinical Trials
Brain

All Science Journal Classification (ASJC) codes

  • Neurology

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Design of a PROspective multi-national CLOTBUST collaboration on reperfusion therapies for stroke (CLOTBUST-PRO). / Saqqur, Maher; Tsivgoulis, Georgios; Molina, Carlos A.; Demchuk, Andrew M.; Garami, Zsolt; Barreto, Andrew; Spengos, Konstantinos; Forteza, Alex; Mikulik, Robert; Sharma, Vijay K.; Brunser, Alex; Martinez, Patricia; Montaner, Joan; Kohrmann, Martin; Schellinger, Peter D.; Alexandrov, Andrei.

In: International Journal of Stroke, Vol. 3, No. 1, 01.02.2008, p. 66-72.

Research output: Contribution to journalArticle

Saqqur, M, Tsivgoulis, G, Molina, CA, Demchuk, AM, Garami, Z, Barreto, A, Spengos, K, Forteza, A, Mikulik, R, Sharma, VK, Brunser, A, Martinez, P, Montaner, J, Kohrmann, M, Schellinger, PD & Alexandrov, A 2008, 'Design of a PROspective multi-national CLOTBUST collaboration on reperfusion therapies for stroke (CLOTBUST-PRO)', International Journal of Stroke, vol. 3, no. 1, pp. 66-72. https://doi.org/10.1111/j.1747-4949.2008.00167.x
Saqqur, Maher ; Tsivgoulis, Georgios ; Molina, Carlos A. ; Demchuk, Andrew M. ; Garami, Zsolt ; Barreto, Andrew ; Spengos, Konstantinos ; Forteza, Alex ; Mikulik, Robert ; Sharma, Vijay K. ; Brunser, Alex ; Martinez, Patricia ; Montaner, Joan ; Kohrmann, Martin ; Schellinger, Peter D. ; Alexandrov, Andrei. / Design of a PROspective multi-national CLOTBUST collaboration on reperfusion therapies for stroke (CLOTBUST-PRO). In: International Journal of Stroke. 2008 ; Vol. 3, No. 1. pp. 66-72.
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abstract = "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 1h 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 2MHz Transcranial Doppler for arterial recanalization. Early recanalization will be determined with the previously validated Thrombolysis in Brain Ischemia flow-grading system within 60min after tPA bolus. Power calculations are based on the assumption of α=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 1h 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 1h 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.",
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T1 - Design of a PROspective multi-national CLOTBUST collaboration on reperfusion therapies for stroke (CLOTBUST-PRO)

AU - Saqqur, Maher

AU - Tsivgoulis, Georgios

AU - Molina, Carlos A.

AU - Demchuk, Andrew M.

AU - Garami, Zsolt

AU - Barreto, Andrew

AU - Spengos, Konstantinos

AU - Forteza, Alex

AU - Mikulik, Robert

AU - Sharma, Vijay K.

AU - Brunser, Alex

AU - Martinez, Patricia

AU - Montaner, Joan

AU - Kohrmann, Martin

AU - Schellinger, Peter D.

AU - Alexandrov, Andrei

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N2 - 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 1h 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 2MHz Transcranial Doppler for arterial recanalization. Early recanalization will be determined with the previously validated Thrombolysis in Brain Ischemia flow-grading system within 60min after tPA bolus. Power calculations are based on the assumption of α=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 1h 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 1h 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.

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