Page 12 - BH-3-3

Brain & Heart Advances in stroke treatment

Table 2. Main published trials on the use of recombinant pro‑urokinase (rhPro‑UK) in AIS
Trial name No. of Design Population Efficacy Safety Results
patients outcomes outcomes
randomized
PROACT I (1998) 46 Phase II, randomized, MCA occlusion, Improved sICHm mortality Efficacy in
double-blind, multicenter intra-arterial Pro-UK recanalization, recanalization,
versus standard therapy mRS at 90 days but concerns over
hemorrhage rates
limited its adoption
PROACT II (1999) 180 Phase III, randomized, MCA occlusion within Improved sICH, mortality Improved outcomes
open-label, multicenter 6 h of symptom onset, IA recanalization, at 90 days with higher
r-proUK (9 mg)+heparin mRS at 90 days recanalization rates,
versus heparin alone but increased risk of
sICH
PROST-2 (2023) 1552 Phase III, open-label, AIS within 4.5 h Non-inferiority to sICH, mortality Non-inferiority of
non-inferiority, of symptom onset, ALT in functional rhPro-UK versus
randomized controlled ineligible for or refused outcomes at 90 ALT with a lower rate
trial EVT; IV rhPro-UK days of sICH and major
(15 mg bolus+20 mg bleeding
infusion) versus IV ALT
(0.9 mg/kg)
PUMICE (2024) 1446 Phase III, multicenter, AIS with NIHSS ≤5 Non-inferiority to sICH, mortality Completed, not
randomized, open-label, within 4.5 h of symptom ALT in functional published
blinded-endpoint onset, IV rhPro-UK outcomes at
controlled trial (35 mg) versus standard 90 days
medical treatment
Abbreviations: AIS: Acute ischemic stroke; ALT: Alteplase; MCA: Middle cerebral artery; mRS: Modified Rankin scale; NIHSS: National Institutes of
Health Stroke Scale; PROACT: Prolyse in Acute Cerebral Thromboembolism; rhPro-UK: Recombinant pro-urokinase; sICH: Symptomatic intracranial
hemorrhage.

variability in specialist opinions and practices in BAO extensive bilateral brainstem ischemia. However, this
management, reflecting a lack of consensus. evidence is classified as low quality due to limitations in
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In recent years, the publication of the ATTENTION generalizing results from the Chinese-only ATTENTION
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and BAOCHE trials provided crucial evidence for and BAOCHE cohorts, which may limit generalizability to
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the management of AIS due to BAO. ATTENTION, European populations due to genetic, lifestyle, and vascular
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published in October 2022, enrolled patients with BAO differences, including a higher prevalence of intracranial
within 12 h from symptom onset, focusing on those with atherosclerotic disease in the Chinese population.
moderate-to-severe symptoms (NIHSS ≥ 10) (Table 3). The Moreover, the results suggest a more pronounced benefit
study compared the combination of EVT plus BMT against of EVT in cases with lower use of IVT within the BMT
BMT alone, with primary outcomes centered on functional group, highlighting how the efficacy of combined therapy
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independence and mortality. BAOCHE, published in may depend on the proportion of patients receiving IVT.
April 2023, extended the treatment window up to 24 h For these reasons, current guidelines highlight the need
for late-presenting patients, similarly evaluating EVT for further studies to clarify patient selection and optimize
plus BMT versus BMT alone. These findings significantly IVT and EVT usage.
shaped ESO guidelines, demonstrating the advantages of
EVT in BAO patients within these defined time windows. 2.3. MT in AIS due to large vessel occlusion and large
ESO now endorses EVT combined with BMT, including ischemic cores
IVT when indicated, within a 24-h window for BAO General guidelines recommend MT plus IVT when
patients with NIHSS ≥ 10. Conversely, for NIHSS < 10, IVT indicated for LVO in anterior ischemic stroke within 0 – 6 h
alone is preferred, as EVT has not shown a clear benefit. if the infarct is limited (ASPECTS ≥ 6) and within 6 – 24 h
4
5
Nonetheless, for cases with extensive ischemic damage based on DAWN and DEFUSE-3 criteria, using advanced
(pc-ASPECTS 0 – 6), the ESO recommends assessing imaging for patient selection. Recent evidence supports
prognostic factors such as age and frailty before considering MT benefits for large ischemic core patients in anterior
reperfusion therapy and advises against it in cases with circulation strokes over medical management alone. Trials

Volume 3 Issue 3 (2025) 4 doi: 10.36922/bh.6683