Tier 2 — strong

Fisetin Prolongs Therapy Window of Brain Ischemic Stroke Using Tissue Plasminogen Activator: A Double-Blind Randomized Placebo-Controlled Clinical Trial

Limin Wang, Di Cao, Huijun Wu, Hongning Jia, Chaoping Yang, Lihua Zhang
Clinical and Applied Thrombosis/Hemostasis 2019 25:1076029619871359

Bibliography

PubMed
PMID 31434498
PubMed Central
PMC6829632
DOI
10.1177/1076029619871359
Funding
The authors reported receiving no financial support for the research, authorship or publication.
Competing interests
The authors declared no potential conflicts of interest.

Study snapshot

DesignIntent-to-treat, randomized, double-blind, placebo-controlled clinical trial stratified by onset-to-treatment time.
ModelAdults with acute ischemic stroke receiving intravenous rt-PA, stratified to 0–3 hour or 3–5 hour onset-to-treatment windows.
Sample215 initially recruited; 192 eligible and randomized (130 in 0–3 h stratum, 62 in 3–5 h stratum).
Interventionrt-PA plus 100 mg fisetin at treatment initiation followed by 100 mg oral fisetin daily for 7 days, versus matched placebo.
Duration7 days of fisetin/placebo treatment with acute outcome assessments.
EndpointsNIH Stroke Scale (NIHSS); Serum MMP-2; Serum MMP-9; C-reactive protein; Treatment response by onset-to-treatment stratum

What the study showed, in plain terms

This trial tested fisetin as an adjunct to rt-PA in acute ischemic stroke, not as a general brain-health supplement. The clearest signal appeared in patients treated 3–5 hours after stroke onset, where fisetin was associated with better short-term neurological scores than placebo.

Fisetin also lowered MMP-2, MMP-9 and CRP, biomarkers relevant to inflammation and blood-brain-barrier injury. The result is clinically interesting but highly condition-specific and should not be generalized to memory enhancement, dementia prevention or routine fisetin use.

Key findings

  • In the standard 0–3 hour rt-PA window, early NIHSS outcomes were not significantly different between fisetin and placebo.
  • In the delayed 3–5 hour stratum, fisetin was associated with improved NIHSS outcomes relative to placebo.
  • MMP-2, MMP-9 and CRP were reduced with fisetin and correlated with neurological scores.

What this study can and cannot tell us

  • Single-center acute-stroke study; replication in independent centers and modern stroke-care settings is needed.
  • Short treatment and follow-up focus on acute outcomes rather than long-term disability or cognition.
  • The paper notes that coexisting infection or in-hospital infectious complications were not analyzed, which could confound CRP.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology