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Study breakdown

CASTA: A Major Trial Testing Whether Peptide Therapy Can Help Stroke Patients Recover

Randomized Controlled Trial (Protocol/Design Paper)Moderate evidence
The takeaway

The CASTA trial randomized 1,060 stroke patients across Asia to receive cerebrolysin (a neurotrophic peptide mixture) or placebo within 12 hours of stroke onset, with 90-day disability outcomes.

1,060 patients

One of the largest randomized trials of a peptide-based neuroprotective therapy for acute stroke, across 50+ centers in Asia

What the researchers found

This paper describes the design of CASTA — one of the largest randomized controlled trials of cerebrolysin (a peptide mixture with neurotrophic and neuroprotective properties) for acute ischemic stroke. The trial enrolled 1,060 patients across 50+ centers in Asia, randomized within 12 hours of stroke onset to receive either 30 mL cerebrolysin or placebo IV daily for 10 days, added to standard care.

Primary efficacy was assessed at day 90 using three validated stroke outcome scales (modified Rankin Scale, Barthel Index, NIH Stroke Scale) combined into a single global test. The study design — large, double-blind, placebo-controlled, with 90-day follow-up — represented a significant step up from the smaller trials that had previously suggested cerebrolysin's efficacy in stroke.

Why it matters

Acute ischemic stroke has very few proven treatments — primarily clot-busting drugs (tPA) and mechanical thrombectomy, both with narrow time windows. A neuroprotective peptide therapy that could be given within 12 hours and reduce disability at 90 days would be a major advance. Cerebrolysin contains a mixture of neurotrophic peptides and amino acids that mimic the brain's natural repair factors. This trial tested whether the promising results from smaller studies would hold up in a large, rigorous multi-center trial.

The numbers in context

n=1,060 · 50+ centers in Asia · randomized within 12 hours of stroke · 30 mL cerebrolysin IV daily × 10 days · follow-up to 90 days · 3 stroke outcome scales

How the study worked

Double-blind, placebo-controlled, randomized trial across 50+ centers in Asia. Patients with acute ischemic hemispheric stroke were randomized within 12 hours of symptom onset to 30 mL cerebrolysin (diluted in saline) or placebo (saline) given as daily IV infusions for 10 days, added to standard stroke care. Efficacy evaluated at day 90 using modified Rankin Scale, Barthel Index, and NIH Stroke Scale combined into a global directional test.

Who was studied

1,060 patients with acute ischemic hemispheric stroke across 50+ centers in Asia, randomized within 12 hours of symptom onset

What this study cannot tell us

This paper describes the trial design, not the results — outcomes were pending at time of publication. The 12-hour treatment window is generous compared to thrombolysis (4.5 hours) and may dilute the effect if cerebrolysin works best when given early. The study was conducted exclusively in Asia, which may affect generalizability. Standard stroke care varied across 50+ centers. The mechanism of action of cerebrolysin (a complex peptide mixture) is not fully characterized, making it harder to optimize dosing.

How to read the evidence

This is a trial design paper (not results) for a large, well-designed double-blind RCT. The 'Moderate' grade reflects the high-quality study design while acknowledging that outcomes were not yet reported in this publication.

When this study was published

Published in 2009 as a trial design paper, CASTA results were subsequently published showing cerebrolysin did not meet its primary endpoint — though post-hoc analyses suggested benefits in certain subgroups. The trial remains important as one of the largest peptide neuroprotection studies in stroke.

The bigger picture

The search for effective neuroprotective therapies after stroke has been one of neurology's greatest challenges — dozens of drugs have failed in large trials despite promising preclinical data. Cerebrolysin, as a peptide-based approach that mimics natural neurotrophic factors, represents a different strategy from the small molecules that have failed. CASTA was one of the largest trials to test this concept, and its results (published subsequently) would significantly influence the field's view on peptide-based neuroprotection.

Questions still open

  • Did the CASTA trial ultimately show that cerebrolysin improved stroke outcomes at 90 days?
  • Would earlier treatment (within 6 hours rather than 12) produce better results?
  • Which specific peptide components of cerebrolysin are responsible for the neuroprotective effects?

Common questions

What is cerebrolysin and how does it work?
Cerebrolysin is a mixture of small neurotrophic peptides and amino acids derived from pig brain tissue. It mimics the brain's natural growth factors — the proteins that help neurons survive, grow, and form new connections. In animal stroke models, it reduced brain cell death and promoted recovery. The idea is that flooding the brain with these protective peptides during the critical window after a stroke could save neurons that would otherwise die.
Did this trial ultimately show that cerebrolysin works for stroke?
The results were mixed. CASTA did not meet its primary composite endpoint — meaning cerebrolysin did not show a statistically significant overall benefit across all three outcome measures combined. However, post-hoc analyses suggested potential benefits in specific subgroups, including patients with more severe strokes. This is a common pattern in neuroprotection trials, and the debate about cerebrolysin's role in stroke continues.

Read the original research

A double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of Cerebrolysin in patients with acute ischaemic stroke in Asia--CASTA.

International journal of stroke : official journal of the International Stroke Society, 4(5), 406-12

Citation

Hong, Z; Moessler, H; Bornstein, N; Brainin, M; Heiss, W-D. (2009). A double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of Cerebrolysin in patients with acute ischaemic stroke in Asia--CASTA.. International journal of stroke : official journal of the International Stroke Society, 4(5), 406-12. https://doi.org/10.1111/j.1747-4949.2009.00340.x