Compounds with a graded row

Ordered by rung, strongest first. The rung rates the study design; the chip beside it says what the study measured. Both are needed.

1. Cerebrolysin

   human RCT Direct outcome Approved for this condition

   Who was studied

   adults with acute ischaemic stroke confirmed on neuroimaging, treated within 48 hours of onset; 7 randomised trials, n=1773 (1689 analysed), mean age approximately 60-69, follow-up 28-90 days; haemorrhagic stroke and the recovery phase were not covered

   Approved and marketed in Russia, China and parts of Eastern Europe, and recommended for acute ischaemic stroke by Russian national clinical practice guidelines; it is not approved by the FDA or the EMA. The 2023 Cochrane review of 7 randomised trials found it probably makes little to no difference to all-cause death (RR 0.96, 95% CI 0.65-1.41, moderate certainty) and probably increases non-fatal serious adverse events (RR 2.39, 95% CI 1.10-5.23, moderate certainty); no included trial reported death-or-dependence, quality of life or return to work. The reviewers judged allocation concealment unclear in 6 of 7 trials, attrition of 16-29% in 4 trials, and two trials at high risk of bias from manufacturer involvement; with fewer than 10 trials they could not test for publication bias by funnel plot.

   Source DOI 1 primary source read for this row

2. Cortexin

   human RCT Direct outcome Approved for this condition

   Who was studied

   adults with acute ischaemic stroke in the internal carotid artery territory, intracerebral haemorrhage excluded by CT or MRI, treatment started within 24 hours of onset; n=272, double-blind, placebo-controlled, 70 days

   Approved in Russia and recommended there for acute ischaemic stroke by national clinical practice guidelines; it is not approved by the FDA or the EMA and no EMA or FDA assessment of it exists on file. The single trial, published in Russian, reported benefit from two courses of 10 mg intramuscularly three times daily; the 2023 Cochrane review of Cerebrolysin included this same trial as a Cerebrolysin-like cattle-brain preparation and concluded that adding Cerebrolysin or Cortexin to standard therapy probably does not reduce the risk of dying and increases non-fatal serious adverse events. No trial in haemorrhagic stroke or in the recovery phase is on file.

   Source PubMed 2 primary sources read for this row

3. Semax

   human observational Direct outcome Approval not established

   Who was studied

   adults in the recovery phase after ischaemic stroke, n=110 (43 men, 67 women, mean age 58.0 plus or minus 9.7), entering rehabilitation at 89 plus or minus 9 days (early) or 214 plus or minus 22 days (late); acute stroke and haemorrhagic stroke were not studied

   The one located human study measured Barthel index, MRC motor scale and plasma BDNF in post-stroke rehabilitation patients split into semax and no-semax subgroups; the report does not state that allocation was randomised, placebo-controlled or blinded, so it is graded as observational. It is not approved by the FDA or the EMA; a Russian registration for ischaemic stroke is widely asserted but no regulator document was located, so approval status is recorded as unknown rather than guessed. No study of semax in acute or haemorrhagic stroke is on file.

   Source PubMed 1 primary source read for this row

Checked, and nothing recorded

5 compounds were checked against stroke and produced no gradeable row.

• Adamax — checked, no row on file
• Dihexa — checked, no row on file
• Noopept — checked, no row on file
• P21 — checked, no row on file
• Pinealon — checked, no row on file

A compound is here because someone looked and the sources did not support a row — not because nobody looked. Under the rubric, uncertainty resolves to no row, and a row resting on a vendor page or a clinic blog is worse than no row at all.