title: Trafermin for stroke recovery: is it time for another randomized clinical trial?
abstract: BACKGROUND
  Basic fibroblast growth factor (bFGF) has been shown to reduce volume in acute ischemic stroke models, and to promote functional recovery as well as new synapse formation when given to animals with completed cerebral infarction. A recombinant native form of human bFGF, trafermin, has been tested in Phase III clinical trials in patients with stroke.
  
  
  METHODS
  The role of trafermin in stroke. Data were identified by searching PubMed for single or combined terms including: trafermin, basic fibroblast growth factors, neuroprotection, neuroprotective drugs, stroke therapy, stroke rehabilitation and acute stroke. Original research papers, clinical series and reviews are included. Our research covered all relevant data up until 1 April 2011.
  
  
  CONCLUSIONS
  To date, all Phase III trials have failed to demonstrate the superiority of trafermin over placebo when given within 6 h from stroke onset because trafermin causes a dose-dependent hypotension and an increased mortality rate in treated patients. However, a 24-h intravenous infusion seems to be safe for stroke patients and may result in an improved outcome when given 5 - 6 h after infarct. This finding may open renewed interest in restorative treatment for stroke, which could enhance recovery mechanisms rather than immediate neuroprotection. Studies suggest that growth factors can produce improvement in animal models of stroke, even when administered at postischemic intervals from many hours to days, when conventional neuroprotective approaches are typically ineffective. Because of the number of side effects and increased mortality reported in the first clinical studies with high dose of FGF, further experimental studies are necessary to asses whether it is possible to achieve a pharmacologically significant therapeutic level in the brain, by minimizing peripheral side effects. Another randomized clinical trial is needed to test trafermin in stroke patients but to enhance functional recovery.
authors: University of Perugia, Santa Maria della Misericordia Hospital, Stroke Unit and Division of Cardiovascular Medicine, Sant'Andrea delle Fratte, Perugia, 06126, Italy. mpaciaroni@med.unipg.it
authors: Maurizio
authors: M
authors: Paciaroni
authors: Julien
authors: J
authors: Bogousslavsky
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000401:mortality; D019317:Evidence-Based Medicine; D005346:Fibroblast Growth Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D010446:Peptide Fragments; C114444:trafermin; D005346:Fibroblast Growth Factors