title: Human choriogonadotropin and epoetin alfa in acute ischemic stroke patients (REGENESIS-LED trial).
abstract: BACKGROUND
  Preclinical studies suggest that growth factors in the early days after stroke improve final outcome. A prior study found three doses of human choriogonadotropin alfa followed by three doses of erythropoietin to be safe after stroke in humans. A proof of concept trial (REGENESIS) was initiated but placed on regulatory hold during review of an erythropoietin neuroprotective trial. Due to financial constraints, the trial was largely moved to India, using lower erythropoietin doses, as the REGENESIS-LED trial.
  
  
  METHODS
  Entry criteria included National Institutes of Health Stroke Scale 8-20, supratentorial ischemic stroke, and 24-48 h poststroke at start of therapy. Patients were randomized to three QOD doses of subcutaneous human choriogonadotropin alfa followed by three QD doses of intravenous erythropoietin (three escalating dose cohorts, 4000-20,000 IU/dose) vs. placebo. Primary outcomes were safety and neurological recovery.
  
  
  RESULTS
  The study was halted early by the sponsor after 96 enrollees. There was no significant difference across treatment groups in the proportion of patients experiencing death, serious adverse events, or any adverse event. There was no significant difference in National Institutes of Health Stroke Scale score change from baseline to Day 90 between placebo and active treatment, whether active cohorts were analyzed together or separately, and no exploratory secondary measure of neurological recovery showed a significant difference between groups.
  
  
  CONCLUSIONS
  Administration of human choriogonadotropin alfa followed by erythropoietin is safe after a new ischemic stroke. At the doses studied, placebo and active groups did not differ significantly in neurological recovery. Study limitations, such as the use of multiple assessors, differences in rehabilitation care, and being underpowered to show efficacy, are discussed.
authors.affiliation: Departments of Neurology and Anatomy & Neurobiology, University of California, Irvine, CA, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Cramer
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hill
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000150:complications; D006063:Chorionic Gonadotropin / Q000627:therapeutic use*; D015331:Cohort Studies; D004311:Double-Blind Method; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D007391:International Cooperation; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D017063:Outcome Assessment, Health Care; D011994:Recombinant Proteins / Q000627:therapeutic use; D012720:Severity of Illness Index; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors; D015898:Tomography Scanners, X-Ray Computed; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006063:Chorionic Gonadotropin; D006397:Hematinics; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa
keywords: clinical trial; growth factor; restorative; safety; stroke recovery