title: Intravenous minocycline in acute stroke: a randomized, controlled pilot study and meta-analysis.
abstract: OBJECTIVE
  Minocycline, in animal models and 2 small randomized controlled human trials, is a promising neuroprotective agent in acute stroke. We analyzed the efficacy and safety of intravenous minocycline in acute ischemic and hemorrhagic stroke.
  
  
  METHODS
  A multicenter prospective randomized open-label blinded end point evaluation pilot study of minocycline 100 mg administered intravenously, commenced within 24 hours of onset of stroke, and continued 12 hourly for a total of 5 doses, versus no minocycline. All participants received routine stroke care. Primary end point was survival free of handicap (modified Rankin Scale, ≤2) at day 90.
  
  
  RESULTS
  Ninety-five participants were randomized; 47 to minocycline and 48 to no minocycline. In the intention-to-treat population, 29 of 47 (65.9%) allocated minocycline survived free of handicap compared with 33 of 48 (70.2%) allocated no minocycline (rate ratio, 0.94; 95% confidence interval, 0.71-1.25 and odds ratio, 0.73; 95% CI, 0.31-1.71). A meta-analysis of the 3 human trials suggests minocycline may increase the odds of handicap-free survival by 3-fold (odds ratio, 2.99; 95% CI, 1.74-5.16) but there was substantial heterogeneity among the trials.
  
  
  CONCLUSIONS
  In this pilot study of a small sample of acute stroke patients, intravenous minocycline was safe but not efficacious. The study was not powered to identify reliably or exclude a modest but clinically important treatment effect of minocycline. Larger trials would improve the precision of the estimates of any treatment effect of minocycline.
  
  
  BACKGROUND
  http://www.anzctr.org.au. Unique identifier: ACTRN12612000237886.
authors.affiliation: Royal Perth Hospital, Perth, Australia. Edith_Kohler@hotmail.com
authors.forename: Edith
authors.initials: E
authors.lastname: Kohler
authors.forename: David A
authors.initials: DA
authors.lastname: Prentice
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Bates
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: Anne
authors.initials: A
authors.lastname: Claxton
authors.forename: Jolandi
authors.initials: J
authors.lastname: van Heerden
authors.forename: David
authors.initials: D
authors.lastname: Blacker
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy*; D002543:Cerebral Hemorrhage / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D008911:Minocycline
keywords: hemorrhagic stroke; ischemic stroke; minocycline; neuroprotection; stroke