title: Placebo-controlled, double-blind trial of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome in North America.
abstract: BACKGROUND. Ribavirin is active in vitro against hantaviruses, but the findings of an open trial of the use of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome (HCPS) were inconclusive.
  
  
  METHODS
  Subjects with suspected HCPS in the prodrome or cardiopulmonary phase but without shock were eligible for randomization to receive either intravenous ribavirin (33 mg/kg [<or=2 g], followed by 16 mg/kg [<or=1 g] given every 6 h for 4 days and by 8 mg/kg [<or=.5 g] given every 8 h for 3 days) or placebo (administered for 7 days or until the initial Sin Nombre virus antibody test result was confirmed to be negative). The primary outcome was survival at day 28 of the study without the need for extracorporeal membrane oxygenation (ECMO).
  
  
  RESULTS
  Thirty-six subjects were enrolled in the trial from March 1996 through July 2001, at which point the study was terminated prematurely because of both the slow rate of accrual of subjects and the findings of a futility analysis. Of the 36 subjects enrolled, 23 (all of whom were enrolled during the cardiopulmonary stage of HCPS) had HCPS confirmed by serologic testing. The severity of illness at entry into the study was similar among the 10 subjects with HCPS who received ribavirin and the 13 subjects with HCPS who received placebo. The proportion of subjects who survived and who did not require ECMO was similar among ribavirin recipients and placebo recipients (70% vs. 62%, respectively); 2 ribavirin recipients and 2 placebo recipients died, including 3 of 7 subjects treated with ECMO. The frequency of adverse events, including anemia, was similar between treatment groups.
  
  
  CONCLUSIONS
  The rate of accrual of subjects in the present study was inadequate to clearly assess the safety or efficacy of ribavirin in the treatment of HCPS. However, ribavirin was well tolerated, and the lack of trends supporting the use of intravenous ribavirin suggests that it is probably ineffective in the treatment of HCPS in the cardiopulmonary stage.
authors.affiliation: Internal Medicine, University of New Mexico, Albuquerque, New Mexico 87131-0001, USA. gmertz@salud.unm.edu
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Mertz
authors.forename: Lil
authors.initials: L
authors.lastname: Miedzinski
authors.forename: Diane
authors.initials: D
authors.lastname: Goade
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Pavia
authors.forename: Brian
authors.initials: B
authors.lastname: Hjelle
authors.forename: Christine O
authors.initials: CO
authors.lastname: Hansbarger
authors.forename: Howard
authors.initials: H
authors.lastname: Levy
authors.forename: Frederick T
authors.initials: FT
authors.lastname: Koster
authors.forename: Kenneth
authors.initials: K
authors.lastname: Baum
authors.forename: Adeline
authors.initials: A
authors.lastname: Lindemulder
authors.forename: Wenquan
authors.initials: W
authors.lastname: Wang
authors.forename: Laura
authors.initials: L
authors.lastname: Riser
authors.forename: Humberto
authors.initials: H
authors.lastname: Fernandez
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Whitley
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D018804:Hantavirus Pulmonary Syndrome / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009656:North America / Q000453:epidemiology; D010919:Placebos; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D010919:Placebos; D012254:Ribavirin