title: High-dose intravenous methylprednisolone for hantavirus cardiopulmonary syndrome in Chile: a double-blind, randomized controlled clinical trial.
abstract: BACKGROUND
  Andes virus (ANDV)-related hantavirus cardiopulmonary syndrome (HCPS) has a 35% case fatality rate in Chile and no specific treatment. In an immunomodulatory approach, we evaluated the efficacy of intravenous methylprednisolone for HCPS treatment, through a parallel-group, placebo-controlled clinical trial.
  
  
  METHODS
  Patients aged >2 years, with confirmed or suspected HCPS in cardiopulmonary stage, admitted to any of 13 study sites in Chile, were randomized by study center in blocks of 4 with a 1:1 allocation and assigned through sequentially numbered envelopes to receive placebo or methylprednisolone 16 mg/kg/day (≤1000 mg) for 3 days. All personnel remained blinded except the local pharmacist. Infection was confirmed by immunoglobulin M antibodies or ANDV RNA in blood. The composite primary endpoint was death, partial pressure of arterial oxygen/fraction of inspired oxygen ratio ≤55, cardiac index ≤2.2, or ventricular tachycardia or fibrillation within 28 days. Safety endpoints included the number of serious adverse events (SAEs) and quantification of viral RNA in blood. Analysis was by intention to treat.
  
  
  RESULTS
  Infection was confirmed in 60 of 66 (91%) enrollees. Fifteen of 30 placebo-treated patients and 11 of 30 methylprednisolone-treated patients progressed to the primary endpoint (P = .43). We observed no significant difference in mortality between treatment groups (P = .41). There was a trend toward more severe disease in placebo recipients at entry. More subjects in the placebo group experienced SAEs (P = .02). There were no SAEs clearly related to methylprednisolone administration, and methylprednisolone did not increase viral load.
  
  
  CONCLUSIONS
  Although methylprednisolone appears to be safe, it did not provide significant clinical benefit to patients. Our results do not support the use of methylprednisolone for HCPS.
  
  
  BACKGROUND
  NCT00128180.
authors.affiliation: Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago.
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Vial
authors.forename: Francisca
authors.initials: F
authors.lastname: Valdivieso
authors.forename: Marcela
authors.initials: M
authors.lastname: Ferres
authors.forename: Raul
authors.initials: R
authors.lastname: Riquelme
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Rioseco
authors.forename: Mario
authors.initials: M
authors.lastname: Calvo
authors.forename: Constanza
authors.initials: C
authors.lastname: Castillo
authors.forename: Ricardo
authors.initials: R
authors.lastname: Díaz
authors.forename: Luis
authors.initials: L
authors.lastname: Scholz
authors.forename: Analia
authors.initials: A
authors.lastname: Cuiza
authors.forename: Edith
authors.initials: E
authors.lastname: Belmar
authors.forename: Carla
authors.initials: C
authors.lastname: Hernandez
authors.forename: Jessica
authors.initials: J
authors.lastname: Martinez
authors.forename: Sang-Joon
authors.initials: SJ
authors.lastname: Lee
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Mertz
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002677:Chile; D004311:Double-Blind Method; D005260:Female; D006476:Orthohantavirus / Q000235:genetics / Q000302:isolation & purification; D018804:Hantavirus Pulmonary Syndrome / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D012367:RNA, Viral; D008775:Methylprednisolone
keywords: clinical trial; hantavirus; hantavirus cardiopulmonary syndrome; hantavirus pulmonary syndrome; methylprednisolone