title: Lovastatin for adult patients with dengue: protocol for a randomised controlled trial.
abstract: BACKGROUND
  Dengue is the most important vector-borne viral infection of man, with approximately 2 billion people living in areas at risk. Infection results in a range of manifestations from asymptomatic infection through to life-threatening shock and haemorrhage. One of the hallmarks of severe dengue is vascular endothelial disruption. There is currently no specific therapy and clinical management is limited to supportive care. Statins are a class of drug initially developed for lipid lowering. There has been considerable recent interest in their effects beyond lipid lowering. These include anti-inflammatory effects at the endothelium. In addition, it is possible that lovastatin may have an anti-viral effect against dengue. Observational data suggest that the use of statins may improve outcomes for such conditions as sepsis and pneumonia. This paper describes the protocol for a randomised controlled trial investigating a short course of lovastatin therapy in adult patients with dengue.
  
  
  METHODS
  A randomised, double-blind, placebo-controlled trial will investigate the effects of lovastatin therapy in the treatment of dengue. The trial will be conducted in two phases with an escalation of dose between phases if an interim safety review is satisfactory. This is an exploratory study focusing on safety and there are no data on which to base a sample size calculation. A target sample size of 300 patients in the second phase, enrolled over two dengue seasons, was chosen based on clinical judgement and feasibility considerations. In a previous randomised trial in dengue, about 10% and 30% of patients experienced at least one serious adverse event or adverse event, respectively. With 300 patients, we will have 80% power to detect an increase of 12% (from 10% to 22%) or 16% (from 30% to 46%) in the frequency of adverse events. Furthermore, this sample size ensures some power to explore the efficacy of statins.
  
  
  CONCLUSIONS
  The development of a dengue therapeutic that can attenuate disease would be an enormous advance in global health. The favourable effects of statins on the endothelium, their good safety profile and their low cost make lovastatin an attractive therapeutic candidate.
  
  
  BACKGROUND
  International Standard Randomised Controlled Trial Number ISRCTN03147572.
authors.affiliation: Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK. james.whitehorn@lshtm.ac.uk
authors.forename: James
authors.initials: J
authors.lastname: Whitehorn
authors.forename: Nguyen
authors.initials: N
authors.lastname: Van Vinh Chau
authors.forename: Nguyen Thanh
authors.initials: NT
authors.lastname: Truong
authors.forename: Luong Thi Hue
authors.initials: LT
authors.lastname: Tai
authors.forename: Nguyen
authors.initials: N
authors.lastname: Van Hao
authors.forename: Tran Tinh
authors.initials: TT
authors.lastname: Hien
authors.forename: Marcel
authors.initials: M
authors.lastname: Wolbers
authors.forename: Laura
authors.initials: L
authors.lastname: Merson
authors.forename: Nguyen Thi Phuong
authors.initials: NT
authors.lastname: Dung
authors.forename: Rosanna
authors.initials: R
authors.lastname: Peeling
authors.forename: Cameron
authors.initials: C
authors.lastname: Simmons
authors.forename: Bridget
authors.initials: B
authors.lastname: Wills
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
mesh_terms: D003715:Dengue / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D004739:England; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D008148:Lovastatin / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D018401:Sample Size; D013997:Time Factors; D016896:Treatment Outcome; D014744:Vietnam
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin