title: EMPIRICUS micafungin versus placebo during nosocomial sepsis in Candida multi-colonized ICU patients with multiple organ failures: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  The potential interest of antifungal treatment of non-immunocompromized patients with sepsis, extra-digestive Candida colonization and multiple organ failure is unknown. It represents three-quarters of antifungals prescribed in Intensive Care Units. It may allow early treatment of invasive fungal infection in the incubation phase but expose patients to unnecessary antifungal treatments with subsequent cost and fungal selection pressure. As early diagnostic tests for invasive candidiasis are still considered to be insufficient, the potential interest in this strategy needs to be demonstrated.
  
  
  METHODS
  This prospective multicenter, double blind, randomized-controlled trial is conducted in 23 French Intensive Care Units. All adult patients, mechanically ventilated for more than four days with sepsis of unknown origin and with at least one extradigestive fungal colonization site and multiple organ failure are eligible for randomization. Patients with proven invasive candidiasis are not included. After a complete mycological screening, patients are allocated to receive micafungin 100 mg intravenously once a day or placebo for 14 days. We plan to enroll 260 patients. The main objective is to demonstrate that micafungin increases survival of patients without invasive candidiasis at day 28 as compared to placebo. Other outcomes include day 28 and 90 survival and organ failure evolution. Additionally, pharmacokinetics of micafungin in enrolled patients will be measured and evolution of fungal biomarkers and susceptibility profiles of infecting fungi will also be followed.
  
  
  CONCLUSIONS
  This study will help to provide guidelines for treating non-immunocompromized patients with fungal colonization multiple organ failure and sepsis of unknown origin.
  
  
  BACKGROUND
  Clinicaltrials.gov number NCT01773876.
authors.affiliation: University Grenoble 1, Intensive Care Unit, Albert Michallon Hospital, BP 217, 38043 Grenoble, Cedex 9, France. JFTimsit@chu-grenoble.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Timsit
authors.forename: Elie
authors.initials: E
authors.lastname: Azoulay
authors.forename: Muriel
authors.initials: M
authors.lastname: Cornet
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gangneux
authors.forename: Vincent
authors.initials: V
authors.lastname: Jullien
authors.forename: Aurélien
authors.initials: A
authors.lastname: Vésin
authors.forename: Edith
authors.initials: E
authors.lastname: Schir
authors.forename: Michel
authors.initials: M
authors.lastname: Wolff
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use*; D058387:Candidemia / Q000188:drug therapy*; D002985:Clinical Protocols; D003428:Cross Infection / Q000188:drug therapy*; D004311:Double-Blind Method; D054714:Echinocandins / Q000627:therapeutic use*; D006801:Humans; D007362:Intensive Care Units; D055666:Lipopeptides / Q000627:therapeutic use*; D000077551:Micafungin; D009102:Multiple Organ Failure / Q000150:complications*; D011446:Prospective Studies
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077551:Micafungin