Empirical Antifungal Treatment in ICUS (EMPIRICUS)

• survival to 28 days without proven fungal infection (a fungal infection occurring within 48 hours after inclusion will be considered available for inclusion) [ Time Frame: 28 days follow-up ] [ Designated as safety issue: No ]
  breakthrough infection defined as a proven infection occurs at least 48 hours after initiation of treatment Proven infection is considered purchased after enrollment if the first significant positive levy occurs after the 48 th hour after enrollment.
  
  

• pharmacokinetic parameters: estimated gross exposure indices: AUC, Cmax, Cmin [ Time Frame: during 24 hours (between the two first infusions) ] [ Designated as safety issue: No ]
  Reports AUC / MIC and Cmax / MIC will be calculated
  
  
• evaluation of tolerance [ Time Frame: 3 months ] [ Designated as safety issue: No ]

  For all patients who received at least one dose of treatment:

  • number of adverse events reported after randomization up to 28 days, only death will count up to 3 months post-randomization (information on the long-term survival collected by telephone),
  • changes in the clinical examination, vital signs and laboratory results,
  • overall survival defined as the time from randomization to date of death from any cause.
  • Changes in liver function tests (bilirubin, ALT, AST, rate prothrombin, alkaline phosphatase) at the end of treatment and at the end study
  
  
• pharmacodynamic parameters: potential serum biomarkers of treatment efficacy (PCR Candida,1,3 β-D-glucan,mannan antigenemia,anti-mannan,Procalcitonin (proCT)) [ Time Frame: during 28 days ] [ Designated as safety issue: No ]
  
• pharmacodynamic parameters: Early prognostic factors of response: J7 survival without proven invasive candidiasis [ Time Frame: during 14 days ] [ Designated as safety issue: No ]
  
• Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible on all-cause mortality at day 28 (end of study) and J90 (3 months post-randomization) [ Time Frame: during 90 days ] [ Designated as safety issue: No ]
  
• Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis can free survival antifungal treatment at day 28 [ Time Frame: during 28 days ] [ Designated as safety issue: No ]
  
• Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible evolution of organ failure during the study [ Time Frame: during 90 days ] [ Designated as safety issue: No ]
  
• Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible the use of mechanical ventilation during the study [ Time Frame: during 90 days ] [ Designated as safety issue: No ]
  
• Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible evolution of the colonization index during study [ Time Frame: during 90 days ] [ Designated as safety issue: No ]
  
• Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible changes in serum biomarkers (1-3 β-D-glucan, mannan antigenemia, anti-mannan Candida PCR) during the study [ Time Frame: during 90 days ] [ Designated as safety issue: No ]
  
• Evaluate the impact of empiric treatment with micafungin in patients with invasive candidiasis possible on the incidence of pneumonia acquired bacterial mechanical ventilation (VAP). [ Time Frame: during 90 days ] [ Designated as safety issue: No ]
  

Multicenter, randomized, double-blind parallel groups comparing adult patients with suspected invasive candidiasis input from a 14-day empirical treatment with micafungin (MYCAMINE 100 mg) with placebo on survival without invasive candidiasis in 28 days after initiation of study treatment.