ATCF (Azole Therapy in Cystic Fibrosis)

• Change in percentage of patients with a negativisation of sputum cultures in 2 successive samples [ Time Frame: Change from baseline in persentage of patients with a negativisation of sputum cultures at 4, 8, 16, 24 weeks after initiation of therapy ] [ Designated as safety issue: No ]
  The primary evaluation criterion is the percentage of patients with a negativisation of sputum cultures in 2 successive samples, according to a standardised technique
  
  

• plasma concentrations of antifungal agents [ Time Frame: at 2 weeks after initiation of therapy ] [ Designated as safety issue: No ]
  measurement of plasma concentrations of antifungal agents and testing at 4 weeks in case of dose adjustment.
  
  
• safety of AFs including measurement of hepatic transaminases [ Time Frame: at 2 weeks after initiation of therapy ] [ Designated as safety issue: No ]
  safety of AFs including measurement of hepatic transaminases
  
  
• number of courses of steroids and antibiotics recording [ Time Frame: at 2 weeks after initiation of therapy ] [ Designated as safety issue: No ]
  number of courses of steroids and antibiotics
  
  
• quality of life [ Time Frame: at 4, 8, 16 and 24 weeks after initiation of therapy ] [ Designated as safety issue: No ]
  quality of life self-questionnaire scores, dyspnoea scale scores, 6 minute walking test, FEV1 value, and number of courses of steroids and antibiotics
  
  
• laboratory test indicators [ Time Frame: at 4, 8, 16 and 24 weeks after initiation of therapy ] [ Designated as safety issue: No ]
  course of different laboratory test indicators (sputum culture and PCR, IgG, total and specific IgE, eosinophilia)
  
  
• safety profiles of the antifungal agents [ Time Frame: at 4, 8, 16 and 24 weeks after initiation of therapy ] [ Designated as safety issue: Yes ]
  safety profiles of the antifungal agents : impact of anti-fungal treatments on lung and systemic inflammation
  
  
• mycological failures [ Time Frame: after 1 month ] [ Designated as safety issue: No ]
  analysis of mycological failures (defined as persistence of a positive culture) by a study over time of the course and outcome of fungal biodiversity of isolates (sequential study of chemosensitivity to different antifungal agents and molecular typing)
  
  
• number of adverse events recording [ Time Frame: at 2 weeks after initiation of therapy ] [ Designated as safety issue: No ]
  number of adverse events recording
  
  

Aspergillus infection is an infectious complication which frequently occurs in cystic fibrosis. The efficacy of azole therapy in patients with cystic fibrosis with persistent positive sputums for Aspergillus is still unknown. Furthermore, the efficacy of itraconazole and voriconazole in this indication has never been evaluated in a large prospective controlled clinical trial, even though many teams already use it.

The ATCF study is a prospective, multicenter, randomized, open-label, controlled phase II trial, performed in patients with cystic fibrosis with persistent Aspergillus positive cultures.

The primary outcome is to assess the efficacy of itraconazole and voriconazole on the course and outcome of the negativisation of the sputum cultures for Aspergillus on two consecutive cultures.

Secondary objectives include the effects of azole therapy on quality of life, FEV1, co-prescription of antibiotic and steroids, plasma concentrations of antifungal agents, speed of negativisation of sputum culture for Aspergillus, outcome of other diagnostic criteria (Aspergillus detection by PCR, precipiting antibodies, total and specific IgE, eosinophilia), and the safety profiles of the two products. Mycological failures, and impact of anti-fungal treatments on lung and systemic inflammation will also be assessed.