Aspergillus Infections, Cystic Fibrosis
Conditions
Keywords
cystic fibrosis, Aspergillus, itraconazole, voriconazole
Brief summary
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 aims to assess in patients with cystic fibrosis with persistent Aspergillus positive cultures the efficacy of itraconazole and voriconazole on the negativisation of the sputum cultures for Aspergillus.
Detailed description
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.
Interventions
DRUGItraconazole/voriconazole
The two treatments will be administered orally for 6 months One doage of treatment permitted based on plasma levels will be performed after two weeks of treatment.
Sponsors
Rennes University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient with cystic fibrosis, * men or women, * age equal greater to 12 years, * presenting with a positive sputum culture for Aspergillus confirmed twice within 6 months before study entry and at initial visit, * written informed consent.
Exclusion criteria
* patients with a contraindication to one of the antifungal agents evaluated, * pregnant women or nursing mothers, * absence of an effective method of contraception in women of child-bearing potential, * patients with signs or symptoms of invasive aspergillosis, * patients with signs or symptoms of aspergilloma, * patients with an infection caused by Burkholderia complex Cepacia or to mycobacteria, * lung transplant patients, registered on a transplantation waiting list or whose registration is imminent, * patients who received systemic antifungal therapy for more than 5 days within 2 months prior to inclusion, * patients currently enrolled in another clinical drug trial, * ongoing treatment with medicinal products contraindicated with itraconazole and voriconazole or with major interactions which reduce azole concentrations, * patients treated by medication known to prolong QT interval, or with known prolongation of QTc interval \> 450 msec in men and \> 470 msec in women, * Inability to follow or to understand the study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in percentage of patients with a negativisation of sputum cultures in 2 successive samples | Change from baseline in persentage of patients with a negativisation of sputum cultures at 4, 8, 16, 24 weeks after initiation of therapy | The primary evaluation criterion is the percentage of patients with a negativisation of sputum cultures in 2 successive samples, according to a standardised technique |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| safety of AFs including measurement of hepatic transaminases | at 2 weeks after initiation of therapy | safety of AFs including measurement of hepatic transaminases |
| number of courses of steroids and antibiotics recording | at 2 weeks after initiation of therapy | number of courses of steroids and antibiotics |
| quality of life | at 4, 8, 16 and 24 weeks after initiation of therapy | quality of life self-questionnaire scores, dyspnoea scale scores, 6 minute walking test, FEV1 value, and number of courses of steroids and antibiotics |
| plasma concentrations of antifungal agents | at 2 weeks after initiation of therapy | measurement of plasma concentrations of antifungal agents and testing at 4 weeks in case of dose adjustment. |
| safety profiles of the antifungal agents | at 4, 8, 16 and 24 weeks after initiation of therapy | safety profiles of the antifungal agents : impact of anti-fungal treatments on lung and systemic inflammation |
| mycological failures | after 1 month | 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 | at 2 weeks after initiation of therapy | number of adverse events recording |
| laboratory test indicators | at 4, 8, 16 and 24 weeks after initiation of therapy | course of different laboratory test indicators (sputum culture and PCR, IgG, total and specific IgE, eosinophilia) |
Countries
France, United Kingdom
Outcome results
None listed