ATCF (Azole Therapy in Cystic Fibrosis)

Rennes University Hospital

Status and phase: Completed; Phase 2

Conditions: Aspergillus Infections; Cystic Fibrosis

Treatments: Drug: Itraconazole/voriconazole

Study type: Interventional

Funder types: Other

Identifiers

NCT01576315

2011-005799-41

Details and patient eligibility

About

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.

Full 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.

Enrollment: 11 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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11 participants in 2 patient groups

itraconazole

Experimental group

Description:

* itraconazole 10 mg/mL oral solution * patients \> 40 kg body weight : 200 mg morning and evening. * patients \< 40 kg body weight : 100 mg morning and evening. * dosage out of meal. * Without a loading dose

Treatment:

Drug: Itraconazole/voriconazole

voriconazole

Experimental group

Description:

* voriconazole 40 mg/mL oral suspension : * patients \> 40 kg body weight : 200 mg morning and evening. * patients \< 40 kg body weight : 100 mg morning and evening. * dosage out of meal. * Without a loading dose

Treatment:

Drug: Itraconazole/voriconazole