ATCF (Azole Therapy in Cystic Fibrosis)

Cystic Fibrosis Clinical Trial

— ATCF  

Official title:

Efficacy of Itraconazole and of Voriconazole in Patients With Cystic Fibrosis and Presenting With Persistent Positive Sputums for Aspergillus.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01576315
• Other study ID #: 2011-005799-41
• Status: Completed
• Phase: Phase 2
• Start date: June 2014
• Est. completion date: November 2015

Study information

• Verified date: May 2023
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: November 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Aspergillosis
• Aspergillus Infections
• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Itraconazole/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.

Locations

Country	Name	City	State
France	CRCM Adulte et Pédiatrie - Hôpital Nord	Amiens
France	CRCM adulte - Centre Robert Debré	Angers
France	Pediatry - Centre Robert Debré	Angers
France	Pediatric penumologic - Groupe hospitalier de Pellegrin	Bordeaux
France	Pneumology pediatric - Hôpital Femme-Mère-Enfants	Bron
France	CRCM - Pediatry - CHI Créteil	Créteil
France	Service de Pneumologie-Immuno-Allergologie / Hôpital Calmette	Lille
France	Hôpital Nord - Pneumology	Marseille
France	Pneumologie Infantile - Hôpital des enfants	Nancy
France	CRCM - Hôpital Sud	Rennes
France	Pneumology - Hôpital Pontchaillou	Rennes
France	CRCM Pédiatrique - Hôpital de Hautepierre	Strasbourg
France	Pédiatrie - Pneumologie, Allergologie - Hôpital des enfants	Toulouse
France	Pneumology - CH Bretagne-Atlantique	Vannes
United Kingdom	Manchester Adult Cystic Fibrosis Centre - University Hospital of South Manchester	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Countries where clinical trial is conducted

France,  United Kingdom, 

References & Publications (3)

Gangneux JP, Godet C, Denning DW. Allergic diseases and fungal exposome: Prevention is better than cure. Allergy. 2022 Nov;77(11):3182-3184. doi: 10.1111/all.15436. No abstract available. — View Citation

Guegan H, Poirier W, Ravenel K, Dion S, Delabarre A, Desvillechabrol D, Pinson X, Sergent O, Gallais I, Gangneux JP, Giraud S, Gastebois A. Deciphering the Role of PIG1 and DHN-Melanin in Scedosporium apiospermum Conidia. J Fungi (Basel). 2023 Jan 18;9(2) — View Citation

Guegan H, Prat E, Robert-Gangneux F, Gangneux JP. Azole Resistance in Aspergillus fumigatus: A Five-Year Follow Up Experience in a Tertiary Hospital With a Special Focus on Cystic Fibrosis. Front Cell Infect Microbiol. 2021 Feb 18;10:613774. doi: 10.3389/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in percentage of patients with a negativisation of sputum cultures in 2 successive samples	The primary evaluation criterion is the percentage of patients with a negativisation of sputum cultures in 2 successive samples, according to a standardised technique	Change from baseline in persentage of patients with a negativisation of sputum cultures at 4, 8, 16, 24 weeks after initiation of therapy
Secondary	plasma concentrations of antifungal agents	measurement of plasma concentrations of antifungal agents and testing at 4 weeks in case of dose adjustment.	at 2 weeks after initiation of therapy
Secondary	safety of AFs including measurement of hepatic transaminases	safety of AFs including measurement of hepatic transaminases	at 2 weeks after initiation of therapy
Secondary	number of courses of steroids and antibiotics recording	number of courses of steroids and antibiotics	at 2 weeks after initiation of therapy
Secondary	quality of life	quality of life self-questionnaire scores, dyspnoea scale scores, 6 minute walking test, FEV1 value, and number of courses of steroids and antibiotics	at 4, 8, 16 and 24 weeks after initiation of therapy
Secondary	laboratory test indicators	course of different laboratory test indicators (sputum culture and PCR, IgG, total and specific IgE, eosinophilia)	at 4, 8, 16 and 24 weeks after initiation of therapy
Secondary	safety profiles of the antifungal agents	safety profiles of the antifungal agents : impact of anti-fungal treatments on lung and systemic inflammation	at 4, 8, 16 and 24 weeks after initiation of therapy
Secondary	mycological failures	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)	after 1 month
Secondary	number of adverse events recording	number of adverse events recording	at 2 weeks after initiation of therapy