ATCF (Azole Therapy in Cystic Fibrosis)

NCT01576315 | Completed Phase 2

• 1 other identifier: 2011-005799-41
• Study Type: interventional
• Target: 11
• Locations: 2 countries
• Sites: 15

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.

Conditions

Cystic Fibrosis; Aspergillus Infections

Keywords

cystic fibrosis; Aspergillus; itraconazole; voriconazole

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• plasma concentrations of antifungal agents

  at 2 weeks after initiation of therapy

• safety of AFs including measurement of hepatic transaminases

  at 2 weeks after initiation of therapy

• number of courses of steroids and antibiotics recording

  at 2 weeks after initiation of therapy

• quality of life

  at 4, 8, 16 and 24 weeks after initiation of therapy

• laboratory test indicators

  at 4, 8, 16 and 24 weeks after initiation of therapy

Study Arms (2)

itraconazole

EXPERIMENTAL

* 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

Drug: Itraconazole/voriconazole

voriconazole

EXPERIMENTAL

* 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

Drug: Itraconazole/voriconazole

Interventions

Itraconazole/voriconazole DRUG

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.

Also known as: Non applicable.

itraconazole; voriconazole

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Rennes University Hospital: lead

Study Sites (15)

CRCM Adulte et Pédiatrie - Hôpital Nord

Amiens, 80054, France

Location

CRCM adulte - Centre Robert Debré

Angers, 49033, France

Location

Pediatry - Centre Robert Debré

Angers, 49033, France

Location

Pediatric penumologic - Groupe hospitalier de Pellegrin

Bordeaux, 33000, France

Location

Pneumology pediatric - Hôpital Femme-Mère-Enfants

Bron, 69500, France

Location

CRCM - Pediatry - CHI Créteil

Créteil, 94000, France

Location

Service de Pneumologie-Immuno-Allergologie / Hôpital Calmette

Lille, 59037, France

Location

Hôpital Nord - Pneumology

Marseille, 13015, France

Location

Pneumologie Infantile - Hôpital des enfants

Nancy, 54577, France

Location

CRCM - Hôpital Sud

Rennes, 35000, France

Location

Pneumology - Hôpital Pontchaillou

Rennes, 35000, France

Location

CRCM Pédiatrique - Hôpital de Hautepierre

Strasbourg, 67098, France

Location

Pédiatrie - Pneumologie, Allergologie - Hôpital des enfants

Toulouse, 31059, France

Location

Pneumology - CH Bretagne-Atlantique

Vannes, 56017, France

Location

Manchester Adult Cystic Fibrosis Centre - University Hospital of South Manchester

Manchester, M23 9LT, United Kingdom

Location

Related 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.

  PMID: 35822920 RESULT

• 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/fcimb.2020.613774. eCollection 2020.

  PMID: 33680981 RESULT

• 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):134. doi: 10.3390/jof9020134.

  PMID: 36836250 RESULT

MeSH Terms

Conditions

Cystic Fibrosis; Aspergillosis

Interventions

Itraconazole; Voriconazole

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Mycoses; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Officials

• Jean-Pierre Gangneux, MD, PhD

  Service de parasito-mycologie - Rennes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2012
• First Posted: April 12, 2012
• Study Start: June 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: November 1, 2015
• Last Updated: May 24, 2023

Record last verified: 2023-05

Locations

FR (14); GB (1)