ATCF (Azole Therapy in Cystic Fibrosis)

NCT ID: NCT01576315

Last Updated: 2023-05-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-06-30

Study Completion Date

2015-11-30

Brief Summary

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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

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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.

Conditions

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Cystic Fibrosis Aspergillus Infections

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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itraconazole

* 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

Group Type EXPERIMENTAL

Itraconazole/voriconazole

Intervention Type 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.

voriconazole

* 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

Group Type EXPERIMENTAL

Itraconazole/voriconazole

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Non applicable.

Eligibility Criteria

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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.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rennes University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean-Pierre Gangneux, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Service de parasito-mycologie - Rennes University Hospital

Locations

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CRCM Adulte et Pédiatrie - Hôpital Nord

Amiens, , France

Site Status

CRCM adulte - Centre Robert Debré

Angers, , France

Site Status

Pediatry - Centre Robert Debré

Angers, , France

Site Status

Pediatric penumologic - Groupe hospitalier de Pellegrin

Bordeaux, , France

Site Status

Pneumology pediatric - Hôpital Femme-Mère-Enfants

Bron, , France

Site Status

CRCM - Pediatry - CHI Créteil

Créteil, , France

Site Status

Service de Pneumologie-Immuno-Allergologie / Hôpital Calmette

Lille, , France

Site Status

Hôpital Nord - Pneumology

Marseille, , France

Site Status

Pneumologie Infantile - Hôpital des enfants

Nancy, , France

Site Status

CRCM - Hôpital Sud

Rennes, , France

Site Status

Pneumology - Hôpital Pontchaillou

Rennes, , France

Site Status

CRCM Pédiatrique - Hôpital de Hautepierre

Strasbourg, , France

Site Status

Pédiatrie - Pneumologie, Allergologie - Hôpital des enfants

Toulouse, , France

Site Status

Pneumology - CH Bretagne-Atlantique

Vannes, , France

Site Status

Manchester Adult Cystic Fibrosis Centre - University Hospital of South Manchester

Manchester, , United Kingdom

Site Status

Countries

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France United Kingdom

References

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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.

Reference Type RESULT
PMID: 35822920 (View on PubMed)

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.

Reference Type RESULT
PMID: 33680981 (View on PubMed)

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.

Reference Type RESULT
PMID: 36836250 (View on PubMed)

Other Identifiers

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2011-005799-41

Identifier Type: -

Identifier Source: org_study_id

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