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ATCF (Azole Therapy in Cystic Fibrosis) (ATCF)

Primary Purpose

Cystic Fibrosis, Aspergillus Infections

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Itraconazole/voriconazole
Sponsored by
Rennes University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring cystic fibrosis, Aspergillus, itraconazole, voriconazole

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • CRCM Adulte et Pédiatrie - Hôpital Nord
  • CRCM adulte - Centre Robert Debré
  • Pediatry - Centre Robert Debré
  • Pediatric penumologic - Groupe hospitalier de Pellegrin
  • Pneumology pediatric - Hôpital Femme-Mère-Enfants
  • CRCM - Pediatry - CHI Créteil
  • Service de Pneumologie-Immuno-Allergologie / Hôpital Calmette
  • Hôpital Nord - Pneumology
  • Pneumologie Infantile - Hôpital des enfants
  • CRCM - Hôpital Sud
  • Pneumology - Hôpital Pontchaillou
  • CRCM Pédiatrique - Hôpital de Hautepierre
  • Pédiatrie - Pneumologie, Allergologie - Hôpital des enfants
  • Pneumology - CH Bretagne-Atlantique
  • Manchester Adult Cystic Fibrosis Centre - University Hospital of South Manchester

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

itraconazole

voriconazole

Arm 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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

plasma concentrations of antifungal agents
measurement of plasma concentrations of antifungal agents and testing at 4 weeks in case of dose adjustment.
safety of AFs including measurement of hepatic transaminases
safety of AFs including measurement of hepatic transaminases
number of courses of steroids and antibiotics recording
number of courses of steroids and antibiotics
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
laboratory test indicators
course of different laboratory test indicators (sputum culture and PCR, IgG, total and specific IgE, eosinophilia)
safety profiles of the antifungal agents
safety profiles of the antifungal agents : impact of anti-fungal treatments on lung and systemic inflammation
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)
number of adverse events recording
number of adverse events recording

Full Information

First Posted
March 29, 2012
Last Updated
May 22, 2023
Sponsor
Rennes University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01576315
Brief Title
ATCF (Azole Therapy in Cystic Fibrosis)
Acronym
ATCF
Official Title
Efficacy of Itraconazole and of Voriconazole in Patients With Cystic Fibrosis and Presenting With Persistent Positive Sputums for Aspergillus.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
June 2014 (undefined)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rennes University Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis, Aspergillus Infections
Keywords
cystic fibrosis, Aspergillus, itraconazole, voriconazole

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Pierre Gangneux, MD, PhD
Organizational Affiliation
Service de parasito-mycologie - Rennes University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
CRCM Adulte et Pédiatrie - Hôpital Nord
City
Amiens
ZIP/Postal Code
80054
Country
France
Facility Name
CRCM adulte - Centre Robert Debré
City
Angers
ZIP/Postal Code
49033
Country
France
Facility Name
Pediatry - Centre Robert Debré
City
Angers
ZIP/Postal Code
49033
Country
France
Facility Name
Pediatric penumologic - Groupe hospitalier de Pellegrin
City
Bordeaux
ZIP/Postal Code
33000
Country
France
Facility Name
Pneumology pediatric - Hôpital Femme-Mère-Enfants
City
Bron
ZIP/Postal Code
69500
Country
France
Facility Name
CRCM - Pediatry - CHI Créteil
City
Créteil
ZIP/Postal Code
94000
Country
France
Facility Name
Service de Pneumologie-Immuno-Allergologie / Hôpital Calmette
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Hôpital Nord - Pneumology
City
Marseille
ZIP/Postal Code
13015
Country
France
Facility Name
Pneumologie Infantile - Hôpital des enfants
City
Nancy
ZIP/Postal Code
54577
Country
France
Facility Name
CRCM - Hôpital Sud
City
Rennes
ZIP/Postal Code
35000
Country
France
Facility Name
Pneumology - Hôpital Pontchaillou
City
Rennes
ZIP/Postal Code
35000
Country
France
Facility Name
CRCM Pédiatrique - Hôpital de Hautepierre
City
Strasbourg
ZIP/Postal Code
67098
Country
France
Facility Name
Pédiatrie - Pneumologie, Allergologie - Hôpital des enfants
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Pneumology - CH Bretagne-Atlantique
City
Vannes
ZIP/Postal Code
56017
Country
France
Facility Name
Manchester Adult Cystic Fibrosis Centre - University Hospital of South Manchester
City
Manchester
ZIP/Postal Code
M23 9LT
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
35822920
Citation
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.
Results Reference
result
PubMed Identifier
33680981
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/fcimb.2020.613774. eCollection 2020.
Results Reference
result
PubMed Identifier
36836250
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):134. doi: 10.3390/jof9020134.
Results Reference
result

Learn more about this trial

ATCF (Azole Therapy in Cystic Fibrosis)

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