ATCF (Azole Therapy in Cystic Fibrosis)

This study is currently recruiting participants.
Verified December 2013 by Rennes University Hospital
Sponsor:
Information provided by (Responsible Party):
Rennes University Hospital
ClinicalTrials.gov Identifier:
NCT01576315
First received: March 29, 2012
Last updated: December 24, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Cystic Fibrosis
Aspergillus Infections
Drug: Itraconazole/voriconazole
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: ATCF (Azole Therapy in Cystic Fibrosis) Efficacy of Itraconazole and of Voriconazole in Patients With Cystic Fibrosis.

Resource links provided by NLM:


Further study details as provided by Rennes University Hospital:

Primary Outcome Measures:
  • Change in percentage of patients with a negativisation of sputum cultures in 2 successive samples [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 2 weeks after initiation of therapy ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 2 weeks after initiation of therapy ] [ Designated as safety issue: No ]
    safety of AFs including measurement of hepatic transaminases

  • number of courses of steroids and antibiotics recording [ Time Frame: at 2 weeks after initiation of therapy ] [ Designated as safety issue: No ]
    number of courses of steroids and antibiotics

  • quality of life [ Time Frame: at 4, 8, 16 and 24 weeks after initiation of therapy ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 4, 8, 16 and 24 weeks after initiation of therapy ] [ Designated as safety issue: No ]
    course of different laboratory test indicators (sputum culture and PCR, IgG, total and specific IgE, eosinophilia)

  • safety profiles of the antifungal agents [ Time Frame: at 4, 8, 16 and 24 weeks after initiation of therapy ] [ Designated as safety issue: Yes ]
    safety profiles of the antifungal agents : impact of anti-fungal treatments on lung and systemic inflammation

  • mycological failures [ Time Frame: after 1 month ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 2 weeks after initiation of therapy ] [ Designated as safety issue: No ]
    number of adverse events recording


Estimated Enrollment: 150
Study Start Date: September 2012
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
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.
Other Name: Non applicable.
Experimental: 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
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.
Other Name: Non applicable.

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.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01576315

Contacts
Contact: Jean-Pierre Gangneux, MD, PhD +33-223-234-490 jean-pierre.gangneux@chu-rennes.fr

Locations
France
CRCM Adulte et Pédiatrie - Hôpital Nord Recruiting
Amiens, France, 80054
Principal Investigator: Jean-Claude PAUTARD, MD         
CRCM adulte - Centre Robert Debré Recruiting
Angers, France, 49033
Principal Investigator: Thierry URBAN, MD         
Pediatry - Centre Robert Debré Recruiting
Angers, France, 49033
Principal Investigator: Jean-Louis GINIES, MD, PhD         
Pediatric penumologic - Groupe hospitalier de Pellegrin Recruiting
Bordeaux, France, 33000
Principal Investigator: Michael FAYON, MD         
Pneumology pediatric - Hôpital Femme-Mère-Enfants Recruiting
Bron, France, 69500
Principal Investigator: Stéphanie VRIELYNCK, MD         
CRCM - Pediatry - CHI Créteil Recruiting
Créteil, France, 94000
Principal Investigator: Natascha REMUS, MD         
Service de Pneumologie-Immuno-Allergologie / Hôpital Calmette Recruiting
Lille, France, 59037
Principal Investigator: Anne PREVOTAT, MD         
Hôpital Nord - Pneumology Recruiting
Marseille, France, 13015
Contact: Martine REYNAUD-GAUBERT, MD, PhD         
Principal Investigator: Martine REYNAUD-GAUBERT, MD, PhD         
Pneumologie Infantile - Hôpital des enfants Recruiting
Nancy, France, 54577
Principal Investigator: Jocelyne DERELLE, MD         
Pneumology - Hôpital Pontchaillou Recruiting
Rennes, France, 35000
Principal Investigator: Chantal BELLEGUIC, MD         
CRCM - Hôpital Sud Not yet recruiting
Rennes, France, 35000
Principal Investigator: Michel ROUSSEY, MD, PhD         
CRCM Pédiatrique - Hôpital de Hautepierre Recruiting
Strasbourg, France, 67098
Principal Investigator: Laurent Weiss, MD         
Pédiatrie - Pneumologie, Allergologie - Hôpital des enfants Recruiting
Toulouse, France, 31059
Principal Investigator: François BREMONT, MD         
Pneumology - CH Bretagne-Atlantique Recruiting
Vannes, France, 56017
Principal Investigator: Marie-Laure UFFREDI, MD         
United Kingdom
Manchester Adult Cystic Fibrosis Centre - University Hospital of South Manchester Recruiting
Manchester, United Kingdom, M23 9LT
Principal Investigator: Alex HORSLEY, MD         
Sponsors and Collaborators
Rennes University Hospital
Investigators
Principal Investigator: Jean-Pierre Gangneux, MD, PhD Service de parasito-mycologie - Rennes University Hospital
  More Information

No publications provided

Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT01576315     History of Changes
Other Study ID Numbers: 2011-005799-41
Study First Received: March 29, 2012
Last Updated: December 24, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Rennes University Hospital:
cystic fibrosis
Aspergillus
itraconazole
voriconazole

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Aspergillosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Mycoses
Itraconazole
Voriconazole
Hydroxyitraconazole
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014