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ATCF (Azole Therapy in Cystic Fibrosis) (ATCF)

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ClinicalTrials.gov Identifier: NCT01576315
Recruitment Status : Completed
First Posted : April 12, 2012
Last Update Posted : April 12, 2016
Sponsor:
Information provided by (Responsible Party):
Rennes University Hospital

Study Description
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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.

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

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy of Itraconazole and of Voriconazole in Patients With Cystic Fibrosis and Presenting With Persistent Positive Sputums for Aspergillus.
Study Start Date : June 2014
Actual Primary Completion Date : October 2015
Actual Study Completion Date : November 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arms and Interventions
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Arm Intervention/treatment
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.


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]
    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 :
  1. plasma concentrations of antifungal agents [ Time Frame: at 2 weeks after initiation of therapy ]
    measurement of plasma concentrations of antifungal agents and testing at 4 weeks in case of dose adjustment.

  2. safety of AFs including measurement of hepatic transaminases [ Time Frame: at 2 weeks after initiation of therapy ]
    safety of AFs including measurement of hepatic transaminases

  3. number of courses of steroids and antibiotics recording [ Time Frame: at 2 weeks after initiation of therapy ]
    number of courses of steroids and antibiotics

  4. quality of life [ Time Frame: at 4, 8, 16 and 24 weeks after initiation of therapy ]
    quality of life self-questionnaire scores, dyspnoea scale scores, 6 minute walking test, FEV1 value, and number of courses of steroids and antibiotics

  5. laboratory test indicators [ Time Frame: at 4, 8, 16 and 24 weeks after initiation of therapy ]
    course of different laboratory test indicators (sputum culture and PCR, IgG, total and specific IgE, eosinophilia)

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

  7. mycological failures [ Time Frame: after 1 month ]
    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)

  8. number of adverse events recording [ Time Frame: at 2 weeks after initiation of therapy ]
    number of adverse events recording


Eligibility Criteria
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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01576315


Locations
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France
CRCM Adulte et Pédiatrie - Hôpital Nord
Amiens, France, 80054
CRCM adulte - Centre Robert Debré
Angers, France, 49033
Pediatry - Centre Robert Debré
Angers, France, 49033
Pediatric penumologic - Groupe hospitalier de Pellegrin
Bordeaux, France, 33000
Pneumology pediatric - Hôpital Femme-Mère-Enfants
Bron, France, 69500
CRCM - Pediatry - CHI Créteil
Créteil, France, 94000
Service de Pneumologie-Immuno-Allergologie / Hôpital Calmette
Lille, France, 59037
Hôpital Nord - Pneumology
Marseille, France, 13015
Pneumologie Infantile - Hôpital des enfants
Nancy, France, 54577
CRCM - Hôpital Sud
Rennes, France, 35000
Pneumology - Hôpital Pontchaillou
Rennes, France, 35000
CRCM Pédiatrique - Hôpital de Hautepierre
Strasbourg, France, 67098
Pédiatrie - Pneumologie, Allergologie - Hôpital des enfants
Toulouse, France, 31059
Pneumology - CH Bretagne-Atlantique
Vannes, France, 56017
United Kingdom
Manchester Adult Cystic Fibrosis Centre - University Hospital of South Manchester
Manchester, United Kingdom, M23 9LT
Sponsors and Collaborators
Rennes University Hospital
Investigators
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Principal Investigator: Jean-Pierre Gangneux, MD, PhD Service de parasito-mycologie - Rennes University Hospital
More Information
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Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT01576315    
Other Study ID Numbers: 2011-005799-41
First Posted: April 12, 2012    Key Record Dates
Last Update Posted: April 12, 2016
Last Verified: April 2016
Keywords provided by Rennes University Hospital:
cystic fibrosis
Aspergillus
itraconazole
voriconazole
Additional relevant MeSH terms:
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Aspergillosis
Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Mycoses
Bacterial Infections and Mycoses
Infections
 Itraconazole
Voriconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors