Cystic FibrosisPhase 2ATCFNCT01576315
ATCF (Azole Therapy in Cystic Fibrosis)
A Phase 2 study testing Itraconazole/voriconazole in people with Cystic Fibrosis and Aspergillus Infections, run by Rennes University Hospital at 15 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Cystic Fibrosis, Aspergillus Infections
- What is being tested?
- Itraconazole/voriconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 15 sitesin 2 countries
- Study dates
- Jun 2014to Nov 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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,
Show all 12Show fewer
- 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.
Trial locations and contacts
15 sites in 2 countries.
15 sites in 2 countries
France14 sites
CRCM Adulte et Pédiatrie - Hôpital Nord
Amiens, 80054
CRCM adulte - Centre Robert Debré
Angers, 49033
Pediatry - Centre Robert Debré
Angers, 49033
Pediatric penumologic - Groupe hospitalier de Pellegrin
Bordeaux, 33000
Pneumology pediatric - Hôpital Femme-Mère-Enfants
Bron, 69500
CRCM - Pediatry - CHI Créteil
Créteil, 94000
Service de Pneumologie-Immuno-Allergologie / Hôpital Calmette
Lille, 59037
Hôpital Nord - Pneumology
Marseille, 13015
Pneumologie Infantile - Hôpital des enfants
Nancy, 54577
CRCM - Hôpital Sud
Rennes, 35000
Pneumology - Hôpital Pontchaillou
Rennes, 35000
CRCM Pédiatrique - Hôpital de Hautepierre
Strasbourg, 67098
Pédiatrie - Pneumologie, Allergologie - Hôpital des enfants
Toulouse, 31059
Pneumology - CH Bretagne-Atlantique
Vannes, 56017
United Kingdom1 site
Manchester Adult Cystic Fibrosis Centre - University Hospital of South Manchester
Manchester, M23 9LT
About this study
Official title: Efficacy of Itraconazole and of Voriconazole in Patients With Cystic Fibrosis and Presenting With Persistent Positive Sputums for Aspergillus.
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.
Read the 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.
- Conditions
- Cystic Fibrosis, Aspergillus Infections
- Being tested
- Itraconazole/voriconazole
- Keywords
- cystic fibrosis, Aspergillus, itraconazole, voriconazole
- Medical subject headings
- Cystic Fibrosis, Aspergillosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Itraconazole/voriconazoleDrug
Also called Non applicable.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Itraconazole/voriconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
measurement of plasma concentrations of antifungal agents and testing at 4 weeks in case of dose adjustment.
Measured: at 2 weeks after initiation of therapy
safety of AFs including measurement of hepatic transaminases
safety of AFs including measurement of hepatic transaminases
Measured: at 2 weeks after initiation of therapy
number of courses of steroids and antibiotics recording
number of courses of steroids and antibiotics
Measured: at 2 weeks after initiation of therapy
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
Measured: at 4, 8, 16 and 24 weeks after initiation of therapy
laboratory test indicators
course of different laboratory test indicators (sputum culture and PCR, IgG, total and specific IgE, eosinophilia)
Measured: at 4, 8, 16 and 24 weeks after initiation of therapy
safety profiles of the antifungal agents
safety profiles of the antifungal agents : impact of anti-fungal treatments on lung and systemic inflammation
Measured: at 4, 8, 16 and 24 weeks after initiation of therapy
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)
Measured: after 1 month
number of adverse events recording
number of adverse events recording
Measured: at 2 weeks after initiation of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2012 (estimated)
- Study startJun 2014
- Primary completionOct 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Rennes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean-Pierre Gangneux, MD, PhD, Principal investigator, Service de parasito-mycologie - Rennes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01576315
- Sponsor's protocol ID
- 2011-005799-41
- Acronym
- ATCF
- Status last verified
- May 2023
- First submitted
- 29 Mar 2012
- Last updated
- 24 May 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 35822920Guegan 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.
PubMed 33680981Guegan 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.
PubMed 36836250
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Itraconazole and of Voriconazole in Patients With Cystic Fibrosis and Presenting With Persistent Positive Sputums for Aspergillus.
- ClinicalTrials.gov ID
- NCT01576315
- Acronym / sponsor ID
- ATCF / 2011-005799-41
- Conditions
- Cystic Fibrosis, Aspergillus Infections
- Keywords
- cystic fibrosis, Aspergillus, itraconazole, voriconazole
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Study start
- Jun 2014
- Primary completion
- Oct 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 12 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| itraconazole | Experimental | Drug: Itraconazole/voriconazole* 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 | Experimental | Drug: Itraconazole/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 |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (12 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Itraconazole/voriconazoleAlso: Non applicable.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. | Drug | itraconazole, voriconazole |
Primary outcome
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
8 secondary outcomes
plasma concentrations of antifungal agents
Time frame: at 2 weeks after initiation of therapy
safety of AFs including measurement of hepatic transaminases
Time frame: at 2 weeks after initiation of therapy
number of courses of steroids and antibiotics recording
Time frame: at 2 weeks after initiation of therapy
quality of life
Time frame: at 4, 8, 16 and 24 weeks after initiation of therapy
laboratory test indicators
Time frame: at 4, 8, 16 and 24 weeks after initiation of therapy
safety profiles of the antifungal agents
Time frame: at 4, 8, 16 and 24 weeks after initiation of therapy
mycological failures
Time frame: after 1 month
number of adverse events recording
Time frame: at 2 weeks after initiation of therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2023.
- Results publication: PubMed 35822920Gangneux 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 publication: PubMed 33680981Guegan 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 publication: PubMed 36836250Guegan 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-Pierre Gangneux, MD, PhD principal investigator
Service de parasito-mycologie - Rennes University Hospital
15 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Itraconazole/voriconazole in people with Cystic Fibrosis and Aspergillus Infections, run by Rennes University Hospital at 15 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in France, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01576315, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2023.