Prospective validation and clinical evaluation of a new posaconazole dosingregimen for children and adolescents with cystic fibrosis and Aspergillus infection.
- Conditions
- Cystic Fibrosis and Aspergillus InfectionMedDRA version: 20.0Level: LLTClassification code 10003488Term: AspergillosisSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2019-004511-31-GB
- Lead Sponsor
- Bambino Gesù Children's Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- All
- Target Recruitment
- 135
Inclusion criteria for the screening phase:
1. Diagnosed with cystic fibrosis (genetic diagnosis and/or abnormal sweat test and clinical phenotype of lung disease)
2. Age = 8 yrs and < 18 yrs
3. Body weight = 20 kg
4. Able to produce a sputum sample (spontaneous or induced sputum)
5. Informed Consent given
Inclusion criteria for the intervention phase:
1. Diagnosed with cystic fibrosis (genetic diagnosis and/or abnormal sweat test and clinical phenotype of lung disease)
2. Age = 8 yrs and < 18 yrs
3. Body weight = 20 kg
4. Presence of Aspergillus infection as defined for this study
5. Clinically stable condition without a significant change in lung function (FEV1 +/- 10%) or significant worsening of respiratory symptoms over the previous month
6. Able to perform lung function test (FEV1%)
7. Able to produce a sputum sample (spontaneous or induced sputum)
8. Informed Consent given
9. If female and of childbearing age must be using highly effective contraception (and must agree to continue for 7 days after the last dose of investigational medicinal product [IMP]) [1[
Footnote: [1] Highly effective contraception is defined as one of the following: combined (estrogen and progestogen containing) hormonal
contraception associated with inhibition of ovulation (oral, injectable or transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable); intrauterine device (IUD); intrauterine hormone-releasing system ( IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence (defined as refraining from heterosexual intercourse when it is in line with the preferred and usual lifestyle of the subject)
Are the trial subjects under 18? yes
Number of subjects for this age range: 135
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
Exclusion criteria for the screening phase:
1. Non-CF lung disorder
2. Age < 8 yrs of age or = 18 yrs of age
3. Body weight < 20 kg
4. Not able to provide sputum sample
5. Informed Consent not given
Exclusion criteria for the intervention phase:
1. Non-CF lung disorder
2. Age < 8 yrs or = 18 yrs
3. Body weight < 20 kg
4. Not able to perform lung function test (FEV1%)
5. Unable to produce a sputum sample (spontaneous or induced sputum)
6. Clinically unstable condition with significant change in lung function or significant worsening of respiratory symptoms
7. Unable to tolerate oral medication
8. Known hypersensitivity to itraconazole or posaconazole, or it’s excipients.
9. On active transplant list or transplant recipient
10. Azole resistant Aspergillus sp. cultured
11. Patients receiving terfenadine, ergot alkaloids, astemizole, cisapride, pimozide, halofantrine, quinidine, or HMG-CoA reductase inhibitors metabolised through CYP3A4 (eg. simvastatin, lovastatin, and atorvastatin)
12. Patients receiving omalizumab
13. Received systemic mould-active antifungals in the last month
14. Shortened or elongated QT interval
15. Cardiac failure
16. ALT = 200 U/L
17. AST = 225 U/L
18. Alkaline phosphatase = 460 U/L
19. Bilirubin = 50 umol/L
20. eGFR < 20 ml/min/1.73 m2 (calculated with the Schwartz formula)
21. Patients with known glucose-galactose malabsorption problems
22. Pregnancy [2] or breastfeeding
23. Females of childbearing age who do not intend to use contraception measures.
24. Informed Consent not given
Footnote: [2] For females of child bearing age this must be confirmed by a pregnancy test within 10 days prior to randomizatio
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method