Bronchiectasis, Fungal Infection of Upper Respiratory Tract
Conditions
Brief summary
The primary objective of this study is to evaluate the feasibility of itraconazole therapy in patients with bronchiectasis and airway mold. Feasibility will be assessed through recruitment success, treatment adherence, tolerability, and participant retention. The study will also explore the impact on respiratory symptoms and airway microbiome diversity.
Interventions
Subjects will receive oral itraconazole, 200 mg twice daily, for six weeks, based on prior dosing regimens for airway fungal disease.
Sponsors
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years seen at Mycobacterial and Bronchiectasis Clinic (MMBC) in Rochester * Diagnosis of bronchiectasis confirmed by MMBC provider and chest CT * Within the last 3 months - culture growth of a mold in high quantity ('many') or culture growth of at least two distinct mold species in any quantity * Not actively on antimicrobial therapy AND no current plan to initiate antimicrobial therapy at the time of enrollment, as determined by treating provider * Ability to produce spontaneous sputum at Visit 1.
Exclusion criteria
* Known diagnosis of allergic bronchopulmonary aspergillosis or invasive fungal disease * Use of the following medications: rifampin, rifabutin, phenobarbital, phenytoin, carbamazepine, dofetilide, quinidine, dronedarone, simvastatin, lovastatin, certain immunosuppressants (tacrolimus, cyclosporine, sirolimus, everolimus) and anticoagulants (rivaroxaban, apixaban, edoxaban, warfarin). * Abnormal baseline liver function tests (ALT, AST, alkaline phosphatase, or bilirubin \> upper limit of normal) * Prolonged QTc interval on baseline ECG (\>460 ms in females or \>450 ms in males) * History of congestive heart failure (black box warning), known cardiomyopathy, or arrhythmias * Pregnancy or lactation * Known hypersensitivity or contraindication to azole antifungal therapy * Prior use of systemic antifungals within the past 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants who complete treatment without adverse effects | 2 years | Tolerability will be evaluated as the proportion of participants who complete the 6-week course without discontinuation due to adverse effects, with a target benchmark of ≥ 70%. |
| Proportion of patients retained for complete study | 2 years | Retention will be defined as the proportion of participants completing all scheduled study visits (baseline, day 7 and end of treatment), with a goal of ≥ 80% retention. |
| Proportion of eligible patients who consent and enroll | 2 years | Recruitment will be measured as the proportion of eligible patients who consent and enroll out of patients screened, reported as a percentage, with a benchmark of \>60%. |
| Number of patients to achieve successful medication adherence | 2 years | Adherence will be assessed through pill counts with successful adherence defined as ≥ 70% of doses taken and achieving a therapeutic trough level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants meeting hepatic safety discontinuation criteria | Baseline, 1 week | Hepatic safety will be monitored with serial hepatic function panels obtained at baseline, day 7, with the endpoint defined as the number of participants meeting discontinuation criteria: total bilirubin more than 2 times the ULN according to Mayo laboratory reference, ALT more than two times the ULN, AST more than two times the ULN, or ALP greater than 250 U/L. |
| Number of participants with a QTc interval greater than 500 ms | Baseline, 1 week | Cardiac safety will be assessed by obtaining an ECG on day 7, with the endpoint defined as the proportion of participants with a QTc interval greater than 500 ms. |
Countries
United States
Contacts
CONTACTPulmonary Clinical Research Office
CONTACTJennifer McNamara, BS
PRINCIPAL_INVESTIGATORAmjad Kanj, MD
Mayo Clinic
Outcome results
None listed