Compare Oral Itraconazole and Standard Care Versus Standard Care Alone in Patients With Non-cystic Fibrosis Related Bronchiectasis With Chronic Aspergillus Infection in Reducing Bronchiectasis Exacerbations

NCT ID: NCT06160713

Last Updated: 2023-12-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-01
• Study Completion Date: 2026-01-31

Brief Summary

There is an intricate link between bronchiectasis and fungi. Patients with cystic fibrosis frequently manifest fungal sensitization and fungal colonization with Aspergillus fumigatus.6 Aspergillus species also has a cause-and-effect relationship with non-CF (cystic fibrosis) bronchiectasis.7, 8 In allergic bronchopulmonary aspergillosis (ABPA), Aspergillus is the cause of bronchiectasis. In contrast, in other causes of bronchiectasis, A fumigatus can theoretically promote allergic response, which may result in poor lung function, increase the risk of exacerbations, and even cause ABPA over time.9, 10 In a recent study, we found an overall prevalence of Aspergillus sensitization of 29.5% and the prevalence of chronic aspergillus infection was 76%.11 The prevalence of chronic aspergillus colonization in non-(tuberculosis) TB-non-CF fibrosis was 47.5% (49/103).11 By mechanism similar to chronic bacterial colonization, chronic aspergillus infection or aspergillus sensitization can increase the risk of bronchiectasis exacerbation. Therefore, eradication of A. fumigatus from the airways of patients with bronchiectasis would decrease the future risk of a bronchiectasis exacerbation. Notably, in ABPA, use of itraconazole and voriconazole reduce the exacerbations by reducing the fungal burden in the airways.12, 13 In this randomized trial, we will investigate whether treatment with oral itraconazole for six months would reduce the future risk of bronchiectasis exacerbation in patients with non-CF-non-ABPA bronchiectasis.

Detailed Description

Bronchiectasis is a chronic lung disease due to irreversible and abnormal dilatation of the bronchi. Bronchiectasis manifest with chronic cough, expectoration, hemoptysis, dyspnea, and others. Bronchiectasis can be broadly classified as genetic (cystic fibrosis [CF], ciliary dyskinesia and others) or acquired (post-infective, tuberculosis (TB), allergic bronchopulmonary aspergillosis [ABPA] and others).1 The natural course of bronchiectasis is associated with recurrent exacerbations that cause further damage and disease progression.2 Most exacerbations are caused by viral or bacterial infections, inflammation and external environment factors. Chronic bacterial infections increase the risk of bronchiectasis exacerbation.2 In a multicentric European study chronic infection with Pseudomonas aeruginosa was associated with an increased risk of exacerbation.3 Notably, change in the interaction between the bacterial microbiome by external inciting events (viral infection or air pollution) increases exacerbation risk.4 Similarly, viral infections by increasing the systemic and airway inflammation induce a bronchiectasis exacerbation.5 Airway inflammation both neutrophilic and eosinophilic are also important causes of bronchiectasis exacerbations.2 Most previous studies in non-CF bronchiectasis have not investigated the role of fungal sensitization or chronic fungal infection in causing bronchiectasis exacerbation.

There is an intricate link between bronchiectasis and fungi. Patients with cystic fibrosis frequently manifest fungal sensitization and fungal colonization with Aspergillus fumigatus.6 Aspergillus species also has a cause-and-effect relationship with non-CF bronchiectasis.7, 8 In ABPA, Aspergillus is the cause of bronchiectasis. In contrast, in other causes of bronchiectasis, A fumigatus can theoretically promote allergic response, which may result in poor lung function, increase the risk of exacerbations, and even cause ABPA over time.9, 10 In a recent study, we found an overall prevalence of Aspergillus sensitization of 29.5% and the prevalence of chronic aspergillus infection was 76%.11 The prevalence of chronic aspergillus colonization in non-TB-non-CF fibrosis was 47.5% (49/103).11 By mechanism similar to chronic bacterial colonization, chronic aspergillus infection or aspergillus sensitization can increase the risk of bronchiectasis exacerbation. Therefore, eradication of A. fumigatus from the airways of patients with bronchiectasis would decrease the future risk of a bronchiectasis exacerbation. Notably, in ABPA, use of itraconazole and voriconazole reduce the exacerbations by reducing the fungal burden in the airways.12, 13 In this randomized trial, we will investigate whether treatment with oral itraconazole for six months would reduce the future risk of bronchiectasis exacerbation in patients with non-CF-non-ABPA bronchiectasis.

Study question: Does oral itraconazole for six months reduce the bronchiectasis exacerbation in patients with non-cystic fibrosis bronchiectasis?

Conditions

Bronchiectasis; Bronchiectasis Adult

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard care

Standard care of bronchiectasis

Group Type: ACTIVE_COMPARATOR

Standard care

Intervention Type: OTHER

Standard care for bronchiectasis

Itraconazole arm

Supra-bioavailable- Itraconazole capsule 65 mg

Group Type: EXPERIMENTAL

Itraconazole 65 MG

Intervention Type: DRUG

Two capsules of suba-itraconazole 65 mg twice daily for 6 months

Standard care

Intervention Type: OTHER

Standard care for bronchiectasis

Interventions

Itraconazole 65 MG

Two capsules of suba-itraconazole 65 mg twice daily for 6 months

Intervention Type: DRUG

Standard care

Standard care for bronchiectasis

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• chronic aspergillus infection defined by the presence of A.fumigatus-specific IgG ≥40 mgA/L
• clinically stable for at least three months prior to study inclusion

Exclusion Criteria

We will exclude subjects with any of the following:

• allergic bronchopulmonary aspergillosis as the cause of underlying bronchiectasis
• cystic fibrosis
• post-tuberculosis bronchiectasis
• severe asthma
• current smokers
• active bacterial, mycobacterial (atypical or typical), or fungal (aspergillosis or mucormycosis) infections
• use of systemic antifungal drugs in past 3 months
• previous documented intolerance to itraconazole
• pregnancy
• failure to provide informed consent

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Post Graduate Institute of Medical Education and Research, Chandigarh

OTHER

Sponsor Role: lead

Responsible Party

Inderpaul singh

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Chest clinic

Chandigarh, , India

Site Status: RECRUITING

Countries

India

Facility Contacts

Inderpaul S Sehgal, MD,DM

Role: primary

inderpgi@outlook.com

+91-172275 ext. 6823

Other Identifiers

Study 1291

Identifier Type: -

Identifier Source: org_study_id