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

Bronchiectasis Clinical Trial

— BAIT  

Official title:

A Randomized Controlled Trial to 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06160713
• Other study ID #: Study 1291
• Status: Recruiting
• Phase: Phase 3
• Start date: December 1, 2023
• Est. completion date: January 31, 2026

Study information

• Verified date: December 2023
• Source: Postgraduate Institute of Medical Education and Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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?

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: January 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria: adults subjects (=13 years) with non-cystic fibrosis bronchiectasis fulfilling all the following criteria: • bronchiectasis on thin-section computed tomography (CT)

• 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

Related Conditions & MeSH terms

• Aspergillosis
• Bronchiectasis
• Bronchiectasis Adult

Intervention

Drug:
• Itraconazole 65 MG
Two capsules of suba-itraconazole 65 mg twice daily for 6 months

Other:
• Standard care
Standard care for bronchiectasis

Locations

Country	Name	City	State
India	Chest clinic	Chandigarh

Sponsors (1)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	frequency of bronchiectasis exacerbations during the study period	An exacerbation will be defined as clinical deterioration for at least 48 hours and the presence of three or more of the following six features: (1) increase in cough; (2) sputum volume/consistency; (3) sputum purulence; (4) breathlessness or exercise intolerance; (5) fatigue, malaise, or fever; (6) hemoptysis; and change of bronchiectasis treatment by a physician	(12 months [6 months each of intervention and observation])
Secondary	time to first exacerbation	Time taken for the first exacerbation	12 months
Secondary	change in the spirometric lung function (FVC)	Spirometry will be done to measure FVC	12 months
Secondary	change in the spirometric lung function ( FEV1)	Spirometry will be done to measure FEV1	12 months
Secondary	Change in 6 minute walk distance	6 minute walk test will be done at baseline and at treatment completion	6 months
Secondary	Adverse events	Adverse events during therapy will be assessed	6 months
Secondary	change in the quality of life assessed by bronchiectasis health questionnaire	We will use BHQ at baseline and 6 months	6 months